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Volume 0,Issue 2,2025 Table of Contents
2025, 32(2):127-139.
DOI: 10.3872/j.issn.1007-385X.2025.02.001
Abstract:
[Abstract] Hematologic malignancies are a severe threat to human health. CAR-T cell therapy, as a highly effective treatment for hematologic malignancies, has become one of the fastest developing cancer immunotherapies in recent years. To obtain highly effective and low-toxicity CAR-T cells, through continuous development and exploration, CAR-T cell therapy has achieved a series of significant breakthroughs in treating hematologic malignancies, including humanized CAR-T cell technology, dual-target and multitarget CAR-T cell technology, universal CAR-T cell technology, and CAR-T cell combination strategy technology. Humanized CAR-T cell technology reduces immunogenicity through humanized modification. Dual-target and multi-target CAR-T cell technology recognizes two or more tumor antigens, minimizes antigen escape and enhance efficacy. Universal CAR-T cell technology solves problems such as high cost and accessibility issues. The CAR-T cell combination strategy technology effectively deals with CAR-T recurrence and enhances efficacy and safety by combining different treatment methods. Although CAR-T cell therapy has achieved significant breakthroughs in the treatment of hematologic malignancies, it still faces challenges such as drug resistance, antigen escape, cytotoxicity, and posttreatment recurrence. This review presents the significant breakthroughs, existing problems, and solutions for CAR-T cell precise therapy for hematological malignancies.
[Abstract] Hematologic malignancies are a severe threat to human health. CAR-T cell therapy, as a highly effective treatment for hematologic malignancies, has become one of the fastest developing cancer immunotherapies in recent years. To obtain highly effective and low-toxicity CAR-T cells, through continuous development and exploration, CAR-T cell therapy has achieved a series of significant breakthroughs in treating hematologic malignancies, including humanized CAR-T cell technology, dual-target and multitarget CAR-T cell technology, universal CAR-T cell technology, and CAR-T cell combination strategy technology. Humanized CAR-T cell technology reduces immunogenicity through humanized modification. Dual-target and multi-target CAR-T cell technology recognizes two or more tumor antigens, minimizes antigen escape and enhance efficacy. Universal CAR-T cell technology solves problems such as high cost and accessibility issues. The CAR-T cell combination strategy technology effectively deals with CAR-T recurrence and enhances efficacy and safety by combining different treatment methods. Although CAR-T cell therapy has achieved significant breakthroughs in the treatment of hematologic malignancies, it still faces challenges such as drug resistance, antigen escape, cytotoxicity, and posttreatment recurrence. This review presents the significant breakthroughs, existing problems, and solutions for CAR-T cell precise therapy for hematological malignancies.
PAN Yingjie
,
SUN Shan
,
YANG Hang
,
TAN Jinsong
,
CHEN Qiaoling
,
ZHAO Quanneng
,
YANG Mi
,
LIU Kang
,
SONG Guiqin
2025, 32(2):140-150.
DOI: 10.3872/j.issn.1007-385X.2025.02.002
Abstract:
[Abstract] Objective: To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins (WTAP) on the cell biological properties of esophageal squamous cell carcinoma (ESCC) cells. Methods: 31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected. The esophageal cancer cells KYSE30, KYSE410, KYSE150, KYSE510, TE-1, and normal human esophageal epithelial cells HET-1A were routinely cultured. Transfection reagents were used to transfect si-NC, si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells. The cells were divided into si-NC, si-WTAP#1 and si-WTAP#2 groups. The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay. CCK-8 assay, clone formation assay, and scratch healing assay, Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation, migration, invasion and apoptosis. WB assay was used to detect the expressions of WTAP, MAP3K9, EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP; immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues, immunoprecipitation of methylated RNA (MeRIP)-qPCR assay to detect the level of MAP3K9 m6 A in ESCC cells, actinomycin D assay to detect the stability of mRNA of MAP3K9, and database data to analyze the expression, target genes, functional enrichment, and interacting RNA of WTAP. Results: WTAP was highly expressed in ESCC tissues and cells (P < 0.05 or P < 0.01 or P < 0.001) and correlated with the degree of differentiation (P < 0.01); the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells (P < 0.01 or P < 0.001); the knockdown of WTAP significantly inhibited the proliferation, migration and invasion of KYSE150 and KYSE510 cells (P < 0.05 or P < 0.01 or P < 0.001), and promoted the apoptosis of KYSE150 and KYSE510 cells (P < 0.05 or P < 0.01). Knockdown of WTAP resulted in a significant decrease in the m6 A level of MAP3K9 (P < 0.05), and its mRNA expression level and mRNA stability were both significantly reduced (P < 0.05). Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway; the expression levels of MAP3K9, p-ERK, N-cadherin, and MMP9 were significantly reduced (P < 0.05 or P < 0.01), and the expression level of E-cadherin was significantly elevated (P < 0.05 or P < 0.01) in the KYSE150 and KYSE510 cells after knockdown of WTAP. Conclusions: WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation. It promotes the stability of MAP3K9 mRNA through m6 A modification, activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.
