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Volume 30,Issue 10,2023 Table of Contents
2023, 30(10):855-861.
DOI: 10.3872/j.issn.1007-385X.2023.10.001
Abstract:
CD8+ T cells are the major players in anti-tumor immune responses. Immune therapies have made significant breakthroughs in the field of cancer treatment by reshaping the ability of CD8+ T cells to kill tumor cells. But clinical benefits have been limited to some patients and certain cancer types. The key to improving cancer immunotherapy depends on how to overcome the CD8+ T cell dysfunctions. In recent years, quite a few researches have revealed the stemness regulation mechanisms of CD8+ T cells,discovered that stem-like CD8+ T cells possess self-renewal and proliferation abilities and stated the importance of this cell subgroup in maintaining sustained cancer immunotherapy responses. In this paper, we will review the molecular and functional characteristics of stem-cell like CD8+ T cells, and the intrinsic and extrinsic influencing factors of CD8+ T cell stemness, summarize the present stemness reprogramming strategies targeting CD8+ T cells, and further look into the ideas and methods of improving the therapeutic efficacy of cancer immunotherapy through targeting CD8+ T cells stemness programs.
CD8+ T cells are the major players in anti-tumor immune responses. Immune therapies have made significant breakthroughs in the field of cancer treatment by reshaping the ability of CD8+ T cells to kill tumor cells. But clinical benefits have been limited to some patients and certain cancer types. The key to improving cancer immunotherapy depends on how to overcome the CD8+ T cell dysfunctions. In recent years, quite a few researches have revealed the stemness regulation mechanisms of CD8+ T cells,discovered that stem-like CD8+ T cells possess self-renewal and proliferation abilities and stated the importance of this cell subgroup in maintaining sustained cancer immunotherapy responses. In this paper, we will review the molecular and functional characteristics of stem-cell like CD8+ T cells, and the intrinsic and extrinsic influencing factors of CD8+ T cell stemness, summarize the present stemness reprogramming strategies targeting CD8+ T cells, and further look into the ideas and methods of improving the therapeutic efficacy of cancer immunotherapy through targeting CD8+ T cells stemness programs.
2023, 30(10):862-867.
DOI: 10.3872/j.issn.1007-385X.2023.10.002
Abstract:
Objective：：To investigate the expression of phosphoglycerate mutase 1 (PGAM1) in colorectal cancer (CRC) tissues and its correlation with the prognosis and explore its effects on the proliferation, migration and invasion of CRC cells. Methods: Cancer tissue samples and clinical data of 30 patients who underwent surgery at Tianjin Medical University Cancer Institute and Hospital between March 2003 and November 2008 were collected. Immunohistochemical staining was used to detect the protein expression of PGAM1 in CRC tissues and analyze the relationship between PGAM1 expression and patients’ clinicopathological characteristics. Kaplan‐Meier survival analysis was employed to compare the overall survival (OS) and progress-free survival (PFS) of patients with high and low PGAM1 expression in order to analyze the relationship between PGAM1 expression and the prognosis. HCT-116 and SW480 cells were transfected respectively with si-PGAM1 and si-NC plasmids using RNA interference technology. Western blotting was used to detect PGAM1 protein expression levels in cells transfected with si-PGAM1 and si-NC. Afterwards, CCK-8 and Transwell assays were used to detect the influence of PGAM1 knockdown on the proliferation, migration, and invasion of CRC cells. Results: In 30 CRC tissue samples, PGAM1 positive staining was localized in the cytoplasm of CRC cells, and 33.3% (10 among 30 samples) showed high PGAM1 expression levels. Although the high expression of PGAM1 had no correlation with sex, age, histological type, tumor size,lymph node metastasis, distant metastasis and TNM stage of CRC patients (all P>0.05), the OS and PFS was significantly shorter in patients with PGAM1 high expression than those with low expression. After PGAM1 knockdown the proliferation, migration and invasion abilities of CRC cells were greatly inhibited (all P<0.05). Conclusion: PGAM1 was highly-expressed in CRC tissues. The high expression of PGAM1 was correlated with poor prognosis. Knocking down PGAM1 significantly inhibited the proliferation,migration and invasion abilities of CRC cells. All these findings suggest that PGAM1 might be a promising biomarker for predicting the prognosis of CRC patients.
Objective：：To investigate the expression of phosphoglycerate mutase 1 (PGAM1) in colorectal cancer (CRC) tissues and its correlation with the prognosis and explore its effects on the proliferation, migration and invasion of CRC cells. Methods: Cancer tissue samples and clinical data of 30 patients who underwent surgery at Tianjin Medical University Cancer Institute and Hospital between March 2003 and November 2008 were collected. Immunohistochemical staining was used to detect the protein expression of PGAM1 in CRC tissues and analyze the relationship between PGAM1 expression and patients’ clinicopathological characteristics. Kaplan‐Meier survival analysis was employed to compare the overall survival (OS) and progress-free survival (PFS) of patients with high and low PGAM1 expression in order to analyze the relationship between PGAM1 expression and the prognosis. HCT-116 and SW480 cells were transfected respectively with si-PGAM1 and si-NC plasmids using RNA interference technology. Western blotting was used to detect PGAM1 protein expression levels in cells transfected with si-PGAM1 and si-NC. Afterwards, CCK-8 and Transwell assays were used to detect the influence of PGAM1 knockdown on the proliferation, migration, and invasion of CRC cells. Results: In 30 CRC tissue samples, PGAM1 positive staining was localized in the cytoplasm of CRC cells, and 33.3% (10 among 30 samples) showed high PGAM1 expression levels. Although the high expression of PGAM1 had no correlation with sex, age, histological type, tumor size,lymph node metastasis, distant metastasis and TNM stage of CRC patients (all P>0.05), the OS and PFS was significantly shorter in patients with PGAM1 high expression than those with low expression. After PGAM1 knockdown the proliferation, migration and invasion abilities of CRC cells were greatly inhibited (all P<0.05). Conclusion: PGAM1 was highly-expressed in CRC tissues. The high expression of PGAM1 was correlated with poor prognosis. Knocking down PGAM1 significantly inhibited the proliferation,migration and invasion abilities of CRC cells. All these findings suggest that PGAM1 might be a promising biomarker for predicting the prognosis of CRC patients.
