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Volume 31,Issue 9,2024 Table of Contents
2024, 31(9):841-848.
DOI: 10.3872/j.issn.1007-385X.2024.09.001
Abstract:
Tumor immunotherapy is an emerging and promising therapeutic modality. Mesothelin, a cell surface membrane protein anchored by glycosylated phosphatidylinositol, is highly expressed in a variety of malignant solid tumors and hematological malignancies, but lowly expressed in the mesothelial cells of a few normal tissues, making it a promising target for tumor immunotherapy. High mesothelin expression is closely associated with poor prognosis patients, and soluble mesothelin has become a diagnostic biomarker for a variety of tumors. Immunotherapeutic strategies, such as antibody-drug conjugates and CAR-T cell therapy, are undergoing translational research for mesothelin-positive solid tumors, achieving preliminary progress. This paper systematically describes the structure, in vivo distribution, biological functions, and intracellular signaling mechanisms of mesothelin in tumor cells. It also covers targeted imaging and therapeutic strategies based on nuclides, antibody-drug conjugates and CAR-T cells, along with the associated challenges. These insights provide a new perspective for further exploration of mesothelin-targeted immunotherapies.
Tumor immunotherapy is an emerging and promising therapeutic modality. Mesothelin, a cell surface membrane protein anchored by glycosylated phosphatidylinositol, is highly expressed in a variety of malignant solid tumors and hematological malignancies, but lowly expressed in the mesothelial cells of a few normal tissues, making it a promising target for tumor immunotherapy. High mesothelin expression is closely associated with poor prognosis patients, and soluble mesothelin has become a diagnostic biomarker for a variety of tumors. Immunotherapeutic strategies, such as antibody-drug conjugates and CAR-T cell therapy, are undergoing translational research for mesothelin-positive solid tumors, achieving preliminary progress. This paper systematically describes the structure, in vivo distribution, biological functions, and intracellular signaling mechanisms of mesothelin in tumor cells. It also covers targeted imaging and therapeutic strategies based on nuclides, antibody-drug conjugates and CAR-T cells, along with the associated challenges. These insights provide a new perspective for further exploration of mesothelin-targeted immunotherapies.
WANG Shun
,
YU Jiaqi
,
HU Yue
,
ZHAO Zhenglin
,
NIU Shudong
,
JIA Di
,
YANG Chao
,
YI Tonghui
,
LI Shuyan
2024, 31(9):849-856.
DOI: 10.3872/j.issn.1007-385X.2024.09.002
Abstract:
Objective: To analyze the effects of arginine-glycine-aspartic acid (RGD) modification on anti-hepatocarcinoma activity of tumstatin peptide 19 (T-19) and to comparatively analyze the effects of tumor suppressor peptide 19 (T-19) and RGD modified-T-19 (RGD-T-19) on the proliferation, invasion, migration of on liver cancer SK-Hep-1 cells. Methods: T-19 and RGD-T-19 were synthesized by Fmoc solid-phase method and separated and identified using high-performance liquid chromatography and mass spectrometry. SK-Hep-1 cells were routinely cultured and treated with 0, 50, 100, 150, 200, and 250 mg/mL of T-19 and RGD-T-19, respectively. The cells were divided into control group (0 mg/mL), 50 mg/mL group, 100 mg/mL group, 150 mg/mL group, 200 mg/mL group, and 250 mg/mL group. CCK-8 assay and clone formation test were used to detect the effects of T-19 and RGD-T-19 on the viability and proliferation of SK-hep-1 cells. The invasion and migration of SK-Hep-1 cells were observed by scratch and Transwell test. The mRNA expression of cellular matrix metalloproteinases MMP-2 and MMP-9 was detected by qPCR. The protein expression of COX-2, MMP-2, MMP-9, TIMP-1, and TIMP-2 was detected by Western blot. Results: The synthesized T-19 and RGD-T-19 were identified to be of high purity by mass spectroscopy. Both T-19 and RGD-T-19 significantly inhibited the proliferation, migration, and invasion abilities of SK-Hep-1 cells, suppressed the protein expression of COX-2 and both the mRNA and protein expression of MMP-2, and MMP-9, but promoted the protein expression of TIMP-1 and TIMP-2 (P < 0.05, P < 0.01, P < 0.001). Notably, the inhibitory or promoting effects of RGD-T-19 were significantly stronger than those of T-19 (P < 0.05). Conclusion: T-19 and RGD-T-19 synthesized by Fmoc solid-phase method were highly pure and eligible. Both T-19 and RGD-T-19 can inhibit the proliferation, invasion, and migration of SK-Hep-1 cells, with better effects of RGD-T-19 than T-19.
Objective: To analyze the effects of arginine-glycine-aspartic acid (RGD) modification on anti-hepatocarcinoma activity of tumstatin peptide 19 (T-19) and to comparatively analyze the effects of tumor suppressor peptide 19 (T-19) and RGD modified-T-19 (RGD-T-19) on the proliferation, invasion, migration of on liver cancer SK-Hep-1 cells. Methods: T-19 and RGD-T-19 were synthesized by Fmoc solid-phase method and separated and identified using high-performance liquid chromatography and mass spectrometry. SK-Hep-1 cells were routinely cultured and treated with 0, 50, 100, 150, 200, and 250 mg/mL of T-19 and RGD-T-19, respectively. The cells were divided into control group (0 mg/mL), 50 mg/mL group, 100 mg/mL group, 150 mg/mL group, 200 mg/mL group, and 250 mg/mL group. CCK-8 assay and clone formation test were used to detect the effects of T-19 and RGD-T-19 on the viability and proliferation of SK-hep-1 cells. The invasion and migration of SK-Hep-1 cells were observed by scratch and Transwell test. The mRNA expression of cellular matrix metalloproteinases MMP-2 and MMP-9 was detected by qPCR. The protein expression of COX-2, MMP-2, MMP-9, TIMP-1, and TIMP-2 was detected by Western blot. Results: The synthesized T-19 and RGD-T-19 were identified to be of high purity by mass spectroscopy. Both T-19 and RGD-T-19 significantly inhibited the proliferation, migration, and invasion abilities of SK-Hep-1 cells, suppressed the protein expression of COX-2 and both the mRNA and protein expression of MMP-2, and MMP-9, but promoted the protein expression of TIMP-1 and TIMP-2 (P < 0.05, P < 0.01, P < 0.001). Notably, the inhibitory or promoting effects of RGD-T-19 were significantly stronger than those of T-19 (P < 0.05). Conclusion: T-19 and RGD-T-19 synthesized by Fmoc solid-phase method were highly pure and eligible. Both T-19 and RGD-T-19 can inhibit the proliferation, invasion, and migration of SK-Hep-1 cells, with better effects of RGD-T-19 than T-19.
