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Chinese Journal of Oncology Prevention and Treatment

Table of Content

    25 October 2023, Volume 15 Issue 5 Previous Issue    Next Issue
    Expert consensus on the diagnosis and treatment of midline (NUT) carcinoma (2023 Edition)
    NUT Carcinoma Diagnosis Working Group of the Chinese Anti-Cancer Association's Oncogene Diagnosis
    2023, 15 (5):  463-476.  doi: 10.3969/j.issn.1674-5671.2023.05.01
    Abstract ( 1478 )   PDF   Save
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    Progress of chemotherapy for cervical cancer 
    WU Daying, JIANG Yao, LI Guiling
    2023, 15 (5):  492-498.  doi: 10.3969/j.issn.1674-5671.2023.05.04
    Abstract ( 696 )   PDF   Save
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    Progress of chemotherapy for vaginal malignant tumors 
    LIU Linying, GUO Ciren, SUN Yang
    2023, 15 (5):  499-503.  doi: 10.3969/j.issn.1674-5671.2023.05.05
    Abstract ( 688 )   PDF   Save
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    Chemotherapy of uterine sarcoma and its prospect
    LIU Chuan, LI Xiuqin
    2023, 15 (5):  504-509.  doi: 10.3969/j.issn.1674-5671.2023.05.06
    Abstract ( 741 )   PDF   Save
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    Metformin inhibits proliferation and migration of esophageal squamous cancer cells by regulating Gas6/Axl signaling pathway
    CHEN Hongyu, NING Shoubin, CHEN Xiao, LI Manhua, XU Mengnan, LI Bairong, LI Hui, LI Jing, YU Yan, FAN Chongxi
    2023, 15 (5):  516-524.  doi: 10.3969/j.issn.1674-5671.2023.05.08
    Abstract ( 114 )   PDF   Save
    Objective To investigate the inhibitory effect of metformin on the proliferation and migration of esophageal squamous cell carcinoma, and the regulatory mechanism of the growth⁃arrest⁃specific 6 (Gas6) and its ligand Axl. Methods The EC109 and TE⁃1 cells of esophageal squamous cell carcinoma were treated with different concentrations of metformin. The cell proliferation was measured by the CCK⁃8 assay or the plate clone formation. The migration ability was detected by wound healing and transwell migration assays. Apoptosis was detected by TUNEL assay and the mitochondrial oxidative stress state was detected by Mito⁃SOX. The revealed mitochondrial membrane potential (MMP) was measured by JC⁃1 staining. The expression of Gas6 was detected by immunofluorescence and by the changes of the Gas6/Axl pathway and apoptosis⁃related proteins were analyzed using Western blot. In addition, after treatment with Axl inhibitor (bemcentinib, R428), the effect of metformin on the proliferation, migration of EC109 cells, and subcutaneous tumor formation in nude mice were observed. Results Metformin significantly decreased the cell viability of EC109 and TE⁃1 cells compared to the control group ( PEC109<0.001; PTE⁃1<0.001) , while the effect was not significant on the activity of Het⁃1A cells (P=0.380). Metformin inhibited the colony formation (P=0.002) and migration (P<0.001) of EC109 cells, and increased the apoptosis rate (P=0.002), inducing a dose⁃dependent increase in mitochondrial reactive oxygen species (P<0.001) and decreasing MMP levels (P<0.001). Furthermore, Metformin reduced Gas6 fluorescence intensity in EC109 cells, blocked Gas6 expression in EC109 and TE⁃1 cells, down⁃regulated the levels of p⁃Axl, Axl and Bcl2 in EC109 cells, and increased the activities of Bax, cytochrome C and Caspase3 in EC109 cells. In addition, compared with metformin alone, metformin combined with R428 demonstrated superior efficacy in inhibiting tumor growth, migration and subcutaneous tumor formation in nude mice. Conclusions Metformin can regulate mitochondrial homeostasis, activate an oxidative stress⁃induced apoptotic response, and exert anti⁃proliferative and anti⁃migrative effects on EC109 cells, which may be associated with the down⁃regulation of Gas6/Axl signaling pathway.