2023, 30(10):868-873.
DOI: 10.3872/j.issn.1007-385X.2023.10.003
Abstract:
Objective: To investigate the impact of specific activation of G protein-coupled estrogen receptors (GPER) on the migration of colorectal cancer (CRC) cells, and explore the potential underlying mechanism. Methods: CRC RKO and SW480 cells were cultured in vitro and treated with 0.5 or 1.0 μmol/L GPER-specific activator (G-1). CCK-8 method, scratch test, and Transwell test were used to detect the effects of G-1 on CRC cell proliferation and migration. The impact of G-1/G-1+ reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) treatment on the mRNA and protein expressions of E-cadherin (E-Cad) and fibronectin (FN) in RKO cells was measured using qPCR and WB. The level of ROS in RKO cells was detected by flow cytometry. Results: The migration ability of RKO and SW480 cells after the treatment with G-1 was significantly reduced (all P<0.05). Additionally, G-1 treatment significantly increased the mRNA and protein expressions of E-cad and decreased the mRNA and protein expressions of FN in the cells (all P<0.05). G-1 treatment also stimulated the production of ROS in RKO cells. However, the protein expression changes of E-cad and FN caused by G-1 were partially reversed under the action of NAC. Conclusion: Speicific activation of GPER inhibits the migration of CRC cells by suppressing epithelial-mesenchymal transition (EMT). This inhibitory effect is likely mediated through the upregulation of ROS levels in CRC cells.
Objective: To investigate the impact of specific activation of G protein-coupled estrogen receptors (GPER) on the migration of colorectal cancer (CRC) cells, and explore the potential underlying mechanism. Methods: CRC RKO and SW480 cells were cultured in vitro and treated with 0.5 or 1.0 μmol/L GPER-specific activator (G-1). CCK-8 method, scratch test, and Transwell test were used to detect the effects of G-1 on CRC cell proliferation and migration. The impact of G-1/G-1+ reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) treatment on the mRNA and protein expressions of E-cadherin (E-Cad) and fibronectin (FN) in RKO cells was measured using qPCR and WB. The level of ROS in RKO cells was detected by flow cytometry. Results: The migration ability of RKO and SW480 cells after the treatment with G-1 was significantly reduced (all P<0.05). Additionally, G-1 treatment significantly increased the mRNA and protein expressions of E-cad and decreased the mRNA and protein expressions of FN in the cells (all P<0.05). G-1 treatment also stimulated the production of ROS in RKO cells. However, the protein expression changes of E-cad and FN caused by G-1 were partially reversed under the action of NAC. Conclusion: Speicific activation of GPER inhibits the migration of CRC cells by suppressing epithelial-mesenchymal transition (EMT). This inhibitory effect is likely mediated through the upregulation of ROS levels in CRC cells.
2023, 30(10):874-880.
DOI: 10.3872/j.issn.1007-385X.2023.10.004
Abstract:
Objective: To investigate whether ginkgolide B (GKB) inhibits the proliferation, apoptosis, migration and invasion of gastric cancer HGC-27 cells by blocking the PI3K/Akt/mTOR signaling pathway. Methods: Gastric cancer HGC-27 cells were divided into control group, low-dose GKB (100 mg/L) group, high-dose GKB (200 mg/L) group, high-dose GKB (200 mg/L)+740Y-P (PI3K activator) group, and Ly294002 (PI3K inhibitor) group. MTT and Edu, FCM, Transwell tests were used to detect the proliferation, apoptosis, migration and invasion abilities of HGC-27 cells in each group. The expressions of PI3K mRNA, Akt mRNA, mTOR mRNA, and the protein expressions of Ki-67, caspase-3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in cells of each group were detected by qPCR and Western blotting. A nude mouse transplanted tumor model of gastric cancer HGC-27 cells was established. The effect of GKB on the growth of transplanted tumors was observed. Wesern blotting was used to detect the protein expressions of Ki-67, caspase-3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in transplanted tumor tissues. Results: The results of in vitro experiments indicated that, compared with the control group, the proliferative activity, cell proliferation rate, the numbers of cell migration and invasion, the expression levels of PI3K mRNA, Akt mRNA and mTOR mRNA, and the protein expression levels of Ki-67, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR of HGC-27 cells in low-dose GKB group, high-dose GKB group and Ly294002 group, reduced significantly (all P<0.05). The apoptosis rate and the expression of caspase-3 protein increased significantly (all P<0.05). 740Y-P could partially reverse the inhibitory effect of GKB on HGC-27 cells (all P<0.05). Tumor-bearing nude mouse experience showed that GKB could significantly inhibit the growth of nude mouse transplanted tumors of HGC-27 cells (P<0.05) and downregulate the expressions of PI3K/Akt/mTOR pathway-related proteins. Conclusion: GKB may inhibit the proliferation, migration and invasion and promote the apoptosis of gastric cancer HGC-27 cells by blocking the PI3K/Akt/mTOR signaling pathway.