2024, 31(9):857-863.
DOI: 10.3872/j.issn.1007-385X.2024.09.003
Abstract:
Objective: To investigate the effects of mesenchymal to epithelial transition factors (MET) knockdown on the proliferation, migration, and sensitivity to 5-FU and cisplatin in human laryngeal squamous cell carcinoma (LSCC) Hep-2 cells. Methods: The expression of MET mRNA in LSCC tissues was analyzed using data from the Gene Expression Omnibus (GEO) and The Cancer and Tumor Gene Atlas (TCGA). Human normal bronchial epithelial cells (16HBE) and human LSCC cells (Hep-2, KBV200 and TU212) were routinely cultured, and the expression levels of MET in these cells were detected by qPCR and WB assay. The MET knockout plasmid (si-Met) and control plasmid (si-NC) were transfected into Hep-2 cells using LipofectamineTM 3000, and the cells were divided into blank control group, si-NC group and si-Met group. The proliferation, migration, cell cycle distribution, and sensitivity to 5-FU and cisplatin of Hep-2 cells in each group were detected by MTT assay, flow cytometry and scratch assay, respectively. Results: Database analysis showed high expression of MET mRNA in LSCC tissue (P < 0.05). The mRNA and protein expression levels of MET in Hep2 cells, KBV200 cells and TU212 cells were significantly higher than those in 16HBE cells (all P < 0.01). After MET knockdown, the mRNA and protein levels of MET in Hep-2 cells were significantly reduced (P < 0.01 or P < 0.001), cell proliferation activity was significantly decreased (P < 0.000 1), the number of G0/G1 phase cells was significantly increased (P < 0.000 1), and the number of S phase cells was significantly reduced. Additionally, after MET knockdown, the inhibitory rates of cell proliferation by different concentrations of 5-FU or cisplatin were significantly enhanced, and the half maximal inhibitory concentration (IC50) was reduced (all P < 0.000 1). The scratch healing rate and migration ability were significantly reduced (all P < 0.05). Conclusion: MET is highly expressed in human LSCC tissues and cells. Knocking down MET can effectively inhibit the expression of MET in Hep-2 cells, suppress cell proliferation and migration ability, arrest the cell cycle in G1 phase, and enhance the sensitivity of Hep-2 cells to 5-FU and cisplatin.
Objective: To investigate the effects of mesenchymal to epithelial transition factors (MET) knockdown on the proliferation, migration, and sensitivity to 5-FU and cisplatin in human laryngeal squamous cell carcinoma (LSCC) Hep-2 cells. Methods: The expression of MET mRNA in LSCC tissues was analyzed using data from the Gene Expression Omnibus (GEO) and The Cancer and Tumor Gene Atlas (TCGA). Human normal bronchial epithelial cells (16HBE) and human LSCC cells (Hep-2, KBV200 and TU212) were routinely cultured, and the expression levels of MET in these cells were detected by qPCR and WB assay. The MET knockout plasmid (si-Met) and control plasmid (si-NC) were transfected into Hep-2 cells using LipofectamineTM 3000, and the cells were divided into blank control group, si-NC group and si-Met group. The proliferation, migration, cell cycle distribution, and sensitivity to 5-FU and cisplatin of Hep-2 cells in each group were detected by MTT assay, flow cytometry and scratch assay, respectively. Results: Database analysis showed high expression of MET mRNA in LSCC tissue (P < 0.05). The mRNA and protein expression levels of MET in Hep2 cells, KBV200 cells and TU212 cells were significantly higher than those in 16HBE cells (all P < 0.01). After MET knockdown, the mRNA and protein levels of MET in Hep-2 cells were significantly reduced (P < 0.01 or P < 0.001), cell proliferation activity was significantly decreased (P < 0.000 1), the number of G0/G1 phase cells was significantly increased (P < 0.000 1), and the number of S phase cells was significantly reduced. Additionally, after MET knockdown, the inhibitory rates of cell proliferation by different concentrations of 5-FU or cisplatin were significantly enhanced, and the half maximal inhibitory concentration (IC50) was reduced (all P < 0.000 1). The scratch healing rate and migration ability were significantly reduced (all P < 0.05). Conclusion: MET is highly expressed in human LSCC tissues and cells. Knocking down MET can effectively inhibit the expression of MET in Hep-2 cells, suppress cell proliferation and migration ability, arrest the cell cycle in G1 phase, and enhance the sensitivity of Hep-2 cells to 5-FU and cisplatin.
2024, 31(9):864-870.