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    Effects of LGR4 on proliferation,apoptosis,invasion,migration and epithelial mesenchymal transformation of nasopharyngeal carcinoma cells
    ZHOU Yufei, LI Kaiguo, YANG Xiaohui, CHEN Xuxia, CHEN Weiling, QU Song
    2023, 15 (5):  525-532.  doi: 10.3969/j.issn.1674-5671.2023.05.09
    Abstract ( 178 )   PDF   Save
    Objective To investigate the effects of Leucine⁃rich repeats containing G protein⁃coupled receptor 4 (LGR4) on the proliferation, apoptosis, invasion, migration and epithelial mesenchymal transition (EMT) of nasopharyngeal carcinoma (NPC) cell lines C666⁃1. Methods The differential genes were obtained by intersection of GEO database sequencing data GSE89804, GSE15903 and GSE103611 using Venn diagram. The expression of LGR4 in NPC tissues, corresponding normal tissues，NPC tumor tissues with and without distant metastasis were analyzed by the bioinformatic analysis. The expression levels of LGR4 in NPC cell lines C666⁃1 and normal nasopharyngeal cell lines NP69 were detected by RT⁃qPCR and Western blot. NPC cell lines C666⁃1 were divided into the NC group ( negative control lentivirus), the KD1 group and the KD2 group (Knock Down). The expression of LGR4 and epithelial marker E⁃cadherin were detected by Western blot. Cell proliferation, apoptosis, invasion and migration were detected by CCK⁃8, clone formation assays, flow cytometry, scratch assay and Transwell assay. Results Venn diagram showed that the differential gene of GSE89804, GSE15903 and GSE103611 data sets was LGR4. The results of GSE12452 dataset showed that the LGR4 was up⁃regulated in NPC tissues by constrast with corresponding normal tissues (P<0.05). The results of GSE103611 dataset showed that the LGR4 was up⁃regulated in NPC tumor tissues with distant metastasis by contrast with NPC tumor tissues without distant metastasis (P<0.05). Compared with the mRNA and protein expression levels of NP69 cell lines, those of LGR4 were significantly up⁃regulated in NPC cell lines C666⁃1 (all P<0.001). Compared with the NC group, the knockdown of LGR4 inhibited the proliferation (all P<0.05), invasion and migration (all P<0.001), and promoted the apoptosis and protein expression of E⁃cadherin in C666⁃1 cell lines (all P<0.001). Conclusions  The expression of LGR4 is up⁃regulated in NPC cell lines C666⁃1. The knockdown of LGR4 could inhibit the proliferation, invasion, migration and promote apoptosis and EMT of NPC cell lines C666⁃1.
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     Galectin-4 regulates PD-L1 and affects the function of CD8+T cells in killing liver cancer cells
    WEI Xiaohuan, SHAN Qianqian, LIU Yuanyuan
    2023, 15 (5):  532-537.  doi: 10.3969/j.issn.1674-5671.2023.05.10
    Abstract ( 134 )   PDF   Save
    Objective To investigate the effect of human Galectin⁃4 (Gal⁃4) on CD8+T cells killing liver cells and its mechanism. Methods The human peripheral blood CD8+T cells and dendritic cells (DC) were extracted and identified. Normal human liver cells WRL68 and liver cancer cells including HepG2, SMMC⁃7721, Hep3B and Huh⁃7 were selected, and Western blot was used to detect the expression of Gal⁃4 protein. The liver cancer cells HepG2 and SMMC⁃7721 were transfected with Gal⁃4 siRNA and negative control (the si⁃Gal⁃4 group and si⁃NC group) using Lipofectamine 3000. The HepG2 and SMMC⁃7721 cells in the si⁃Gal⁃4 and si⁃NC groups were co⁃incubated with DC⁃activated CD8+T cells for 18 hours (the si⁃Gal⁃4/HepG2+CD8+T group, si⁃NC/HepG2+CD8+T group, si⁃Gal⁃4/SMMC⁃7721+CD8+T group, si⁃NC/SMMC⁃7721+CD8+T group). Cytotoxicity experiments were performed to evaluate the capability of CD8+T cells in killing the tumor cells in each group, and enzyme⁃linked immunosorbent assay (ELISA) was used to detect the levels of interferon ⁃γ (INF⁃ γ) and tumor necrosis factor⁃α (TNF⁃α) in the cell supernatants of each group. Western blot was used to detect the expression of PD⁃L1 protein in the tumor cells of each group. Results Compared with normal liver cell WRL68, the expression of Gal⁃4 protein were significantly up⁃regulated in liver cancer cells HepG2, SMMC⁃7721, Hep3B, and Huh⁃7 (all P<0.001). Compared with the si⁃NC/HepG2+CD8+T group or si⁃NC/SMMC⁃7721+CD8+T group, the killing ability of si⁃Gal⁃4/HepG2+CD8+T group and the si⁃Gal⁃4/SMMC⁃7721+CD8+T group were significant increased (all P<0.001). After inhibiting the expression of Gal⁃4, the concentrations of INF⁃γ and TNF⁃α in co⁃culture system were significantly increased (all P<0.001). Compared with the si⁃NC group, the expression of PD⁃L1 protein in HepG2 and SMMC⁃7721 cells of si⁃Gal⁃4 group were significantly down⁃regulated (P<0.001). Conclusions Gal⁃4 is highly expressed in liver cancer cells, and inhibition of Gal⁃4 may down⁃regulate the expression of PD⁃L1 in liver cancer cells and promote the killing ability of CD8+T cells.