Objective: To investigate whether ginkgolide B (GKB) inhibits the proliferation, apoptosis, migration and invasion of gastric cancer HGC-27 cells by blocking the PI3K/Akt/mTOR signaling pathway. Methods: Gastric cancer HGC-27 cells were divided into control group, low-dose GKB (100 mg/L) group, high-dose GKB (200 mg/L) group, high-dose GKB (200 mg/L)+740Y-P (PI3K activator) group, and Ly294002 (PI3K inhibitor) group. MTT and Edu, FCM, Transwell tests were used to detect the proliferation, apoptosis, migration and invasion abilities of HGC-27 cells in each group. The expressions of PI3K mRNA, Akt mRNA, mTOR mRNA, and the protein expressions of Ki-67, caspase-3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in cells of each group were detected by qPCR and Western blotting. A nude mouse transplanted tumor model of gastric cancer HGC-27 cells was established. The effect of GKB on the growth of transplanted tumors was observed. Wesern blotting was used to detect the protein expressions of Ki-67, caspase-3, p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR in transplanted tumor tissues. Results: The results of in vitro experiments indicated that, compared with the control group, the proliferative activity, cell proliferation rate, the numbers of cell migration and invasion, the expression levels of PI3K mRNA, Akt mRNA and mTOR mRNA, and the protein expression levels of Ki-67, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR of HGC-27 cells in low-dose GKB group, high-dose GKB group and Ly294002 group, reduced significantly (all P<0.05). The apoptosis rate and the expression of caspase-3 protein increased significantly (all P<0.05). 740Y-P could partially reverse the inhibitory effect of GKB on HGC-27 cells (all P<0.05). Tumor-bearing nude mouse experience showed that GKB could significantly inhibit the growth of nude mouse transplanted tumors of HGC-27 cells (P<0.05) and downregulate the expressions of PI3K/Akt/mTOR pathway-related proteins. Conclusion: GKB may inhibit the proliferation, migration and invasion and promote the apoptosis of gastric cancer HGC-27 cells by blocking the PI3K/Akt/mTOR signaling pathway.
2023, 30(10):881-886.
DOI: 10.3872/j.issn.1007-385X.2023.10.005
Abstract:
Objective: To investigate the effects and the mechanisms of catalpol (Cat) , a herbal extract from rehmannia glutinosa, on the proliferation and apoptosis of MCF-7 cells and the growth of transplanted tumors in nude mice. Methods: Human breast cancer MCF-7 cells were treated in vitro with Cat of different mass concentrations (0, 5, 25, 50, 100, 200 μg/mL), and the concentration of Cat was screened by MTT method. MCF-7 cells were divided into blank control group, Cat low-dose group, Cat medium-dose group, Cat high-dose group, Cat+sh-NC group and Cat+sh-FOXO3 group. Edu cell proliferation assay, plate cloning assay and flow cytometry were used to detect cell proliferation and clonogenetic abilities, the apoptosis rate and the cell cycle in each group, respectively. The protein expressions of FOXO3, FOXM1, caspase-3 and caspase-8 in cells of each group were detected by WB. A nude mouse transplant model of breast cancer MCF-7 cells was constructed to observe the effects of Cat on the growth of transplanted tumors. The protein expressions of FOXO3 and FOXM1 in transplanted tumor tissues were detected by WB. Results: The proliferation ablities of MCF-7 cells treated with low (50 μg/mL), medium (100 μg/mL) and high (200 μg/mL) Cat doses decreased significantly (all P<0.05). Compared with blank control group, the Edu positive cell rate, the number of clones formed, S phase and G2/M phase cell ratio and FOXO3 protein expression in Cat low, medium and high dose groups decreased significantly (all P<0.05). The apoptosis rate, G0/G1 phase cell ratio and the protein expressions of FOXM1, caspase-3 and caspase-8 increased significantly (all P<0.05). Compared with those of Cat+sh-NC group, the Edu positive cell rate, the colony formation number, S phase to G2/M phase cell ratio and FOXO3 protein expression of Cat+sh-FOXO3 group increased significantly (all P<0.05). The apoptosis rate, G0/G1 phase cell ratio and the protein expressions of FOXM1, caspase-3 and caspase-8 decreased significantly (all P<0.05). In Cat group, the volume and weight of nude mouse transplant MCF-7 cell tumors and the protein expression of FOXO3 decreased significantly (all P<0.05), while the protein expression of FOXM1 increased significantly (P<0.05). Conclusion: Cat inhibits the proliferation and promotes the apoptosis of breast cancer MCF-7 cells and inhibits the growth of transplanted tumors in nude mice. The mechanisms may be related to the upregulation of FOXO3 expression and the downregulation of FOXM1 expression.