DOI: 10.3872/j.issn.1007-385X.2024.09.004
Abstract:
Objective: To investigate the effects of serine/arginine-rich splicing factor 7 (SRSF7) on proliferation, migration and invasion of hepatocellular carcinoma (HCC) HepG2 cells and the possible mechanisms. Methods: Differential expression of SRSF7 between HCC and adjacent non-tumor tissues and its relationship with patient prognosis were analyzed online using The Cancer Genome Atlas (TCGA) and Kaplan Meier Plotter. HepG2 cells were cultured routinely and transfected with SRSF7 RNA knockdown sequences (siSRSF7#1 and siSRSF7#2), control sequences (NC), SRSF7 overexpression vector (hSRSF7-oe), and control vector (hSRSF7-nc) using transfection reagents. Accordingly, the cells were divided into NC group, siSRSF7#1 group, siSRSF7#2 group, NC + hSRSF7-nc group, siSRSF7 + hSRSF7-nc group, and siSRSF7 + hSRSF7-oe group. The mRNA and protein expression levels of SRSF7 in each group of cells were detected by qPCR and WB assay. The proliferation, migration, and invasion abilities of each group of cells were assessed by MTS assay, plate clone formation assay, scratch assay, and Transwell invasion assay. WB assay was used to detect the expression of JAK1/STAT3 signaling pathway related proteins in HepG2 cells of each group. Results: Database analysis showed that SRSF7 mRNA is highly expressed in HCC tissues (P < 0.001), and its high expression is associated with poor prognosis in HCC patients (P < 0.05). Knockdown of SRSF7 significantly reduced the proliferation, migration, and invasion abilities of HepG2 cells (all P < 0.01). The phosphorylation levels of JAK1 and STAT3 in the SRSF7 knockdown cells were significantly reduced (both P < 0.05), while overexpression of SRSF7 resulted in a significant increase in JAK1 and STAT3 phosphorylation levels (both P < 0.05). Conclusion: SRSF7 is highly expressed in HCC tissues and may promote the proliferation, migration, and invasion of HepG2 cells by regulating the JAK1/STAT3 signaling pathway.
Objective: To investigate the effects of serine/arginine-rich splicing factor 7 (SRSF7) on proliferation, migration and invasion of hepatocellular carcinoma (HCC) HepG2 cells and the possible mechanisms. Methods: Differential expression of SRSF7 between HCC and adjacent non-tumor tissues and its relationship with patient prognosis were analyzed online using The Cancer Genome Atlas (TCGA) and Kaplan Meier Plotter. HepG2 cells were cultured routinely and transfected with SRSF7 RNA knockdown sequences (siSRSF7#1 and siSRSF7#2), control sequences (NC), SRSF7 overexpression vector (hSRSF7-oe), and control vector (hSRSF7-nc) using transfection reagents. Accordingly, the cells were divided into NC group, siSRSF7#1 group, siSRSF7#2 group, NC + hSRSF7-nc group, siSRSF7 + hSRSF7-nc group, and siSRSF7 + hSRSF7-oe group. The mRNA and protein expression levels of SRSF7 in each group of cells were detected by qPCR and WB assay. The proliferation, migration, and invasion abilities of each group of cells were assessed by MTS assay, plate clone formation assay, scratch assay, and Transwell invasion assay. WB assay was used to detect the expression of JAK1/STAT3 signaling pathway related proteins in HepG2 cells of each group. Results: Database analysis showed that SRSF7 mRNA is highly expressed in HCC tissues (P < 0.001), and its high expression is associated with poor prognosis in HCC patients (P < 0.05). Knockdown of SRSF7 significantly reduced the proliferation, migration, and invasion abilities of HepG2 cells (all P < 0.01). The phosphorylation levels of JAK1 and STAT3 in the SRSF7 knockdown cells were significantly reduced (both P < 0.05), while overexpression of SRSF7 resulted in a significant increase in JAK1 and STAT3 phosphorylation levels (both P < 0.05). Conclusion: SRSF7 is highly expressed in HCC tissues and may promote the proliferation, migration, and invasion of HepG2 cells by regulating the JAK1/STAT3 signaling pathway.
2024, 31(9):871-877.
DOI: 10.3872/j.issn.1007-385X.2024.09.005
Abstract:
Objective: To explore how germacrone regulates the proliferation, migration and chemoresistance of human thyroid cancer BCPAP cells and doxorubicin (DOX) resistant BCPAP cells (BCPAP/DOX) through the forkhead box O3 (FOXO3)-FOX subclass M1 transcription factor (FOXM1) signaling pathway. Methods: BCPAP cells were cultured routinely and used to construct BCPAP/DOX cells. MTT method was applied to detect the effects of different concentrations of germacrone on the proliferation of BCPAP and BCPAP/DOX cells. BCPAP and BCPAP/DOX cells were divided into control group (Ctrl), negative control group (NC, transfected with sh-NC plasmid), low concentration germacrone group (0.10 mmol/L), high concentration germacrone group (0.15 mmol/L), high concentration germacrone (0.15 mmol/L) + sh-FOXO3 group (transfected with sh-FOXO3 plasmid). The sh-NC plasmid and sh-FOXO3 plasmid were transfected into the corresponding BCPAP and BCPAP/DOX cells with transfection reagents. The proliferation and migration of the cells were detected using CCK-8 assay and scratching healing assay, and the expression of FOXO3, FOXM1, BAX, MMP-9 and multi-drug resistant-1 (MDR-1) was detected using WB assay. Results: The expression of FOXO3 was successfully knocked down in BCPAP and BCPAP/DOX cells. Both low and high concentrations of germacrone could significantly inhibit the proliferation and migration of BCPAP and BCPAP/DOX cells, reduce the protein expression of FOMX1, MMP-9 or MDR-1 (in BCPAP/ DOX cells), and increase the protein expression of FOXO3 and BAX (all P < 0.05). Notably, the effects were more significant with high concentration germacrone compared to that of low concentration (all P < 0.05). Knockdown of FOXO3 partially reversed the effects of germacrone on these cells (all P < 0.05). Conclusion: Germacrone may regulate the proliferation and migration of BCPAP and BCPAP/DOX cells and reduce chemotherapy resistance of BCPAP/DOX cells through the FOXO3/FOXM1 signaling pathway.