[Abstract] Objective: To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins (WTAP) on the cell biological properties of esophageal squamous cell carcinoma (ESCC) cells. Methods: 31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected. The esophageal cancer cells KYSE30, KYSE410, KYSE150, KYSE510, TE-1, and normal human esophageal epithelial cells HET-1A were routinely cultured. Transfection reagents were used to transfect si-NC, si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells. The cells were divided into si-NC, si-WTAP#1 and si-WTAP#2 groups. The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay. CCK-8 assay, clone formation assay, and scratch healing assay, Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation, migration, invasion and apoptosis. WB assay was used to detect the expressions of WTAP, MAP3K9, EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP; immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues, immunoprecipitation of methylated RNA (MeRIP)-qPCR assay to detect the level of MAP3K9 m6 A in ESCC cells, actinomycin D assay to detect the stability of mRNA of MAP3K9, and database data to analyze the expression, target genes, functional enrichment, and interacting RNA of WTAP. Results: WTAP was highly expressed in ESCC tissues and cells (P < 0.05 or P < 0.01 or P < 0.001) and correlated with the degree of differentiation (P < 0.01); the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells (P < 0.01 or P < 0.001); the knockdown of WTAP significantly inhibited the proliferation, migration and invasion of KYSE150 and KYSE510 cells (P < 0.05 or P < 0.01 or P < 0.001), and promoted the apoptosis of KYSE150 and KYSE510 cells (P < 0.05 or P < 0.01). Knockdown of WTAP resulted in a significant decrease in the m6 A level of MAP3K9 (P < 0.05), and its mRNA expression level and mRNA stability were both significantly reduced (P < 0.05). Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway; the expression levels of MAP3K9, p-ERK, N-cadherin, and MMP9 were significantly reduced (P < 0.05 or P < 0.01), and the expression level of E-cadherin was significantly elevated (P < 0.05 or P < 0.01) in the KYSE150 and KYSE510 cells after knockdown of WTAP. Conclusions: WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation. It promotes the stability of MAP3K9 mRNA through m6 A modification, activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.
2025, 32(2):151-160.
DOI: 10.3872/j.issn.1007-385X.2025.02.003
Abstract:
[Abstract] Objective: To investigate the role of SiHa cell-derived exosomal hsa-miR-29c-3p in the angiogenesis of cervical cancer (CC). Methods: Cancer tissue specimens from 45 patients with cervical squamous cell carcinoma (CSCC) and normal cervical tissue specimens from 15 controls were collected from Department of Gynecology, Hengyang Central Hospital from January 2019 to December 2021. CSCC SiHa cells and human umbilical vein endothelial cells （HUVECs）were routinely cultured. miRNA-NC, hsa-miR-29c-3p, si-miRNA-NC, and si-hsa-miR-29c-3p were transfected into SiHa cells with Lipofectamine 2000, grouped as miRNA-NC group, hsa-miR-29c-3p group, si-miRNA-NC group and si-hsa-miR-29c-3p group, respectively. HUVECs were transfected with mimic-NC, miR-29c-3p-mimic, pCMV-NC, and pCMV-ATAD2B (ATPase family protein 2B with AAA domain) using Lipofectamine 2000, grouped as the mimic-NC group, miR-29c-3p-mimic group, pCMV-NC group, pCMV-ATAD2B group, and pCMV-ATAD2B + miR-29c-3p-mimic group. The expression of hsa-miR-29c-3p in CSCC tissues was detected by in situ hybridization (ISH), and CD31-positive blood vessels in CSCC tissues and xenograft tissues were detected by immunohistochemistry (IHC). Exosomes from SiHa and C33a cells were isolated and characterized using transmission electron microscopy (TEM) and western blotting (WB). The uptake of exosomes by HUVECs was examined. The expression of hsa-miR-29c-3p and ATAD2B mRNA in SiHa and C33a cells, as well as in their derived exosomes, was detected using qPCR. Tube-forming assay, Transwell assay, and scratch healing assay were performed to detect the effect of exosomes on the ability of HUVEC migration and tube formation. Dual luciferase reporter gene assay verified the interaction between hsa-miR-29c-3p and ATAD2B. Xenograft experiments examined the effects of SiHa cell-derived exosomes on transplanted tumor growth and angiogenesis in each group. Results: hsa-miR-29c-3p was highly expressed in CSCC tissues and was positively correlated with microvessel density (MVD) (all P < 0.05). Exosomes derived from SiHa and C33a cells exhibited typical exosomal morphology and protein expression patterns. Exosomal hsa-miR-29c-3p from SiHa and C33a cells were efficiently taken up by HUVECs in vitro. The SiHa cell-derived exosomal hsa-miR-29c-3p promoted not only the tube-forming and migration of HUVECs in vitro but also the xenograft growth and angiogenesis in vivo (all P < 0.05). hsa-miR-29c-3p directly targeted ATAD2B and regulated its expression (P < 0.05). Overexpression of ATAD2B reversed the promotive effect of hsa-miR-29c-3p on tube-formation, migration, and scratch-healing in HUVECs (all P < 0.05). Conclusion: SiHa cell-derived exosomal hsa-miR-29c-3p regulates angiogenesis in CSCC tissues by targeting ATAD2B. Exosomal hsa-miR-29c-3p may be a potential diagnostic marker and therapeutic target for CC diagnosis and treatment.