Objective: To investigate the effects and the mechanisms of catalpol (Cat) , a herbal extract from rehmannia glutinosa, on the proliferation and apoptosis of MCF-7 cells and the growth of transplanted tumors in nude mice. Methods: Human breast cancer MCF-7 cells were treated in vitro with Cat of different mass concentrations (0, 5, 25, 50, 100, 200 μg/mL), and the concentration of Cat was screened by MTT method. MCF-7 cells were divided into blank control group, Cat low-dose group, Cat medium-dose group, Cat high-dose group, Cat+sh-NC group and Cat+sh-FOXO3 group. Edu cell proliferation assay, plate cloning assay and flow cytometry were used to detect cell proliferation and clonogenetic abilities, the apoptosis rate and the cell cycle in each group, respectively. The protein expressions of FOXO3, FOXM1, caspase-3 and caspase-8 in cells of each group were detected by WB. A nude mouse transplant model of breast cancer MCF-7 cells was constructed to observe the effects of Cat on the growth of transplanted tumors. The protein expressions of FOXO3 and FOXM1 in transplanted tumor tissues were detected by WB. Results: The proliferation ablities of MCF-7 cells treated with low (50 μg/mL), medium (100 μg/mL) and high (200 μg/mL) Cat doses decreased significantly (all P<0.05). Compared with blank control group, the Edu positive cell rate, the number of clones formed, S phase and G2/M phase cell ratio and FOXO3 protein expression in Cat low, medium and high dose groups decreased significantly (all P<0.05). The apoptosis rate, G0/G1 phase cell ratio and the protein expressions of FOXM1, caspase-3 and caspase-8 increased significantly (all P<0.05). Compared with those of Cat+sh-NC group, the Edu positive cell rate, the colony formation number, S phase to G2/M phase cell ratio and FOXO3 protein expression of Cat+sh-FOXO3 group increased significantly (all P<0.05). The apoptosis rate, G0/G1 phase cell ratio and the protein expressions of FOXM1, caspase-3 and caspase-8 decreased significantly (all P<0.05). In Cat group, the volume and weight of nude mouse transplant MCF-7 cell tumors and the protein expression of FOXO3 decreased significantly (all P<0.05), while the protein expression of FOXM1 increased significantly (P<0.05). Conclusion: Cat inhibits the proliferation and promotes the apoptosis of breast cancer MCF-7 cells and inhibits the growth of transplanted tumors in nude mice. The mechanisms may be related to the upregulation of FOXO3 expression and the downregulation of FOXM1 expression.
2023, 30(10):887-892.
DOI: 10.3872/j.issn.1007-385X.2023.10.006
Abstract:
Objective: To investigate whether evodiamine (Evo) regulates the proliferation, migration and invasion of neuroblastoma SK-N-SH cells by regulating the expression of lncRNA LINC00858. Methods: Human neuroblastoma SK-N-SH cells were treated with 3, 6 and 12 μmol/L Evo in vitro. si-NC and si-LINC00858 were transfected into SK-N-SH cells by RNA interference technique; pcDNA and pcDNA-LINC00858 were transfected into SK-N-SH cells and treated with 12 μmol/L Evo. The cells were divided into control group, low dose Evo group, medium dose Evo group, high dose Evo group, si-NC group, si-LINC00858 group, Evo+pcDNA group and Evo+pcDNA-LINC00858 group. qPCR was used to detect the expression level of LINC00858 in the cells of each group. Cell proliferation, migration and invasion abilities were detected by MTT and Transwell assay. The expressions of cyclinD1, MMP-2, MMP-9 and p21 proteins were detected by WB assay. Results: Compared with the control group, the expressions of LINC00858 in SK-N-SH cells in Evo low, medium and high dose groups decreased (all P<0.05). The inhibitory rate of cell proliferation increased significantly, and the number of migration and invasion decreased significantly (all P<0.01). The protein expressions of cyclinD1, MMP-2 and MMP-9 decreased, while the protein expression of p21 increased (all P<0.01). Compared with si-NC group, the cell proliferation inhibition rate, the numbers of migration and invasion and the expressions of related proteins in si-LINC00858 group were the same as those in low-dose, medium-dose and high-dose Evo groups. Compared with Evo+pcDNA group, the proliferation inhibition rate of Evo+pcDNA-LINC00858 group decreased significantly, and the numbers of migration and invasion cells increased significantly (all P<0.01).The protein expressions of cyclinD1, MMP-2 and MMP-9 increased, and the protein expression of p21 decreased (all P<0.05). Conclusion: Evo inhibits the proliferation, migration and invasion of neuroblastoma SK-N-SH cells by down-regulating the expression of LINC00858.
Objective: To investigate whether evodiamine (Evo) regulates the proliferation, migration and invasion of neuroblastoma SK-N-SH cells by regulating the expression of lncRNA LINC00858. Methods: Human neuroblastoma SK-N-SH cells were treated with 3, 6 and 12 μmol/L Evo in vitro. si-NC and si-LINC00858 were transfected into SK-N-SH cells by RNA interference technique; pcDNA and pcDNA-LINC00858 were transfected into SK-N-SH cells and treated with 12 μmol/L Evo. The cells were divided into control group, low dose Evo group, medium dose Evo group, high dose Evo group, si-NC group, si-LINC00858 group, Evo+pcDNA group and Evo+pcDNA-LINC00858 group. qPCR was used to detect the expression level of LINC00858 in the cells of each group. Cell proliferation, migration and invasion abilities were detected by MTT and Transwell assay. The expressions of cyclinD1, MMP-2, MMP-9 and p21 proteins were detected by WB assay. Results: Compared with the control group, the expressions of LINC00858 in SK-N-SH cells in Evo low, medium and high dose groups decreased (all P<0.05). The inhibitory rate of cell proliferation increased significantly, and the number of migration and invasion decreased significantly (all P<0.01). The protein expressions of cyclinD1, MMP-2 and MMP-9 decreased, while the protein expression of p21 increased (all P<0.01). Compared with si-NC group, the cell proliferation inhibition rate, the numbers of migration and invasion and the expressions of related proteins in si-LINC00858 group were the same as those in low-dose, medium-dose and high-dose Evo groups. Compared with Evo+pcDNA group, the proliferation inhibition rate of Evo+pcDNA-LINC00858 group decreased significantly, and the numbers of migration and invasion cells increased significantly (all P<0.01).The protein expressions of cyclinD1, MMP-2 and MMP-9 increased, and the protein expression of p21 decreased (all P<0.05). Conclusion: Evo inhibits the proliferation, migration and invasion of neuroblastoma SK-N-SH cells by down-regulating the expression of LINC00858.
WANG Wanping
,
REN Mingjun
,
BI Wanying
,
LONG Yongwen
,
WANG Weiji
,
MENG Yijun
,
TANG Shifu
,
MENG Qiuxing
,
DENG Yaoming
2023, 30(10):893-901.