Objective: To explore how germacrone regulates the proliferation, migration and chemoresistance of human thyroid cancer BCPAP cells and doxorubicin (DOX) resistant BCPAP cells (BCPAP/DOX) through the forkhead box O3 (FOXO3)-FOX subclass M1 transcription factor (FOXM1) signaling pathway. Methods: BCPAP cells were cultured routinely and used to construct BCPAP/DOX cells. MTT method was applied to detect the effects of different concentrations of germacrone on the proliferation of BCPAP and BCPAP/DOX cells. BCPAP and BCPAP/DOX cells were divided into control group (Ctrl), negative control group (NC, transfected with sh-NC plasmid), low concentration germacrone group (0.10 mmol/L), high concentration germacrone group (0.15 mmol/L), high concentration germacrone (0.15 mmol/L) + sh-FOXO3 group (transfected with sh-FOXO3 plasmid). The sh-NC plasmid and sh-FOXO3 plasmid were transfected into the corresponding BCPAP and BCPAP/DOX cells with transfection reagents. The proliferation and migration of the cells were detected using CCK-8 assay and scratching healing assay, and the expression of FOXO3, FOXM1, BAX, MMP-9 and multi-drug resistant-1 (MDR-1) was detected using WB assay. Results: The expression of FOXO3 was successfully knocked down in BCPAP and BCPAP/DOX cells. Both low and high concentrations of germacrone could significantly inhibit the proliferation and migration of BCPAP and BCPAP/DOX cells, reduce the protein expression of FOMX1, MMP-9 or MDR-1 (in BCPAP/ DOX cells), and increase the protein expression of FOXO3 and BAX (all P < 0.05). Notably, the effects were more significant with high concentration germacrone compared to that of low concentration (all P < 0.05). Knockdown of FOXO3 partially reversed the effects of germacrone on these cells (all P < 0.05). Conclusion: Germacrone may regulate the proliferation and migration of BCPAP and BCPAP/DOX cells and reduce chemotherapy resistance of BCPAP/DOX cells through the FOXO3/FOXM1 signaling pathway.
2024, 31(9):878-887.
DOI: 10.3872/j.issn.1007-385X.2024.09.006
Abstract:
Objective: To investigate the expression of group 2 innate lymphoid cells (ILC2s) and myeloid-derived suppressor cells (MDSCs), along with their associated cytokines IL-13 and inducible nitric oxide synthase (iNOS), in cervical cancer (CC), and to construct a nomogram prediction model for assessing the risk of CC based on these factors. Methods: Samples were collected from May 2022 to January 2024 at the First Affiliated Hospital of Xinjiang Medical University, including 40 cases of CC tissue and 100 cases of peripheral blood as the CC group. Concurrently, cervical tissues from 30 cases of uterine fibroids screened negative for CC and peripheral blood from 100 healthy individuals were selected as the control group. Multiple immunofluorescence technology (mIF) and immunohistochemical staining (IHC) were utilized to detect the infiltration of ILC2s and MDSCs in tissue samples from both groups, along with the expression levels of related cytokines IL-13 and iNOS. Flow cytometry (FCM) and ELISA were employed to assess the differences in ILC2s, MDSCs, IL-13, and iNOS expression in peripheral blood samples. Pearson correlation was used to assess their correlations. Univariate and multivariate logistic analyses were performed to determine whether ILC2s, MDSCs, IL-13, and iNOS are independent risk factors for CC. An immune prediction model was established using R software, and the model was evaluated using the area under the ROC curve (AUC value), Hosmer-Lemeshow test, calibration curve, clinical decision curve, and clinical impact curve.Results: The levels of ILC2, MDSC, IL-13 and iNOS were all significantly higher in the CC group compared to the control group (all P < 0.05). Furthermore, they were positively correlated (all P < 0.05). Univariate and multivariate logistic regression analyses indicated that ILC2, MDSC, IL-13, and iNOS are independent risk factors for the development of CC (all P < 0.05). Subsequently, a nomogram based on these risk factors was developed and verified to have practical clinical value. Conclusion: ILC2, MDSC, and their associated cytokines IL-13 and iNOS are highly expressed in CC tissues and peripheral blood. The prediction model incorporating these risk factors has predictive capabilities and clinical utility, providing a valuable and accessible tool for early diagnosis and treatment of cervical cancer.
Objective: To investigate the expression of group 2 innate lymphoid cells (ILC2s) and myeloid-derived suppressor cells (MDSCs), along with their associated cytokines IL-13 and inducible nitric oxide synthase (iNOS), in cervical cancer (CC), and to construct a nomogram prediction model for assessing the risk of CC based on these factors. Methods: Samples were collected from May 2022 to January 2024 at the First Affiliated Hospital of Xinjiang Medical University, including 40 cases of CC tissue and 100 cases of peripheral blood as the CC group. Concurrently, cervical tissues from 30 cases of uterine fibroids screened negative for CC and peripheral blood from 100 healthy individuals were selected as the control group. Multiple immunofluorescence technology (mIF) and immunohistochemical staining (IHC) were utilized to detect the infiltration of ILC2s and MDSCs in tissue samples from both groups, along with the expression levels of related cytokines IL-13 and iNOS. Flow cytometry (FCM) and ELISA were employed to assess the differences in ILC2s, MDSCs, IL-13, and iNOS expression in peripheral blood samples. Pearson correlation was used to assess their correlations. Univariate and multivariate logistic analyses were performed to determine whether ILC2s, MDSCs, IL-13, and iNOS are independent risk factors for CC. An immune prediction model was established using R software, and the model was evaluated using the area under the ROC curve (AUC value), Hosmer-Lemeshow test, calibration curve, clinical decision curve, and clinical impact curve.Results: The levels of ILC2, MDSC, IL-13 and iNOS were all significantly higher in the CC group compared to the control group (all P < 0.05). Furthermore, they were positively correlated (all P < 0.05). Univariate and multivariate logistic regression analyses indicated that ILC2, MDSC, IL-13, and iNOS are independent risk factors for the development of CC (all P < 0.05). Subsequently, a nomogram based on these risk factors was developed and verified to have practical clinical value. Conclusion: ILC2, MDSC, and their associated cytokines IL-13 and iNOS are highly expressed in CC tissues and peripheral blood. The prediction model incorporating these risk factors has predictive capabilities and clinical utility, providing a valuable and accessible tool for early diagnosis and treatment of cervical cancer.