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    A trend analysis of the incidence and mortality of lung cancer and an age-period-cohort model in China,1990—2019 
    QIU Haiping, XIE Xiaoping, CHEN Tianqing
    2023, 15 (5):  537-542.  doi: 10.3969/j.issn.1674-5671.2023.05.11
    Abstract ( 382 )   PDF   Save
    Objective To analyze the trends of the incidence and mortality of lung cancer in China from 1990 to 2019, providing a scientific basis for the prevention and treatment of lung cancer in China. Methods The incidence and mortality data of lung cancer in China from 1990 to 2019 were obtained from the Global Burden of Disease database, and used to analyze the changes of lung cancer by Joinpoint regression model. The age⁃period⁃cohort model was established using Stata 17 software for analyzing the changes in lung cancer under the influence of age, period, and cohort factors. Results From 1990 to 2019, the incidence and mortality of lung cancer in the Chinese female, male and the general population showed a gradual upward trend, with an average annual percent change (AAPC) value of 1.176% for the incidence and 0.786% for the mortality. The age effect coefficient for incidence in the Chinese population increased from -152.224 to 229.609, and the period effect coefficient increased from -16.116 to 22.409, with the highest effect coefficient of 65.753 for the 1951 birth cohort; the age group effect coefficient for death in the Chinese population increased from -167.360 to 286.438, and the period effect coefficient increased from -14.792 to 21.162. The cohort effect coefficient of death was the highest in the birth cohort from 1951 to 1956, and the effect coefficient was 69.846. Conclusion The overall incidence and mortality of lung cancer in China showed an upward trend from 1990 to 2019, and both age and period are important factors affecting the occurrence and development of lung cancer in the population. Both the incidence and mortality risks of the cohort, born in between 1951 and 1956, are at the highest level, and prevention and treatment should be focused on this group of people to reduce their disease burden.
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    The clinical value of inflammatory burden index in the diagnosis and prognosis of colorectal cancer
    ZHU Lin, LU Ning, YANG Lin, WEN Hua, CUI Manli, ZHANG Mingxin
    2023, 15 (5):  543-548.  doi: 10.3969/j.issn.1674-5671.2023.05.12
    Abstract ( 169 )   PDF   Save
    Objective To investigate the clinical value of the inflammatory burden index (IBI) in the diagnosis and prognosis of colorectal cancer. Methods A total of 350 patients with colorectal cancer diagnosed pathologically in the First Affiliated Hospital of Xi'an Medical University from January 2017 to January 2022 were selected as the study subjects, and 350 healthy individuals who underwent physical examinations during the same period were selected as the control group. The receiver operating characteristic(ROC) was used to analyze the value of IBI in the diagnosis and prognosis prediction of colorectal cancer. Univariable and multivariable Cox regression models were used to analyze the associations of IBI and clinical indicators with prognosis of colorectal cancer. A nomogram was established to predict the survival rate. Results The ROC curve analysis showed that IBI was statistically significant in the diagnosis of colorectal cancer (Z=12.382, P<0.001). The area under the curve (AUC) was 0.813 (95%CI: 0.774-0.848), and the best cut⁃off point was 25.52. IBI was also statistically significant in predicting the prognosis of colorectal cancer (Z=9.473, P<0.001). The AUC was 0.824 (95%CI: 0.771-0.869), and the best cut⁃off point was 33.68. Univariable Cox regression analysis showed that higher IBI was correlated with higher preoperative CEA and worse T and N staging (P<0.05). Multivariable Cox regression analysis showed that IBI>33.68 was an independent risk factor affecting the prognosis of colorectal cancer patients(HR=3.576, 95%CI: 3.114-4.138). The overall C⁃index of the nomogram model was 0.849 (95%CI: 0.829-0.868, P<0.001). The calibration curve showed good consistency between the predicted survival rate and the actual survival rate. Conclusions IBI >33.68 is an independent prognostic risk factor for colorectal cancer. IBI has good diagnostic and prognostic value and may be a new biomarker for colorectal cancer.