DOI: 10.3872/j.issn.1007-385X.2023.10.007
Abstract:
Objective: To investigate the expression level of hsa_circ_0078607 in colorectal cancer tissues and patients’ serum, and its correlation with clinicopathological characteristics of colorectal cancer patients, and to evaluate whether it can be used as a potential molecular diagnostic marker and therapeutic target for colorectal cancer. Methods: 58 pairs of colorectal cancer tissue and para-cancerous tissue specimens were collected from patients undergoing colorectal cancer resection surgery in the Department of Gastrointestinal Surgery of Liuzhou People's Hospital between June 2018 and January 2022. The serum of 152 colorectal cancer patients and colorectal polyp patients first diagnosed in Liuzhou People's Hospital between January 2020 and December 2022 and physical examination personnel was collected. The specifically highly expressed hsa_circ_0078607 was selected from the differentially expressed circRNAs profile of colorectal cancer as a candidate marker, qPCR was used to detect its relative expression levels in colorectal cancer cell lines, tissues and serum and the serum of colorectal polyp patients, and analyze its correlation with clinicopathological characteristics. The diagnostic value of hsa_circ_0078607 for colorectal cancer and colorectal polyp was evaluated by ROC curve. The miRNA binding to hsa_circ_0078607 was predicted by Circular RNA Interactome database, and the circRNA-miRNA-mRNA regulatory network was constructed by Cytoscape 3.9.1 software. At the same time, GO/KEGG enrichment analysis was used to further understand its function. Results: Compared with paracancerous tissue or serum from healthy people, hsa_circ_ 0078607 was highly expressed in colorectal cancer cells, tissues and serum and the serum of colorectal polyp patients (P<0.001). Its expression was up-regulated in the cancer tissues of 52 patients (89.7%), and was down-regulated in 6 patients (10.3%). The relative expression of hsa_circ_0078607 in colorectal cancer tissues was correlated with tumor location (P=0.029), degree of differentiation (P=0.046) and distant metastasis (P=0.043). The ROC results showed that the AUC of hsa_circ_0078607 for the diagnosis of colorectal cancer in tissue and serum was 0.845 7 (95%CI [0.772 8, 0.918 6], P<0.000 1) and 0.8683 (95%CI [0.790 7, 0.945 9], P<0.000 1), respectively; and in the serum of colorectal polyp patients, the AUC of hsa_circ_0078607 for the diagnosis of colorectal polyps was 0.710 1 (95%CI [0.610 0, 0.810 1]). GO/KEGG enrichment analysis results indicated that hsa_circ_0078607 downstream miRNAs may be involved in various biological processes, such as RNA polymerase Ⅱ promoter transcription regulation, protein K48-linked ubiquitination, Wnt, Hippo, and MAPK signaling pathway regulation. Conclusion: Hsa_circ_0078607 is highly expressed in colorectal cancer cells, tissues and serum, and its expression level in colorectal cancer tissues is correlated with tumor location, degree of differentiation and distant metastasis, suggesting that it can be used as a potential molecular diagnostic marker for colorectal cancer. At the same time, it may also mediate the occurrence and development of colorectal cancer, which is of great significance for discovering potential therapeutic targets of colorectal cancer.
Objective: To investigate the expression level of hsa_circ_0078607 in colorectal cancer tissues and patients’ serum, and its correlation with clinicopathological characteristics of colorectal cancer patients, and to evaluate whether it can be used as a potential molecular diagnostic marker and therapeutic target for colorectal cancer. Methods: 58 pairs of colorectal cancer tissue and para-cancerous tissue specimens were collected from patients undergoing colorectal cancer resection surgery in the Department of Gastrointestinal Surgery of Liuzhou People's Hospital between June 2018 and January 2022. The serum of 152 colorectal cancer patients and colorectal polyp patients first diagnosed in Liuzhou People's Hospital between January 2020 and December 2022 and physical examination personnel was collected. The specifically highly expressed hsa_circ_0078607 was selected from the differentially expressed circRNAs profile of colorectal cancer as a candidate marker, qPCR was used to detect its relative expression levels in colorectal cancer cell lines, tissues and serum and the serum of colorectal polyp patients, and analyze its correlation with clinicopathological characteristics. The diagnostic value of hsa_circ_0078607 for colorectal cancer and colorectal polyp was evaluated by ROC curve. The miRNA binding to hsa_circ_0078607 was predicted by Circular RNA Interactome database, and the circRNA-miRNA-mRNA regulatory network was constructed by Cytoscape 3.9.1 software. At the same time, GO/KEGG enrichment analysis was used to further understand its function. Results: Compared with paracancerous tissue or serum from healthy people, hsa_circ_ 0078607 was highly expressed in colorectal cancer cells, tissues and serum and the serum of colorectal polyp patients (P<0.001). Its expression was up-regulated in the cancer tissues of 52 patients (89.7%), and was down-regulated in 6 patients (10.3%). The relative expression of hsa_circ_0078607 in colorectal cancer tissues was correlated with tumor location (P=0.029), degree of differentiation (P=0.046) and distant metastasis (P=0.043). The ROC results showed that the AUC of hsa_circ_0078607 for the diagnosis of colorectal cancer in tissue and serum was 0.845 7 (95%CI [0.772 8, 0.918 6], P<0.000 1) and 0.8683 (95%CI [0.790 7, 0.945 9], P<0.000 1), respectively; and in the serum of colorectal polyp patients, the AUC of hsa_circ_0078607 for the diagnosis of colorectal polyps was 0.710 1 (95%CI [0.610 0, 0.810 1]). GO/KEGG enrichment analysis results indicated that hsa_circ_0078607 downstream miRNAs may be involved in various biological processes, such as RNA polymerase Ⅱ promoter transcription regulation, protein K48-linked ubiquitination, Wnt, Hippo, and MAPK signaling pathway regulation. Conclusion: Hsa_circ_0078607 is highly expressed in colorectal cancer cells, tissues and serum, and its expression level in colorectal cancer tissues is correlated with tumor location, degree of differentiation and distant metastasis, suggesting that it can be used as a potential molecular diagnostic marker for colorectal cancer. At the same time, it may also mediate the occurrence and development of colorectal cancer, which is of great significance for discovering potential therapeutic targets of colorectal cancer.