[Abstract] Objective: To investigate the role of SiHa cell-derived exosomal hsa-miR-29c-3p in the angiogenesis of cervical cancer (CC). Methods: Cancer tissue specimens from 45 patients with cervical squamous cell carcinoma (CSCC) and normal cervical tissue specimens from 15 controls were collected from Department of Gynecology, Hengyang Central Hospital from January 2019 to December 2021. CSCC SiHa cells and human umbilical vein endothelial cells （HUVECs）were routinely cultured. miRNA-NC, hsa-miR-29c-3p, si-miRNA-NC, and si-hsa-miR-29c-3p were transfected into SiHa cells with Lipofectamine 2000, grouped as miRNA-NC group, hsa-miR-29c-3p group, si-miRNA-NC group and si-hsa-miR-29c-3p group, respectively. HUVECs were transfected with mimic-NC, miR-29c-3p-mimic, pCMV-NC, and pCMV-ATAD2B (ATPase family protein 2B with AAA domain) using Lipofectamine 2000, grouped as the mimic-NC group, miR-29c-3p-mimic group, pCMV-NC group, pCMV-ATAD2B group, and pCMV-ATAD2B + miR-29c-3p-mimic group. The expression of hsa-miR-29c-3p in CSCC tissues was detected by in situ hybridization (ISH), and CD31-positive blood vessels in CSCC tissues and xenograft tissues were detected by immunohistochemistry (IHC). Exosomes from SiHa and C33a cells were isolated and characterized using transmission electron microscopy (TEM) and western blotting (WB). The uptake of exosomes by HUVECs was examined. The expression of hsa-miR-29c-3p and ATAD2B mRNA in SiHa and C33a cells, as well as in their derived exosomes, was detected using qPCR. Tube-forming assay, Transwell assay, and scratch healing assay were performed to detect the effect of exosomes on the ability of HUVEC migration and tube formation. Dual luciferase reporter gene assay verified the interaction between hsa-miR-29c-3p and ATAD2B. Xenograft experiments examined the effects of SiHa cell-derived exosomes on transplanted tumor growth and angiogenesis in each group. Results: hsa-miR-29c-3p was highly expressed in CSCC tissues and was positively correlated with microvessel density (MVD) (all P < 0.05). Exosomes derived from SiHa and C33a cells exhibited typical exosomal morphology and protein expression patterns. Exosomal hsa-miR-29c-3p from SiHa and C33a cells were efficiently taken up by HUVECs in vitro. The SiHa cell-derived exosomal hsa-miR-29c-3p promoted not only the tube-forming and migration of HUVECs in vitro but also the xenograft growth and angiogenesis in vivo (all P < 0.05). hsa-miR-29c-3p directly targeted ATAD2B and regulated its expression (P < 0.05). Overexpression of ATAD2B reversed the promotive effect of hsa-miR-29c-3p on tube-formation, migration, and scratch-healing in HUVECs (all P < 0.05). Conclusion: SiHa cell-derived exosomal hsa-miR-29c-3p regulates angiogenesis in CSCC tissues by targeting ATAD2B. Exosomal hsa-miR-29c-3p may be a potential diagnostic marker and therapeutic target for CC diagnosis and treatment.
2025, 32(2):161-168.
DOI: 10.3872/j.issn.1007-385X.2025.02.004
Abstract:
[Abstract] Objective: To explore the mechanism of lncRNA FOXD2-AS1 regulating the expression of LATS1 via EZH2 to affect the proliferation and migration of clear cell renal cell carcinoma (ccRCC) cells. Methods: The GEPIA 2 online tool was used to analyze the expression levels of FOXD2-AS1 in ccRCC tissues from the Cancer Genome Atlas (TCGA) database, and their correlation with patients’ overall survival rates was evaluated. Quantitative PCR (qPCR) was performed to analyze the expressions of FOXD2-AS1 in renal cancer cells and 26 clinically collected ccRCC tissue samples. CCK-8 cell proliferation assay and transwell chamber migration assay were employed to observe the effects of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. qPCR and Western blot analysis were utilized to assess the impact of FOXD2-AS1 knockdown on the expression of LATS1. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were performed to analyze the interaction between FOXD2-AS1, EZH2, and LATS1. Results: The GEPIA 2 software analysis revealed that FOXD2-AS1 was significantly upregulated in ccRCC tissues (P < 0.01) and patients with high FOXD2-AS1 expression exhibited lower overall survival rates (P < 0.05). The qPCR analysis results showed that FOXD2-AS1 was significantly upregulated in 26 samples of ccRCC tissues compared with adjacent normal kidney tissues (P < 0.01). Compared with immortalized renal tubular epithelial cell line HK-2, the expression of FOXD2-AS1was significantly elevated in three types of renal cancer cell lines (786-O, ACHN and SN12-PM6) (P < 0.01). Knockdown of FOXD2-AS1 expression significantly decreased the proliferation and migration abilities of renal cancer cells (P < 0.05), and markedly increased the mRNA and protein expression levels of LATS1 (all P < 0.01). RIP and ChIP assays confirmed that FOXD2-AS1 can bind and recruit EZH2 to the promoter region of LATS1 to exert its effect. Salvage experiments demonstrated that knocking down LATS1 or overexpressing EZH2 partially reversed the inhibitory effect of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. Conclusion: FOXD2-AS1 is highly expressed in ccRCC, and it negatively regulates the expression of LATS1 by recruiting EZH2 to the promoter region of the LATS1 gene, thereby facilitating the proliferation and migration of renal cancer cells.