2024, 31(9):888-894.
DOI: 10.3872/j.issn.1007-385X.2024.09.007
Abstract:
Objective: To investigate the expression of structural maintenance of chromosome 4 (SMC4) in breast cancer and its prognostic value. Methods: The expression of SMC4 gene in breast cancer tissues and its correlation with the clinicopathological characteristics of patients were analyzed using the TIMER, GEPIA, UALCAN and GEO databases. The expression of SMC4 protein in breast cancer and adjacent normal tissues was detected using immunohistochemical (IHC) staining. Correlations between SMC4 expression and clinicopathological features of breast cancer were evaluated. The relationship between SMC4 expression and survival of patients with breast cancer was evaluated by Kaplan-Meier, GEPIA database, Cox proportional hazards regression model. Results: Bioinformatics analysis showed that the mRNA level of SMC4 in breast cancer tissues was significantly higher than that in normal adjacent tissues (P < 0.01), and was closely related to clinical stage, lymph node metastasis and chemotherapy resistance (all P < 0.05). IHC staining showed that the positive and strong positive rates of SMC4 in breast cancer tissues were significantly higher than those in normal adjacent tissues (all P < 0.05). The high protein expression of SMC4 was closely related to the age, clinical stage and lymph node metastasis of breast cancer patients (all P < 0.05). The cumulative survival rate of patients in SMC4 low expression group was significantly higher than that in the SMC4 high expression group, especially in patients with HER2+ breast cancer (P < 0.05). Additionally, SMC4 is an independent risk factor for prognosis in patients with breast cancer. Conclusion: SMC4 is highly expressed in breast cancer tissues. High SMC4 expression is closely related to lymph node metastasis, clinical stage, and prognosis of patients with breast cancer, making it a potential marker for the diagnosis and prognosis of breast cancer.
Objective: To investigate the expression of structural maintenance of chromosome 4 (SMC4) in breast cancer and its prognostic value. Methods: The expression of SMC4 gene in breast cancer tissues and its correlation with the clinicopathological characteristics of patients were analyzed using the TIMER, GEPIA, UALCAN and GEO databases. The expression of SMC4 protein in breast cancer and adjacent normal tissues was detected using immunohistochemical (IHC) staining. Correlations between SMC4 expression and clinicopathological features of breast cancer were evaluated. The relationship between SMC4 expression and survival of patients with breast cancer was evaluated by Kaplan-Meier, GEPIA database, Cox proportional hazards regression model. Results: Bioinformatics analysis showed that the mRNA level of SMC4 in breast cancer tissues was significantly higher than that in normal adjacent tissues (P < 0.01), and was closely related to clinical stage, lymph node metastasis and chemotherapy resistance (all P < 0.05). IHC staining showed that the positive and strong positive rates of SMC4 in breast cancer tissues were significantly higher than those in normal adjacent tissues (all P < 0.05). The high protein expression of SMC4 was closely related to the age, clinical stage and lymph node metastasis of breast cancer patients (all P < 0.05). The cumulative survival rate of patients in SMC4 low expression group was significantly higher than that in the SMC4 high expression group, especially in patients with HER2+ breast cancer (P < 0.05). Additionally, SMC4 is an independent risk factor for prognosis in patients with breast cancer. Conclusion: SMC4 is highly expressed in breast cancer tissues. High SMC4 expression is closely related to lymph node metastasis, clinical stage, and prognosis of patients with breast cancer, making it a potential marker for the diagnosis and prognosis of breast cancer.
2024, 31(9):895-906.
DOI: 10.3872/j.issn.1007-385X.2024.09.008
Abstract:
Objective: To investigate the expression of eight subunits of chaperonin containing t-complex 1 (CCT) in thyroid cancer (TC) tissues and their correlation with TC staging, patient prognosis, immune cell infiltration, immune checkpoint expression, and chemotherapy drug sensitivity. Methods: Data from The Cancer Genome Atlas (TCGA) database were used to analyze the expression of each CCT subunit in TC tissues and para-cancerous tissues as well as their relationship with the prognosis of TC patients. The biological function of each CCT subunit was analyzed by the Gene Set Enrichment Analysis (GSEA). Data from the TCGA and TIMER2.0 databases were used to analyze the correlations between the expression of each CCT subunit and the tumor microenvironment, infiltration of immune cells, chemotherapeutic drug sensitivity, and immune checkpoint expression. Results: Database analysis showed high mRNA expression of CCT3, CCT7, and CCT8 and low mRNA expression of CCT1, CCT2, CCT5, and CCT6B in TC tissues (P < 0.01 or P < 0.001). CCT3, CCT6B, and CCT8 mRNA expression were correlated with T staging (P < 0.05 or P < 0.01); CCT6B mRNA expression was associated with lymph node metastasis (P < 0.01); CCT5 mRNA expression was associated with distant metastasis (P < 0.05); and CCT6B may serve as an independent prognostic biomarker for overall survival (OS) in TC patients. CCT subunit expression was primarily enriched in signaling pathways such as graft rejection, complement, and interferongamma.Low expression groups of CCT subunits demonstrated significantly higher TC stromal score, immune infiltration score and composite score than the high expression groups (P < 0.05 or P < 0.01 or P < 0.001), displaying a negative correlation between the expression of each CCT subunit and TC stromal, immune infiltration and composite scores (all P < 0.01). The mRNA expression of each CCT subunit was positively correlated with CD8+ T cell and macrophage infiltration (all P < 0.05), the mRNA expression of most CCT subunits (except CCT6B and CCT7) was positively correlated with neutrophil infiltration (P < 0.05 or P < 0.01 or P < 0.001), whereas the mRNA expression of CCT3, 4, 7, and 8 was negatively correlated with CD4+ T-cell infiltration (all P < 0.05). Compared to the low-expression group, patients with high mRNA expression of most CCT subunit had significantly higher IC50 for chemotherapeutic agents such as sorafenib, levatinib, darafenib, trametinib, vandetanib, and cabozantinib (all P < 0.05 or P < 0.01 or P < 0.001). CCT subunit expression in TC tissues was significantly correlated with the expression of PD-1, PD-L1, PD-L2, CTLA4, CD80, and CD86 (P < 0.05 or P < 0.01 or P < 0.001). Conclusion: CCT complexes may promote TC development by affecting the tumor microenvironment thus impacting patient prognosis, potentially serving as a target for the diagnosis and immunotherapy of refractory TC.