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    Prediction model of high-risk population of upper gastrointestinal cancer and precancerous lesions
    ZHANG Zhihong, CUI Wangfei, WANG Xinzheng, CAO Ling, ZHANG Yongzhen
    2023, 15 (5):  549-555.  doi: 10.3969/j.issn.1674-5671.2023.05.13
    Abstract ( 139 )   PDF   Save
    Objective To analyze the risk factors of upper gastrointestinal cancer and precancerous lesions, to construct a prediction model for high⁃risk population of upper gastrointestinal cancer, and to identify high⁃risk groups of upper gastrointestinal cancer. Methods The population group at age 40-69 who participated in the "Rural Upper Gastrointestinal Cancer Early Diagnosis and Treatment Project " in Yangcheng County, Shanxi Province from June 2020 to December 2021 were selected, and randomly divided into a training set (n=1,997) and a validation set (n=852), according to the inclusion and exclusion criteria with a ratio of 7 to 3, used for training and validation of the model, respectively. The chi⁃square test was used for univariate analysis, the factors with P < 0.2 were screened for the optimal subset of variables, and the combination of variables with the lowest akaike information criterion (AIC) was selected to construct a logistic regression model and establish a scoring scale. The receiver operating characteristic curve (ROC) was drawn and the discrimination of the model was evaluated according to the area under the curve (AUC). The calibration of the model was evaluated by the Hosmer⁃Lemeshow (H⁃L) test and the calibration curve. The clinical decision curve analysis (DCA) was used to evaluate the clinical applicability. Results A logistic regression prediction model for the high⁃risk population of upper gastrointestinal cancer and precancerous lesions was established based on five risk factors, including age, sex, smoking, hot food intake and family history of cancer. The AUCs of the training set and the validation set of the model were 0.759 (95%CI: 0.689-0.830) and 0.743 (95%CI: 0.606-0.880), respectively. The calibration curve combined with H⁃L test proved that the model had good calibration (P>0.05). According to the logistic regression model, a scoring scale model was established with a score ranging from 0 to 27 points. The higher the score, the higher the risk of disease. The AUCs of the training set and the validation set were 0.760 (95%CI: 0.690-0.829) and 0.748 (95%CI: 0.612-0.884), respectively. The calibration curve combined with the H⁃L test proved that the model had good calibration (P>0.05).The DCA indicated that the model had good clinical applicability. Conclusions The prediction model and scoring scale model of the high⁃risk population of upper gastrointestinal cancer and precancerous lesions, based on the five risk factors including age, sex, smoking, hot food intake and family history of cancer, have good predictive value, which are helpful for the screening of the upper gastrointestinal cancer population.