[Abstract] Objective: To explore the mechanism of lncRNA FOXD2-AS1 regulating the expression of LATS1 via EZH2 to affect the proliferation and migration of clear cell renal cell carcinoma (ccRCC) cells. Methods: The GEPIA 2 online tool was used to analyze the expression levels of FOXD2-AS1 in ccRCC tissues from the Cancer Genome Atlas (TCGA) database, and their correlation with patients’ overall survival rates was evaluated. Quantitative PCR (qPCR) was performed to analyze the expressions of FOXD2-AS1 in renal cancer cells and 26 clinically collected ccRCC tissue samples. CCK-8 cell proliferation assay and transwell chamber migration assay were employed to observe the effects of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. qPCR and Western blot analysis were utilized to assess the impact of FOXD2-AS1 knockdown on the expression of LATS1. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were performed to analyze the interaction between FOXD2-AS1, EZH2, and LATS1. Results: The GEPIA 2 software analysis revealed that FOXD2-AS1 was significantly upregulated in ccRCC tissues (P < 0.01) and patients with high FOXD2-AS1 expression exhibited lower overall survival rates (P < 0.05). The qPCR analysis results showed that FOXD2-AS1 was significantly upregulated in 26 samples of ccRCC tissues compared with adjacent normal kidney tissues (P < 0.01). Compared with immortalized renal tubular epithelial cell line HK-2, the expression of FOXD2-AS1was significantly elevated in three types of renal cancer cell lines (786-O, ACHN and SN12-PM6) (P < 0.01). Knockdown of FOXD2-AS1 expression significantly decreased the proliferation and migration abilities of renal cancer cells (P < 0.05), and markedly increased the mRNA and protein expression levels of LATS1 (all P < 0.01). RIP and ChIP assays confirmed that FOXD2-AS1 can bind and recruit EZH2 to the promoter region of LATS1 to exert its effect. Salvage experiments demonstrated that knocking down LATS1 or overexpressing EZH2 partially reversed the inhibitory effect of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. Conclusion: FOXD2-AS1 is highly expressed in ccRCC, and it negatively regulates the expression of LATS1 by recruiting EZH2 to the promoter region of the LATS1 gene, thereby facilitating the proliferation and migration of renal cancer cells.
2025, 32(2):169-175.
DOI: 10.3872/j.issn.1007-385X.2025.02.005
Abstract:
[Abstract] Objective: To explore the expression of chemokine ligand 1 (CCL1) in oral squamous cell carcinoma (OSCC) and its effect on the proliferation, migration and invasion of human oral tongue squamous cell carcinoma cells (HSC-4). Methods: 28 OSCC tissue samples and clinical characteristic data of patients were collected at the Affiliated Stomatological Hospital of Southwest Medical University between January 2018 and June 2020, as well as 10 normal gingival tissue samples removed during the extraction of impacted teeth. OSCC cells HSC-4 were cultured routinely and divided into the control group (without virus), the NC group (transfected with control lentiviral vector), the shCCL1 group (transfected with knockdown CCL1 lentiviral vector), and the CCL1 group (culture medium containing 60 ng/mL CCL1 recombinant protein). Immunohistochemistry and WB were used to detect the expression of CCL1 in OSCC tissues and cells, and analyze the correlation between its expression level and the clinical features of patients. qPCR, CCK-8 assay, plate cloning assay, cell scratch test, Transwell assay and flow cytometry were used to detect the expression of CCL1 mRNA, the proliferation, migration and invasion abilities and the apoptosis of HSC-4 cells respectively. Results: CCL1 protein was highly expressed in OSCC tissues and HSC-4 cells (all P < 0.01) and its expression was related to the clinical stage of tumors (P < 0.05). The expression of CCL1 in HSC-4 cells was successfully knocked down (P < 0.000 5). Knocking down the expression of CCL1 could inhibit the proliferation (P < 0.05 or P < 0.01), migration and invasion (all P < 0.05) of HSC-4 cells, and promote its apoptosis (all P < 0.05). CCL1 recombinant protein treatment resulted in the opposite effects (P < 0.05, P < 0.01, P < 0.000 1). Conclusion: CCL1 is highly expressed in OSCC and its expression is correlated with the clinical stage of OSCC. CCL1 may take part in regulating the proliferation, migration, invasion and apoptosis of HSC-4 cells.