Objective: To investigate the expression of eight subunits of chaperonin containing t-complex 1 (CCT) in thyroid cancer (TC) tissues and their correlation with TC staging, patient prognosis, immune cell infiltration, immune checkpoint expression, and chemotherapy drug sensitivity. Methods: Data from The Cancer Genome Atlas (TCGA) database were used to analyze the expression of each CCT subunit in TC tissues and para-cancerous tissues as well as their relationship with the prognosis of TC patients. The biological function of each CCT subunit was analyzed by the Gene Set Enrichment Analysis (GSEA). Data from the TCGA and TIMER2.0 databases were used to analyze the correlations between the expression of each CCT subunit and the tumor microenvironment, infiltration of immune cells, chemotherapeutic drug sensitivity, and immune checkpoint expression. Results: Database analysis showed high mRNA expression of CCT3, CCT7, and CCT8 and low mRNA expression of CCT1, CCT2, CCT5, and CCT6B in TC tissues (P < 0.01 or P < 0.001). CCT3, CCT6B, and CCT8 mRNA expression were correlated with T staging (P < 0.05 or P < 0.01); CCT6B mRNA expression was associated with lymph node metastasis (P < 0.01); CCT5 mRNA expression was associated with distant metastasis (P < 0.05); and CCT6B may serve as an independent prognostic biomarker for overall survival (OS) in TC patients. CCT subunit expression was primarily enriched in signaling pathways such as graft rejection, complement, and interferongamma.Low expression groups of CCT subunits demonstrated significantly higher TC stromal score, immune infiltration score and composite score than the high expression groups (P < 0.05 or P < 0.01 or P < 0.001), displaying a negative correlation between the expression of each CCT subunit and TC stromal, immune infiltration and composite scores (all P < 0.01). The mRNA expression of each CCT subunit was positively correlated with CD8+ T cell and macrophage infiltration (all P < 0.05), the mRNA expression of most CCT subunits (except CCT6B and CCT7) was positively correlated with neutrophil infiltration (P < 0.05 or P < 0.01 or P < 0.001), whereas the mRNA expression of CCT3, 4, 7, and 8 was negatively correlated with CD4+ T-cell infiltration (all P < 0.05). Compared to the low-expression group, patients with high mRNA expression of most CCT subunit had significantly higher IC50 for chemotherapeutic agents such as sorafenib, levatinib, darafenib, trametinib, vandetanib, and cabozantinib (all P < 0.05 or P < 0.01 or P < 0.001). CCT subunit expression in TC tissues was significantly correlated with the expression of PD-1, PD-L1, PD-L2, CTLA4, CD80, and CD86 (P < 0.05 or P < 0.01 or P < 0.001). Conclusion: CCT complexes may promote TC development by affecting the tumor microenvironment thus impacting patient prognosis, potentially serving as a target for the diagnosis and immunotherapy of refractory TC.
2024, 31(9):907-912.
DOI: 10.3872/j.issn.1007-385X.2024.09.009
Abstract:
Objective: To evaluate the clinical efficacy and safety of tumor-specific individualized multi-target autologous dendritic cells (DC)-cytokine-induced killer cells (CIK) in patients with advanced primary liver cancer (PLC). Methods: The clinical data of 119 patients with advanced PLC who received DC-CIK therapy in the Oncology Department of the General Hospital of the Eastern Theater Command from October 2019 to September 2021 were retrospectively analyzed. Patients were divided into two groups based on the type of antigen used to load DCs during treatment: the pDC-CIK group (n = 21) that used patient-specific polypeptide loaded DCs and the DC-CIK group (n = 98) that used tumor cell lysate-loaded DCs. Clinical data of the two groups before and after treatment were analyzed, including the treatment efficacy and the changes in fetoprotein, lymphocyte subsets, cytokines (IL-2, IFN-γ, TNF-α and IL-6), and adverse reactions. Results: Amont the 119 PLC patients, the objective response rates in both the pDC-CIK and DC-CIK groups were 0%, with disease control rates of 76.1% and 72.4%, respectively (P > 0.05). There was no statistical difference in the levels of CD3+ , CD4+ , CD8+ , CD56+ , CD25+ , CD4+ /CD8+ T lymphocytes between the two groups after treatment (all P > 0.05). However, both groups experienced significantly increased mean levels of IL-2, IFN-γ, TNF-α and IL-6 in peripheral blood after treatment (all P < 0.001). There was no significant difference in the mean levels of IL-2, TNF-α and IL-6 in peripheral blood between the two groups after treatment (all P > 0.05), but the IFN-γ level was significantly higher in the pDC-CIK group than that in the DC-CIK group (P < 0.05). The average survival time of patients in the pDC-CIK group was 59.84 months, which was slightly higher than 46.54 months in the DC-CIK group (P > 0.05). No serious adverse reactions occurred during the treatment. Conclusion: Tumor-specific individualized multi-targeted DC-CIK therapy is safe and effective for PLC patients and can enhance immune function, with a trend toward further benefits compared to tumor cell lysate-loaded DC-CIK therapy.