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    Role and clinical significance of androgen receptor-related gene scoring system in prognostic prediction of bladder cancer
    MO Han, LIU Hui, FENG Chao, XIE Yuanliang, WANG Qiuyan, LI Tianyu
    2023, 15 (5):  556-563.  doi: 10.3969/j.issn.1674-5671.2023.05.14
    Abstract ( 117 )   PDF   Save
     Objective To construct a scoring system for androgen receptors (AR)⁃related genes in bladder cancer and to explore the characteristics of the tumour microenvironment in bladder cancer patients with different AR scores. Methods Based on the TCGA⁃BLCA cohort, the scoring system was constructed based on the set of AR⁃related genes reported in the literature, and validated in the GSE⁃13507 cohort and 29 self⁃owned clinical samples of bladder cancer. Transcriptomics and high⁃throughput single⁃cell mass spectrometry flow⁃acquisition techniques were applied to reveal molecular features and tumour microenvironmental heterogeneity of bladder cancer patients in the high and low AR score groups. Results An AR⁃related gene scoring system for bladder cancer was constructed based on the TCGA⁃BLCA cohort. The results of the TCGA⁃BLCA cohort and GSE⁃13507 cohort analyses showed that the overall survival (OS) of bladder cancer patients in the high AR score group was significantly worse than that in the low AR score group (P=0.009, 0.010). Although the results of the clinical sample analyses were not statistically significant, the OS of patients in the high AR score group was worse than that in the low AR score group (P=0.180), and patients in the high AR score group had later clinical stage and higher pathological grading. The patients in the low and high AR score groups had different molecular profiles, with heterogeneous tumour microenvironments, and enriched in the high AR score group were immunosuppressive CD4+ T⁃cell subpopulation 13 and characteristic tumour stem⁃like cell subpopulation 13 with an immunosuppressive phenotype. Conclusions A scoring system for AR⁃related genes was constructed in this study, in which patients in the high AR scoring group had a poorer prognosis than that in the low AR score group, and patients in the high AR score group had more severe immunosuppressive state of the tumour microenvironment, probably showing higher response to immunotherapy, and becoming more suitable for immunotherapy.
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    Analysis of the risk factors of anastomotic leakage after total laparoscopic transrectal specimen extraction surgery (NOSES Ⅳ) for colorectal cancer
    LI Wei, LIU Ligang, YANG Junquan, LIU Chun, ZHANG Zhixue, GAO Fuchun, ZHANG Caixia, LIU Shuhong, LI Xinyu
    2023, 15 (5):  564-569.  doi: 10.3969/j.issn.1674-5671.2023.05.15
    Abstract ( 123 )   PDF   Save
    Objective To investigate the risk factors of anastomotic leakage after total laparoscopic transanal natural orifice specimen extraction surgery (NOSES Ⅳ) for colorectal cancer. Methods The clinicopathological data of 268 patients with colorectal cancer who underwent NOSES Ⅳ in the Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College and Luanzhou People's Hospital from January 2016 to June 2023 were retrospectively analyzed. Patients were divided into the anastomotic leakage group (n=27) and the non⁃anastomotic leakage group (n=241) according to the occurrence of anastomotic leakage. The risk factors were analyzed by both univariable and multivariable logistic regressions. Results The incidence of anastomotic leakage after NOSES Ⅳ for colorectal cancer was 10.1%. The univariable analysis showed that the male patients with tumor distance <8 cm from anal margin and operation time ≥140 min were associated with anastomotic leakage. The multivariable logistic regression analysis showed that a duration of operation ≥140 min was an independent influential factor of postoperative anastomotic leakage in patients who underwent NOSES Ⅳ for colorectal cancer (OR=5.987, 95%CI: 1.519-23.602, P=0.011) Conclusions Operation time is a influential factor for anastomotic leakage after NOSES Ⅳ for colorectal cancer.
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    Research progress of biological clock gene Bmal1 in tumor 
    GUO Enhui, CHENG Bing, FENG Siqi, MA Ting
    2023, 15 (5):  570-575.  doi: 10.3969/j.issn.1674-5671.2023.05.16
    Abstract ( 289 )   PDF   Save
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     Research progress in the regulation of non-coding RNA by ginsenoside for anti-tumor
    LI Meile, JIN Kai, TANG Ting, GUO Ju, ZHAO Ziyue, Xie Yu'an
    2023, 15 (5):  576-580.  doi: 10.3969/j.issn.1674-5671.2023.05.17
    Abstract ( 124 )   PDF   Save
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    Tumor microenvironment regulates the mechanism of HER2-targeted drug resistance in breast cancer and its reversal strategy
    GAO Xiaomin, GUO Xu, WANG Ling, YANG Rui, JIANG Sunmin, YUAN Wenbo, YAO Ying
    2023, 15 (5):  581-586.  doi: 10.3969/j.issn.1674-5671.2023.05.18
    Abstract ( 149 )   PDF   Save
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