[Abstract] Objective: To explore the expression of chemokine ligand 1 (CCL1) in oral squamous cell carcinoma (OSCC) and its effect on the proliferation, migration and invasion of human oral tongue squamous cell carcinoma cells (HSC-4). Methods: 28 OSCC tissue samples and clinical characteristic data of patients were collected at the Affiliated Stomatological Hospital of Southwest Medical University between January 2018 and June 2020, as well as 10 normal gingival tissue samples removed during the extraction of impacted teeth. OSCC cells HSC-4 were cultured routinely and divided into the control group (without virus), the NC group (transfected with control lentiviral vector), the shCCL1 group (transfected with knockdown CCL1 lentiviral vector), and the CCL1 group (culture medium containing 60 ng/mL CCL1 recombinant protein). Immunohistochemistry and WB were used to detect the expression of CCL1 in OSCC tissues and cells, and analyze the correlation between its expression level and the clinical features of patients. qPCR, CCK-8 assay, plate cloning assay, cell scratch test, Transwell assay and flow cytometry were used to detect the expression of CCL1 mRNA, the proliferation, migration and invasion abilities and the apoptosis of HSC-4 cells respectively. Results: CCL1 protein was highly expressed in OSCC tissues and HSC-4 cells (all P < 0.01) and its expression was related to the clinical stage of tumors (P < 0.05). The expression of CCL1 in HSC-4 cells was successfully knocked down (P < 0.000 5). Knocking down the expression of CCL1 could inhibit the proliferation (P < 0.05 or P < 0.01), migration and invasion (all P < 0.05) of HSC-4 cells, and promote its apoptosis (all P < 0.05). CCL1 recombinant protein treatment resulted in the opposite effects (P < 0.05, P < 0.01, P < 0.000 1). Conclusion: CCL1 is highly expressed in OSCC and its expression is correlated with the clinical stage of OSCC. CCL1 may take part in regulating the proliferation, migration, invasion and apoptosis of HSC-4 cells.
ZHAO Wei
,
CUI Wenxuan
,
HUANG Beixuan
,
SHANG Xiaoya
,
WANG Zhenda
,
DU Yanyan
,
ZHAO Hongzheng
,
JIAO Wenjing
,
MA Ming
2025, 32(2):176-188.
DOI: 10.3872/j.issn.1007-385X.2025.02.006
Abstract:
[Abstract] Objective: To screen for microRNAs (miRNAs) highly expressed in the serum exosomes (Exo) of esophageal squamous cell carcinoma (ESCC) patients and analyze their relationship with the clinicopathological characteristics of the patients, and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC. Methods: Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected, serving as the control group and the ESCC group respectively. The Gene Expression Omnibus (GEO) database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246. The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve. The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression, and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test. Exosomes in the serum of the subjects were isolated, purified and characterized for verification. The expression of miR-1246 in Exo was detected by qPCR. ESCC KYSE150 and KYSE30 cells were routinely cultured. mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000. Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells, which were respectively denoted as the minics-NC, miR-1246 mimics, inhibitor-NC and miR-1246-inhibitor groups. KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups. The proliferation, migration and invasion abilities of cells in each group were detected by the CCK-8 assay, scratch wound healing assay and Transwell chamber assay respectively. The expressions of Exo markers, epithelial-mesenchymal transition-related proteins, TET family methylcytosine dioxygenase 2 (TET2) and cell adhesion molecule 1 (CADM1) proteins in each group of cells were detected by WB assay. The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay. Results: Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246. The serum Exo extracted from the patients conformed to the typical Exo characteristics. The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects (P < 0.01); the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ (P < 0.01). ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC (P < 0.05), and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag (P < 0.05). The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging (P < 0.01). Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients (P < 0.05). The expression level of serum Exo-miR-1246 was associated with the T-stage, N-stage and clinical stage of ESCC (P < 0.01). Overexpression of miR-1246 could promote the proliferation, migration, invasion, epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells, while inhibition of miR-1246 had the opposite effect. Database data analysis found that TET2 and CADM1 were the target genes of miR-1246. The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions (P < 0.01). Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells. Conclusion: Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC. It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.
[Abstract] Objective: To screen for microRNAs (miRNAs) highly expressed in the serum exosomes (Exo) of esophageal squamous cell carcinoma (ESCC) patients and analyze their relationship with the clinicopathological characteristics of the patients, and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC. Methods: Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected, serving as the control group and the ESCC group respectively. The Gene Expression Omnibus (GEO) database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246. The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve. The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression, and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test. Exosomes in the serum of the subjects were isolated, purified and characterized for verification. The expression of miR-1246 in Exo was detected by qPCR. ESCC KYSE150 and KYSE30 cells were routinely cultured. mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000. Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells, which were respectively denoted as the minics-NC, miR-1246 mimics, inhibitor-NC and miR-1246-inhibitor groups. KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups. The proliferation, migration and invasion abilities of cells in each group were detected by the CCK-8 assay, scratch wound healing assay and Transwell chamber assay respectively. The expressions of Exo markers, epithelial-mesenchymal transition-related proteins, TET family methylcytosine dioxygenase 2 (TET2) and cell adhesion molecule 1 (CADM1) proteins in each group of cells were detected by WB assay. The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay. Results: Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246. The serum Exo extracted from the patients conformed to the typical Exo characteristics. The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects (P < 0.01); the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ (P < 0.01). ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC (P < 0.05), and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag (P < 0.05). The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging (P < 0.01). Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients (P < 0.05). The expression level of serum Exo-miR-1246 was associated with the T-stage, N-stage and clinical stage of ESCC (P < 0.01). Overexpression of miR-1246 could promote the proliferation, migration, invasion, epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells, while inhibition of miR-1246 had the opposite effect. Database data analysis found that TET2 and CADM1 were the target genes of miR-1246. The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions (P < 0.01). Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells. Conclusion: Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC. It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.