Objective: To evaluate the clinical efficacy and safety of tumor-specific individualized multi-target autologous dendritic cells (DC)-cytokine-induced killer cells (CIK) in patients with advanced primary liver cancer (PLC). Methods: The clinical data of 119 patients with advanced PLC who received DC-CIK therapy in the Oncology Department of the General Hospital of the Eastern Theater Command from October 2019 to September 2021 were retrospectively analyzed. Patients were divided into two groups based on the type of antigen used to load DCs during treatment: the pDC-CIK group (n = 21) that used patient-specific polypeptide loaded DCs and the DC-CIK group (n = 98) that used tumor cell lysate-loaded DCs. Clinical data of the two groups before and after treatment were analyzed, including the treatment efficacy and the changes in fetoprotein, lymphocyte subsets, cytokines (IL-2, IFN-γ, TNF-α and IL-6), and adverse reactions. Results: Amont the 119 PLC patients, the objective response rates in both the pDC-CIK and DC-CIK groups were 0%, with disease control rates of 76.1% and 72.4%, respectively (P > 0.05). There was no statistical difference in the levels of CD3+ , CD4+ , CD8+ , CD56+ , CD25+ , CD4+ /CD8+ T lymphocytes between the two groups after treatment (all P > 0.05). However, both groups experienced significantly increased mean levels of IL-2, IFN-γ, TNF-α and IL-6 in peripheral blood after treatment (all P < 0.001). There was no significant difference in the mean levels of IL-2, TNF-α and IL-6 in peripheral blood between the two groups after treatment (all P > 0.05), but the IFN-γ level was significantly higher in the pDC-CIK group than that in the DC-CIK group (P < 0.05). The average survival time of patients in the pDC-CIK group was 59.84 months, which was slightly higher than 46.54 months in the DC-CIK group (P > 0.05). No serious adverse reactions occurred during the treatment. Conclusion: Tumor-specific individualized multi-targeted DC-CIK therapy is safe and effective for PLC patients and can enhance immune function, with a trend toward further benefits compared to tumor cell lysate-loaded DC-CIK therapy.
2024, 31(9):913-917.
DOI: 10.3872/j.issn.1007-385X.2024.09.010
Abstract:
Friend白血病插入位点1（FLi-1）是ETS转录因子家族的关键成员，它不仅与肿瘤的发生、发展和转移密切相关，也在 肿瘤免疫调节中扮演重要角色，对于理解宿主免疫系统识别和消灭肿瘤细胞至关重要。本文综述了Fli-1在正常组织和不同肿瘤 组织中的表达特征、分子结构特点和其作为转录激活因子的管家基因调控的下游基因如GATA-1、FOG-1和VEGF等的表达；同 时探讨了Fli-1在促进不同种类肿瘤的发生发展、肿瘤细胞转移和肿瘤相关血管的生成及免疫细胞生长发育过程中的功能意义， 以及Fli-1如何通过调节免疫应答来影响肿瘤发生发展和治疗效果。深入研究、理解Fli-1的生物学功能和在肿瘤中的调控机制， 将可能为肿瘤免疫治疗提供潜在的新靶点，为肿瘤治疗开辟新的途径。
Friend白血病插入位点1（FLi-1）是ETS转录因子家族的关键成员，它不仅与肿瘤的发生、发展和转移密切相关，也在 肿瘤免疫调节中扮演重要角色，对于理解宿主免疫系统识别和消灭肿瘤细胞至关重要。本文综述了Fli-1在正常组织和不同肿瘤 组织中的表达特征、分子结构特点和其作为转录激活因子的管家基因调控的下游基因如GATA-1、FOG-1和VEGF等的表达；同 时探讨了Fli-1在促进不同种类肿瘤的发生发展、肿瘤细胞转移和肿瘤相关血管的生成及免疫细胞生长发育过程中的功能意义， 以及Fli-1如何通过调节免疫应答来影响肿瘤发生发展和治疗效果。深入研究、理解Fli-1的生物学功能和在肿瘤中的调控机制， 将可能为肿瘤免疫治疗提供潜在的新靶点，为肿瘤治疗开辟新的途径。
2024, 31(9):918-923.
DOI: 10.3872/j.issn.1007-385X.2024.09.011
Abstract:
多发性骨髓瘤（MM）是一种恶性血液系统疾病，目前仍无完全治愈的方法。T细胞耗竭是MM的重要特征之一，与 MM的进展、复发以及耐药密切相关。在MM中可以通过多种途径导致T细胞耗竭，主要包括代谢重编程、细胞因子、转录因子以 及肿瘤相关免疫细胞等方式。MM患者中高比例的耗竭性T细胞（Tex细胞）是导致肿瘤细胞免疫逃逸和免疫治疗失败的一个重 要因素。因此，针对Tex细胞的免疫治疗，例如靶向免疫检查点、T细胞相关转录因子和细胞因子等方式可成为MM的新型治疗 方式。本文综述了T细胞耗竭在MM中的研究进展，为进一步了解MM的耐药机制以及开发新的治疗策略提供理论依据。
多发性骨髓瘤（MM）是一种恶性血液系统疾病，目前仍无完全治愈的方法。T细胞耗竭是MM的重要特征之一，与 MM的进展、复发以及耐药密切相关。在MM中可以通过多种途径导致T细胞耗竭，主要包括代谢重编程、细胞因子、转录因子以 及肿瘤相关免疫细胞等方式。MM患者中高比例的耗竭性T细胞（Tex细胞）是导致肿瘤细胞免疫逃逸和免疫治疗失败的一个重 要因素。因此，针对Tex细胞的免疫治疗，例如靶向免疫检查点、T细胞相关转录因子和细胞因子等方式可成为MM的新型治疗 方式。本文综述了T细胞耗竭在MM中的研究进展，为进一步了解MM的耐药机制以及开发新的治疗策略提供理论依据。
2024, 31(9):924-930.