2023, 30(10):902-907.
DOI: 10.3872/j.issn.1007-385X.2023.10.008
Abstract:
Objective: To construct the inflammatory response score (IRS) system according to the expression levels of neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in patients with gastric cancerbefore operation, and to analyze the influence of IRS on postoperative prognosis of patients with gastric cancer and construct a nomogram prediction model. Methods: The clinical data of 211 gastric cancer patients admitted to the Department of General Surgery of Yichun People's Hospital between January 2016 and January 2020 were collected, 198 among whom were successfully followed up. According to their survival status 3 years after surgery, these 198 patients were divided into the death group (n=93) and the survival group (n=105). The general clinical data of the two groups were compared. The independent risk factors affecting the prognosis of patients with gastric cancer were analyzed by multivariate COX regression risk model, and the nomogram prediction model was constructed by the R Package rms. Results: There were significant differences in maximum tumor diameter, pathological stage, T stage,differentiation degree, nerve invasion, vascular invasion, NLR, PLR and LMR between the 2 groups (all P<0.05). According to the construction criteria of NLP, PLR and LMR-IRS (NPL-IRS), the OS rate of gastric cancer patients with different scores showed a certain grade trend difference (χ2=61.129, P<0.01). Pathological stage Ⅲ, low differentiation, vascular invasion, NPL-IRS>1 score were independent risk factors for the prognosis of gastric cancer patients (P<0.05). Decision curve analysis showed that this predictive model could provide significant additional clinical net benefit at a risk threshold of >0.16. Conclusion: The nomogram prediction model based on pathological stage Ⅲ, low differentiation, vascular invasion, and NPL-IRS>1 score can provide important strategic guidance for the prognosis assessment of gastric cancer patients.
Objective: To construct the inflammatory response score (IRS) system according to the expression levels of neutrophil to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in patients with gastric cancerbefore operation, and to analyze the influence of IRS on postoperative prognosis of patients with gastric cancer and construct a nomogram prediction model. Methods: The clinical data of 211 gastric cancer patients admitted to the Department of General Surgery of Yichun People's Hospital between January 2016 and January 2020 were collected, 198 among whom were successfully followed up. According to their survival status 3 years after surgery, these 198 patients were divided into the death group (n=93) and the survival group (n=105). The general clinical data of the two groups were compared. The independent risk factors affecting the prognosis of patients with gastric cancer were analyzed by multivariate COX regression risk model, and the nomogram prediction model was constructed by the R Package rms. Results: There were significant differences in maximum tumor diameter, pathological stage, T stage,differentiation degree, nerve invasion, vascular invasion, NLR, PLR and LMR between the 2 groups (all P<0.05). According to the construction criteria of NLP, PLR and LMR-IRS (NPL-IRS), the OS rate of gastric cancer patients with different scores showed a certain grade trend difference (χ2=61.129, P<0.01). Pathological stage Ⅲ, low differentiation, vascular invasion, NPL-IRS>1 score were independent risk factors for the prognosis of gastric cancer patients (P<0.05). Decision curve analysis showed that this predictive model could provide significant additional clinical net benefit at a risk threshold of >0.16. Conclusion: The nomogram prediction model based on pathological stage Ⅲ, low differentiation, vascular invasion, and NPL-IRS>1 score can provide important strategic guidance for the prognosis assessment of gastric cancer patients.
2023, 30(10):908-913.
DOI: 10.3872/j.issn.1007-385X.2023.10.009
Abstract:
Objective: To provide a new basis for the differential diagnosis of immune-related adverse events (irAEs) and infectious inflammation by comparing the changes of the main indicators in blood routine examination before and after the occurrence of irAEs.Methods: The clinical data of 201 patients with malignant tumors who had irAEs after receiving anti-PD-1 antibody therapy in Henan Cancer Hospital between August 2018 and June 2022 were retrospectively analyzed. The main indicators of blood routine examination before anti-PD-1 antibody treatment, before and after irAEs were collected. The statistical differences of blood routine index values before and after treatment were analyzed by paired t-test. Chi-square test was used to analyze the statistical difference in the positive rate (the proportion of blood routine index values above normal) before and after treatment. Results: 258 irAEs were observed in the 201 patients, of which 27 (13.4%) developed 2 or more types of irAEs, and 214 (82.94%) irAEs did not cause fever; The white blood cell count (t=1.087, P=0.278), neutrophil count (t=0.959, P=0.338) and neutrophil percentage (t=0.817, P=0.414) did not increase significantly after irAEs compared with those before anti-PD-1 antibody treatment. The numbers of cases above the normal value were 28 vs 38 (χ2=1.737, P=0.187), 32 vs 44 (χ2=2.222, P=0.136), 45 vs 55 (χ2=1.240, P=0.265), and the differences were not statistically significant. Conclusion: After the occurrence of irAEs, there were no significant changes in peripheral blood white blood cell count, neutrophil count and neutrophil percentage, which may be of reference significance for the differential diagnosis of infectious inflammation.