2025, 32(2):189-198.
DOI: 10.3872/j.issn.1007-385X.2025.02.007
Abstract:
[Abstract] Objective: To explore the predictive value of combined evaluation of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) on the therapeutic effect and prognosis of ICIs (immune checkpoint inhibitors) in metastatic gastric cancer (MGC) patients. Methods: This study conducted a retrospective analysis of pre- and posttreatment peripheral hematological indicators of 88 MGC patients treated at Nanping First Hospital affiliated to Fujian Medical University. The recent treatment efficacy of the two patient groups was evaluated based on the solid tumor response evaluation criteria. χ2 tests were conducted to analyze and compare differences in disease control rate (DCR) and objective response rate (ORR), as well as differences in PD-L1 expression and clinical characteristics between the two groups. Survival analysis was performed using the Kaplan-Meier method for univariate analysis. Intergroup differences were detected by the Log-Rank test. Univariate analysis was conducted using the Cox proportional hazards regression model. Results: After immunotherapy, NLR3, NLR4, PLR2, PLR3, PLR4, LDH2 and LDH3 decreased significantly compared with those before treatment (all P < 0.05). There were significant statistical differences in NLR1 and LDH1 before treatment between the complete-remission (CR) + partial-remission (PR) group and the progressdisease (PD) group (all P < 0.05). Patients with higher levels of NLR2, NLR3, NLR4, PLR4, LDH1, LDH3, LDH4, ΔNLR1, ΔNLR2, ΔNLR3 and ΔPLR1 had shorter OS (all P < 0.05), and patients with higher levels of NLR2, NLR3, NLR4, PLR1, LDH1, ΔNLR1, ΔNLR2, ΔNLR3, ΔPLR1 and ΔPLR2 had shorter PFS compared with patients in low-level group (all P < 0.05). The percentage of PD-L1 negative patients among NLR3-H patients was the highest, and the number of NLR3-H patients in the NLR3-L group was larger than that in the negative group, the combined positive score (CPS) =1-5 group and the CPS ≥ 5 group (all P < 0.05). The proportion of women in the NLR3-H and PLR3-H groups was higher (all P < 0.05). Conclusion: The evaluation of NLR, PLR, and LDH has certain value in predicting the efficacy and prognosis of immunotherapy for MGC.
[Abstract] Objective: To explore the predictive value of combined evaluation of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) on the therapeutic effect and prognosis of ICIs (immune checkpoint inhibitors) in metastatic gastric cancer (MGC) patients. Methods: This study conducted a retrospective analysis of pre- and posttreatment peripheral hematological indicators of 88 MGC patients treated at Nanping First Hospital affiliated to Fujian Medical University. The recent treatment efficacy of the two patient groups was evaluated based on the solid tumor response evaluation criteria. χ2 tests were conducted to analyze and compare differences in disease control rate (DCR) and objective response rate (ORR), as well as differences in PD-L1 expression and clinical characteristics between the two groups. Survival analysis was performed using the Kaplan-Meier method for univariate analysis. Intergroup differences were detected by the Log-Rank test. Univariate analysis was conducted using the Cox proportional hazards regression model. Results: After immunotherapy, NLR3, NLR4, PLR2, PLR3, PLR4, LDH2 and LDH3 decreased significantly compared with those before treatment (all P < 0.05). There were significant statistical differences in NLR1 and LDH1 before treatment between the complete-remission (CR) + partial-remission (PR) group and the progressdisease (PD) group (all P < 0.05). Patients with higher levels of NLR2, NLR3, NLR4, PLR4, LDH1, LDH3, LDH4, ΔNLR1, ΔNLR2, ΔNLR3 and ΔPLR1 had shorter OS (all P < 0.05), and patients with higher levels of NLR2, NLR3, NLR4, PLR1, LDH1, ΔNLR1, ΔNLR2, ΔNLR3, ΔPLR1 and ΔPLR2 had shorter PFS compared with patients in low-level group (all P < 0.05). The percentage of PD-L1 negative patients among NLR3-H patients was the highest, and the number of NLR3-H patients in the NLR3-L group was larger than that in the negative group, the combined positive score (CPS) =1-5 group and the CPS ≥ 5 group (all P < 0.05). The proportion of women in the NLR3-H and PLR3-H groups was higher (all P < 0.05). Conclusion: The evaluation of NLR, PLR, and LDH has certain value in predicting the efficacy and prognosis of immunotherapy for MGC.
2025, 32(2):199-205.