DOI: 10.3872/j.issn.1007-385X.2024.09.012
Abstract:
卷曲蛋白2（Fzd2）是一种很重要的肿瘤标志物，在多肿瘤中均异常表达，参与肿瘤的发生发展过程。Fzd2在肿瘤中的 调控作用与多种Wnt信号通路密切相关。Fzd2和Wnt通路在乳腺癌、肝癌、宫颈癌等多种肿瘤中被过度激活，促进肿瘤细胞的增 殖、侵袭及转移。Fzd2还可以诱导肿瘤细胞获得干性，调节肿瘤干细胞的自我更新和分化，从而促进肿瘤的复发及耐药的增加， 影响肿瘤的治疗效果。Fzd2还参与肿瘤微环境的形成及肿瘤相关血管的生成，进一步促进和加剧了肿瘤的恶化。深入探讨Fzd2 在肿瘤中的调控机制，可为肿瘤治疗提供潜在的新靶点或突破点，为肿瘤的个体化治疗提供新的思路。
卷曲蛋白2（Fzd2）是一种很重要的肿瘤标志物，在多肿瘤中均异常表达，参与肿瘤的发生发展过程。Fzd2在肿瘤中的 调控作用与多种Wnt信号通路密切相关。Fzd2和Wnt通路在乳腺癌、肝癌、宫颈癌等多种肿瘤中被过度激活，促进肿瘤细胞的增 殖、侵袭及转移。Fzd2还可以诱导肿瘤细胞获得干性，调节肿瘤干细胞的自我更新和分化，从而促进肿瘤的复发及耐药的增加， 影响肿瘤的治疗效果。Fzd2还参与肿瘤微环境的形成及肿瘤相关血管的生成，进一步促进和加剧了肿瘤的恶化。深入探讨Fzd2 在肿瘤中的调控机制，可为肿瘤治疗提供潜在的新靶点或突破点，为肿瘤的个体化治疗提供新的思路。
2024, 31(9):931-936.
DOI: 10.3872/j.issn.1007-385X.2024.09.013
Abstract:
宫颈癌是一种发病率和转移率均较高的妇科癌症。尽管手术、放射、化学治疗在宫颈癌治疗中取得了显著的临床效 果，但仍存在一定的局限性，因此亟需新的治疗药物。近年研究发现，Wnt/β-catenin 信号通路在宫颈癌发生发展、转移、耐药等过 程中起关键性作用。Wnt/β-catenin信号途径参与宫颈癌的发生发展和远处转移及对化疗药物的耐受性；天然化合物如中药白藜 芦醇和黄芩素等及合成化合物如伊曲康唑等均可通过此信号通路发挥抗宫颈癌的作用；非编码RNA和一些蛋白分子均可以通 过此通路影响宫颈癌的发生发展。研究说明，Wnt/β-catenin 信号途径是宫颈癌治疗的潜在靶点。本文归纳宫颈癌中 Wnt/β -catenin信号途径的作用，以期为宫颈癌的临床研究与新药开发提供参考依据。
宫颈癌是一种发病率和转移率均较高的妇科癌症。尽管手术、放射、化学治疗在宫颈癌治疗中取得了显著的临床效 果，但仍存在一定的局限性，因此亟需新的治疗药物。近年研究发现，Wnt/β-catenin 信号通路在宫颈癌发生发展、转移、耐药等过 程中起关键性作用。Wnt/β-catenin信号途径参与宫颈癌的发生发展和远处转移及对化疗药物的耐受性；天然化合物如中药白藜 芦醇和黄芩素等及合成化合物如伊曲康唑等均可通过此信号通路发挥抗宫颈癌的作用；非编码RNA和一些蛋白分子均可以通 过此通路影响宫颈癌的发生发展。研究说明，Wnt/β-catenin 信号途径是宫颈癌治疗的潜在靶点。本文归纳宫颈癌中 Wnt/β -catenin信号途径的作用，以期为宫颈癌的临床研究与新药开发提供参考依据。
2024, 31(9):937-939.
DOI: 10.3872/j.issn.1007-385X.2024.09.014
Abstract:
肿瘤免疫学是临床医学学术学位研究生科研方向的热点，然而，本科阶段肿瘤免疫学课程内容与科研训练的缺陷严 重影响研究生科研课题的开展。本教学组以临床医学研究生进行肿瘤免疫学研究的“岗位胜任力”为导向，以“先进性、实用性、 可及性”为原则，配合科研诚信与医学伦理教育，从多个角度探索培养临床医学研究生的肿瘤免疫学科研思维与技术的有效路 径。通过调查问卷的形式对课程效果进行评估，结果表明，此次肿瘤免疫学研究生实验课程建设取得了良好的教学效果。
肿瘤免疫学是临床医学学术学位研究生科研方向的热点，然而，本科阶段肿瘤免疫学课程内容与科研训练的缺陷严 重影响研究生科研课题的开展。本教学组以临床医学研究生进行肿瘤免疫学研究的“岗位胜任力”为导向，以“先进性、实用性、 可及性”为原则，配合科研诚信与医学伦理教育，从多个角度探索培养临床医学研究生的肿瘤免疫学科研思维与技术的有效路 径。通过调查问卷的形式对课程效果进行评估，结果表明，此次肿瘤免疫学研究生实验课程建设取得了良好的教学效果。
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- 《中国肿瘤生物治疗杂志》
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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.