Objective: To provide a new basis for the differential diagnosis of immune-related adverse events (irAEs) and infectious inflammation by comparing the changes of the main indicators in blood routine examination before and after the occurrence of irAEs.Methods: The clinical data of 201 patients with malignant tumors who had irAEs after receiving anti-PD-1 antibody therapy in Henan Cancer Hospital between August 2018 and June 2022 were retrospectively analyzed. The main indicators of blood routine examination before anti-PD-1 antibody treatment, before and after irAEs were collected. The statistical differences of blood routine index values before and after treatment were analyzed by paired t-test. Chi-square test was used to analyze the statistical difference in the positive rate (the proportion of blood routine index values above normal) before and after treatment. Results: 258 irAEs were observed in the 201 patients, of which 27 (13.4%) developed 2 or more types of irAEs, and 214 (82.94%) irAEs did not cause fever; The white blood cell count (t=1.087, P=0.278), neutrophil count (t=0.959, P=0.338) and neutrophil percentage (t=0.817, P=0.414) did not increase significantly after irAEs compared with those before anti-PD-1 antibody treatment. The numbers of cases above the normal value were 28 vs 38 (χ2=1.737, P=0.187), 32 vs 44 (χ2=2.222, P=0.136), 45 vs 55 (χ2=1.240, P=0.265), and the differences were not statistically significant. Conclusion: After the occurrence of irAEs, there were no significant changes in peripheral blood white blood cell count, neutrophil count and neutrophil percentage, which may be of reference significance for the differential diagnosis of infectious inflammation.
2023, 30(10):914-918.
DOI: 10.3872/j.issn.1007-385X.2023.10.010
Abstract:
胞葬作用是吞噬细胞清除凋亡细胞的过程，具有抗炎和促瘤作用。胞葬作用作为在肿瘤微环境（TME）中发生频率最高的事件之一，能对肿瘤细胞的增殖、凋亡、转移和侵袭，以及抗肿瘤免疫等生物学特征产生重要影响。胞葬作用过程中的复杂代谢状态可以通过“找我（find me）”、“吃我（eat me）”信号和释放降解产物影响肿瘤的发生与发展。此外，胞葬作用可促进肿瘤相关巨噬细胞（TAM）极化为M2表型、调节抗炎因子和促炎细胞因子分泌以及调节T细胞、NK细胞等免疫细胞的激活和成熟，产生一系列的抗炎和免疫抑制信号，影响TME，从而促进肿瘤细胞逃避免疫监视机制，导致肿瘤进展。从胞葬作用角度出发探讨肿瘤治疗的潜在靶点，为抗肿瘤药物的研发提供新的思路。
胞葬作用是吞噬细胞清除凋亡细胞的过程，具有抗炎和促瘤作用。胞葬作用作为在肿瘤微环境（TME）中发生频率最高的事件之一，能对肿瘤细胞的增殖、凋亡、转移和侵袭，以及抗肿瘤免疫等生物学特征产生重要影响。胞葬作用过程中的复杂代谢状态可以通过“找我（find me）”、“吃我（eat me）”信号和释放降解产物影响肿瘤的发生与发展。此外，胞葬作用可促进肿瘤相关巨噬细胞（TAM）极化为M2表型、调节抗炎因子和促炎细胞因子分泌以及调节T细胞、NK细胞等免疫细胞的激活和成熟，产生一系列的抗炎和免疫抑制信号，影响TME，从而促进肿瘤细胞逃避免疫监视机制，导致肿瘤进展。从胞葬作用角度出发探讨肿瘤治疗的潜在靶点，为抗肿瘤药物的研发提供新的思路。
2023, 30(10):919-924.
DOI: 10.3872/j.issn.1007-385X.2023.10.011
Abstract:
铁死亡是一种新型的铁依赖的程序性细胞死亡，常伴随脂质过氧化物的异常累积。Hippo 通路是一种高度进化保守的蛋白激酶信号通路，通过调节下游效应蛋白YAP/TAZ的亚细胞定位和蛋白稳定性，参与调节细胞的多种生命活动，包括组织生长、干细胞分化、肿瘤的发生发展等。近年来的研究发现，Hippo-YAP/TAZ信号通路通过细胞密度、细胞接触、细胞代谢、机械信号等多种细胞外途径影响肿瘤细胞对铁死亡的敏感性，在不同类型的肿瘤组织中通过特定的刺激条件、铁死亡靶向蛋白及其分子机制，影响泌尿、生殖、消化、呼吸和内分泌系统等肿瘤的发生和发展。Hippo-YAP/TAZ信号通路作为铁死亡新的调节机制，其激活为转移性及耐药性肿瘤的治疗提供了新的思路和方向。
铁死亡是一种新型的铁依赖的程序性细胞死亡，常伴随脂质过氧化物的异常累积。Hippo 通路是一种高度进化保守的蛋白激酶信号通路，通过调节下游效应蛋白YAP/TAZ的亚细胞定位和蛋白稳定性，参与调节细胞的多种生命活动，包括组织生长、干细胞分化、肿瘤的发生发展等。近年来的研究发现，Hippo-YAP/TAZ信号通路通过细胞密度、细胞接触、细胞代谢、机械信号等多种细胞外途径影响肿瘤细胞对铁死亡的敏感性，在不同类型的肿瘤组织中通过特定的刺激条件、铁死亡靶向蛋白及其分子机制，影响泌尿、生殖、消化、呼吸和内分泌系统等肿瘤的发生和发展。Hippo-YAP/TAZ信号通路作为铁死亡新的调节机制，其激活为转移性及耐药性肿瘤的治疗提供了新的思路和方向。
2023, 30(10):925-930.