DOI: 10.3872/j.issn.1007-385X.2025.02.008
Abstract:
[摘 要] 炎症反应，尤其是慢性炎症与肿瘤发生发展、转移等关系密切，是确切的驱动因素之一。IL-1β作为一种非常重要的 多效应促炎性细胞因子，在机体免疫炎症、病原体或非病原体感染免疫中具有广泛的免疫反应激活、免疫效应放大的调控功能。 在肿瘤免疫中，IL-1β由于其细胞来源、作用环境或调控方式的不同而产生促癌或抑癌的双向调控效应其在肿瘤生长、侵袭、转移 等方面表现出积极的促癌效应已引起国内外学者的极大关注，其多途径的促癌效应及调控机制也得到较为充分的研究和明确， 而基于促癌机制的相关靶点药物亦处于多线研发中，有的已进入临床试验期，并获得了较为理想的临床治疗效果。本文主要归 纳总结了IL-1β的多途径促癌效应及分子调控机制，并简要讨论了其抑癌功能及作用机制。
[摘 要] 炎症反应，尤其是慢性炎症与肿瘤发生发展、转移等关系密切，是确切的驱动因素之一。IL-1β作为一种非常重要的 多效应促炎性细胞因子，在机体免疫炎症、病原体或非病原体感染免疫中具有广泛的免疫反应激活、免疫效应放大的调控功能。 在肿瘤免疫中，IL-1β由于其细胞来源、作用环境或调控方式的不同而产生促癌或抑癌的双向调控效应其在肿瘤生长、侵袭、转移 等方面表现出积极的促癌效应已引起国内外学者的极大关注，其多途径的促癌效应及调控机制也得到较为充分的研究和明确， 而基于促癌机制的相关靶点药物亦处于多线研发中，有的已进入临床试验期，并获得了较为理想的临床治疗效果。本文主要归 纳总结了IL-1β的多途径促癌效应及分子调控机制，并简要讨论了其抑癌功能及作用机制。
2025, 32(2):206-212.
DOI: 10.3872/j.issn.1007-385X.2025.02.009
Abstract:
[摘 要] 鉴于固有免疫在肿瘤免疫监视中的重要作用，探索肿瘤环境下的固有免疫途径活化对于肿瘤治疗具有重要临床意义。 在肿瘤环境下，肿瘤细胞自身染色体不稳定或因肿瘤治疗导致的DNA损伤，以及线粒体功能障碍引起的线粒体dsDNA释放，均可 被胞质内环鸟苷酸-腺苷酸合酶（cGAS）捕获，从而激活干扰素基因刺激因子（STING）。STING作为固有免疫信号通路的一部分，自 身以及cGAS-STING通路在抗肿瘤中发挥重要作用；其中cGAS-STING通路主要介导干扰素和促炎性细胞因子产生，而STING自 身在肿瘤微环境中具有多重功能。考虑到STING在免疫细胞和非免疫细胞中普遍存在，本文重点总结了肿瘤微环境下STING在 肿瘤细胞与免疫细胞中涉及的抗肿瘤机制，包括影响肿瘤细胞自身活力、提高免疫细胞对肿瘤细胞识别能力与抗肿瘤活性、增强免 疫细胞间抗肿瘤协同作用等。此外，本文还概述了STING作为肿瘤治疗靶点在激动剂单药治疗和联合治疗的最新进展。
[摘 要] 鉴于固有免疫在肿瘤免疫监视中的重要作用，探索肿瘤环境下的固有免疫途径活化对于肿瘤治疗具有重要临床意义。 在肿瘤环境下，肿瘤细胞自身染色体不稳定或因肿瘤治疗导致的DNA损伤，以及线粒体功能障碍引起的线粒体dsDNA释放，均可 被胞质内环鸟苷酸-腺苷酸合酶（cGAS）捕获，从而激活干扰素基因刺激因子（STING）。STING作为固有免疫信号通路的一部分，自 身以及cGAS-STING通路在抗肿瘤中发挥重要作用；其中cGAS-STING通路主要介导干扰素和促炎性细胞因子产生，而STING自 身在肿瘤微环境中具有多重功能。考虑到STING在免疫细胞和非免疫细胞中普遍存在，本文重点总结了肿瘤微环境下STING在 肿瘤细胞与免疫细胞中涉及的抗肿瘤机制，包括影响肿瘤细胞自身活力、提高免疫细胞对肿瘤细胞识别能力与抗肿瘤活性、增强免 疫细胞间抗肿瘤协同作用等。此外，本文还概述了STING作为肿瘤治疗靶点在激动剂单药治疗和联合治疗的最新进展。
2025, 32(2):213-218.
DOI: 10.3872/j.issn.1007-385X.2025.02.010
Abstract:
[摘 要] 肿瘤相关脂肪微环境(TAAME）是一种由正常脂肪组织及肿瘤相关脂肪细胞、脂肪细胞源性成纤维细胞等新型细胞 共同组成的结构，通常存在于乳腺癌等富含脂肪组织的实体肿瘤中。在乳腺癌发展过程中，乳腺癌细胞有利于TAAME中各种新 型脂肪细胞的形成。同时，TAAME中的各种脂肪细胞通过分泌脂肪因子、脂肪酸等活性物质促进乳腺癌的增殖、转移及影响癌 细胞代谢等。二者间的“对话”机制使乳腺癌细胞不断适应外界变化，诱导肿瘤耐药等问题，致使乳腺癌治疗效果不佳。靶向 TAAME中的各种脂肪细胞、分泌因子等可有效抑制乳腺癌的进展。为此，本文对TAAME促进乳腺癌发展的分子机制进行分 析，进一步探讨了针对TAAME开展的靶向治疗、免疫治疗、中药治疗、纳米治疗等新辅助治疗策略，为临床治疗乳腺癌提供了新 思路。
[摘 要] 肿瘤相关脂肪微环境(TAAME）是一种由正常脂肪组织及肿瘤相关脂肪细胞、脂肪细胞源性成纤维细胞等新型细胞 共同组成的结构，通常存在于乳腺癌等富含脂肪组织的实体肿瘤中。在乳腺癌发展过程中，乳腺癌细胞有利于TAAME中各种新 型脂肪细胞的形成。同时，TAAME中的各种脂肪细胞通过分泌脂肪因子、脂肪酸等活性物质促进乳腺癌的增殖、转移及影响癌 细胞代谢等。二者间的“对话”机制使乳腺癌细胞不断适应外界变化，诱导肿瘤耐药等问题，致使乳腺癌治疗效果不佳。靶向 TAAME中的各种脂肪细胞、分泌因子等可有效抑制乳腺癌的进展。为此，本文对TAAME促进乳腺癌发展的分子机制进行分 析，进一步探讨了针对TAAME开展的靶向治疗、免疫治疗、中药治疗、纳米治疗等新辅助治疗策略，为临床治疗乳腺癌提供了新 思路。
2025, 32(2):219-225.