DOI: 10.3872/j.issn.1007-385X.2023.10.012
Abstract:
寻找对肿瘤免疫原性具有关键调控作用的生物治疗靶点是抑制肿瘤免疫逃逸、提高肿瘤免疫治疗效果的关键。锌指蛋白（ZFP）通过与DNA、RNA、蛋白质的相互作用，调控肿瘤抗原的形成、肿瘤表面MHC分子及其共刺激分子的表达、损伤相关分子模式的释放等，影响肿瘤细胞的免疫原性及肿瘤微环境（TME）中免疫细胞的分布和功能，进而在调节抗肿瘤免疫应答和肿瘤免疫逃逸中发挥重要作用。近年来，临床前及临床研究探索将ZFP 相关的生物治疗方法应用于肿瘤免疫治疗，主要聚焦在免疫检查点阻断治疗、免疫细胞治疗，以及免疫治疗联合治疗策略展现出了可喜的应用前景。
寻找对肿瘤免疫原性具有关键调控作用的生物治疗靶点是抑制肿瘤免疫逃逸、提高肿瘤免疫治疗效果的关键。锌指蛋白（ZFP）通过与DNA、RNA、蛋白质的相互作用，调控肿瘤抗原的形成、肿瘤表面MHC分子及其共刺激分子的表达、损伤相关分子模式的释放等，影响肿瘤细胞的免疫原性及肿瘤微环境（TME）中免疫细胞的分布和功能，进而在调节抗肿瘤免疫应答和肿瘤免疫逃逸中发挥重要作用。近年来，临床前及临床研究探索将ZFP 相关的生物治疗方法应用于肿瘤免疫治疗，主要聚焦在免疫检查点阻断治疗、免疫细胞治疗，以及免疫治疗联合治疗策略展现出了可喜的应用前景。
2023, 30(10):931-936.
DOI: 10.3872/j.issn.1007-385X.2023.10.013
Abstract:
鼠类肉瘤病毒癌基因（KRAS）是非小细胞肺癌（NSCLC）中最常见的致癌基因之一，由于KRAS蛋白表面相对平滑，缺少可结合小分子的药物口袋，长期以来被视为“不可用药的靶点”。最近针对KRASG12C基因点突变的靶向药物相继在临床研究中取得了一定进展，特别是KRASG12C特异性抑制剂阿达格拉西布（adagrasib）和索托拉西布（sotorasib）的应用给NSCLC患者治疗带来了希望。携带KRAS基因突变的肿瘤具有巨大的肿瘤异质性，且KRASG12C抑制剂存在明显的耐药问题，其机制可能与KRAS基因的二次突变或扩增、旁路激活和组织学转化等有关。KRAS基因参与多种调节细胞生存和增殖的信号通路，了解其耐药机制对开发可能的治疗策略应对耐药至关重要。KRASG12C共价抑制剂与免疫抑制剂及各靶向药物联用现已相继进入临床试验，将有效增强和推动KRASG12C共价抑制剂在NSCLC治疗中的应用。
鼠类肉瘤病毒癌基因（KRAS）是非小细胞肺癌（NSCLC）中最常见的致癌基因之一，由于KRAS蛋白表面相对平滑，缺少可结合小分子的药物口袋，长期以来被视为“不可用药的靶点”。最近针对KRASG12C基因点突变的靶向药物相继在临床研究中取得了一定进展，特别是KRASG12C特异性抑制剂阿达格拉西布（adagrasib）和索托拉西布（sotorasib）的应用给NSCLC患者治疗带来了希望。携带KRAS基因突变的肿瘤具有巨大的肿瘤异质性，且KRASG12C抑制剂存在明显的耐药问题，其机制可能与KRAS基因的二次突变或扩增、旁路激活和组织学转化等有关。KRAS基因参与多种调节细胞生存和增殖的信号通路，了解其耐药机制对开发可能的治疗策略应对耐药至关重要。KRASG12C共价抑制剂与免疫抑制剂及各靶向药物联用现已相继进入临床试验，将有效增强和推动KRASG12C共价抑制剂在NSCLC治疗中的应用。
2023, 30(10):937-939.
DOI: 10.3872/j.issn.1007-385X.2023.10.014
Abstract:
结膜恶性黑色素瘤是一种罕见的眼部恶性肿瘤，患者预后差，常见转移器官有肺、脑、肝、骨等，尚无胃转移的报道。本文报道1例结膜恶性黑色素瘤胃转移的病例（男性，76岁），结膜恶性黑色素瘤术后1.5年，因“乏力、纳差、心悸”就诊，胃镜病理诊断为恶性黑色素瘤。治疗方案：PD-1抑制剂联合化疗；具体用药：替雷利珠单抗200 mg d0+替莫唑胺胶囊240 mg d1~d5 q3w。治疗后评估患者症状明显改善，血红蛋白恢复正常，腹部CT示：胃底部软组织肿块明显缩小，疗效显著，至目前病情稳定，控制时间达17个月以上。本例诊治经验或能为结膜恶性黑色素瘤胃转移这一罕见病例提供一种新的治疗选择。
结膜恶性黑色素瘤是一种罕见的眼部恶性肿瘤，患者预后差，常见转移器官有肺、脑、肝、骨等，尚无胃转移的报道。本文报道1例结膜恶性黑色素瘤胃转移的病例（男性，76岁），结膜恶性黑色素瘤术后1.5年，因“乏力、纳差、心悸”就诊，胃镜病理诊断为恶性黑色素瘤。治疗方案：PD-1抑制剂联合化疗；具体用药：替雷利珠单抗200 mg d0+替莫唑胺胶囊240 mg d1~d5 q3w。治疗后评估患者症状明显改善，血红蛋白恢复正常，腹部CT示：胃底部软组织肿块明显缩小，疗效显著，至目前病情稳定，控制时间达17个月以上。本例诊治经验或能为结膜恶性黑色素瘤胃转移这一罕见病例提供一种新的治疗选择。
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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.