DOI: 10.3872/j.issn.1007-385X.2025.02.011
Abstract:
[摘 要] 氧化固醇是胆固醇的氧化合成衍生物，通过酶促或非酶促氧化过程产生，具有一系列的生物活性。作为胆固醇分解 代谢的中间体，氧化固醇广泛存在于人体的多种组织和体液中，生理浓度下其对正常代谢细胞过程中的胆固醇稳态、脂质代谢、 细胞凋亡、自噬等发挥多种调节作用。近年来，越来越多的研究表明氧化固醇在肿瘤、心血管疾病和自身免疫性疾病等病理过程 中起着关键性的作用。阐明氧化固醇在肿瘤发生发展过程中的分子调控机制并寻找肿瘤相关治疗靶点是备受关注的科学问题。 故本文主要从影响肿瘤细胞的死亡、增殖、生长和分化、肿瘤免疫细胞等方面总结和讨论了氧化固醇调节肿瘤发生发展的机制及 其作为肿瘤生物标志物和肿瘤治疗靶标的潜在临床应用价值，以对肿瘤发生发展过程中复杂的氧化甾醇系统有一个更清晰的理 解和认识。
[摘 要] 氧化固醇是胆固醇的氧化合成衍生物，通过酶促或非酶促氧化过程产生，具有一系列的生物活性。作为胆固醇分解 代谢的中间体，氧化固醇广泛存在于人体的多种组织和体液中，生理浓度下其对正常代谢细胞过程中的胆固醇稳态、脂质代谢、 细胞凋亡、自噬等发挥多种调节作用。近年来，越来越多的研究表明氧化固醇在肿瘤、心血管疾病和自身免疫性疾病等病理过程 中起着关键性的作用。阐明氧化固醇在肿瘤发生发展过程中的分子调控机制并寻找肿瘤相关治疗靶点是备受关注的科学问题。 故本文主要从影响肿瘤细胞的死亡、增殖、生长和分化、肿瘤免疫细胞等方面总结和讨论了氧化固醇调节肿瘤发生发展的机制及 其作为肿瘤生物标志物和肿瘤治疗靶标的潜在临床应用价值，以对肿瘤发生发展过程中复杂的氧化甾醇系统有一个更清晰的理 解和认识。
2025, 32(2):226-229.
DOI: 10.3872/j.issn.1007-385X.2025.02.012
Abstract:
[摘 要] 酪氨酸激酶抑制剂的出现显著改善了费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）患者的预后。然而，对于合并有 高危遗传学改变的患者效果差，如T315I突变的出现可导致疾病进展。本研究报告了3例合并高危遗传学改变的Ph+ ALL患者， 在使用第二代酪氨酸激酶抑制剂（TKI）和化疗后达到完全缓解，但 MRD 转阴困难，并快速复发。复发后，3 例患者均检测到 T315I突变。3例均联用奥雷巴替尼及化疗，1疗程均达到形态学缓解、MRD转阴、BCR-ABL融合基因同步转阴。因此，伴高危遗 传学改变的Ph+ ALL发生T315I突变时接受奥雷巴替尼治疗能快速达到分子生物学缓解；奥雷巴替尼是否可以一线使用值得进一 步探讨。
[摘 要] 酪氨酸激酶抑制剂的出现显著改善了费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）患者的预后。然而，对于合并有 高危遗传学改变的患者效果差，如T315I突变的出现可导致疾病进展。本研究报告了3例合并高危遗传学改变的Ph+ ALL患者， 在使用第二代酪氨酸激酶抑制剂（TKI）和化疗后达到完全缓解，但 MRD 转阴困难，并快速复发。复发后，3 例患者均检测到 T315I突变。3例均联用奥雷巴替尼及化疗，1疗程均达到形态学缓解、MRD转阴、BCR-ABL融合基因同步转阴。因此，伴高危遗 传学改变的Ph+ ALL发生T315I突变时接受奥雷巴替尼治疗能快速达到分子生物学缓解；奥雷巴替尼是否可以一线使用值得进一 步探讨。
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- 《中国肿瘤生物治疗杂志》
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- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
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- 刊号：ISSN 1007-385X
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.