Jiming Chen, Yinhang Wu, Qing Zhou, Yifei Song, Jing Zhuang, Kongjie Lu, Xi Yang
{"title":"GPX3 是一个与胆固醇相关的关键基因,与结直肠癌的预后和肿瘤浸润 T 细胞有关。","authors":"Jiming Chen, Yinhang Wu, Qing Zhou, Yifei Song, Jing Zhuang, Kongjie Lu, Xi Yang","doi":"10.4149/neo_2023_230704N348","DOIUrl":null,"url":null,"abstract":"<p><p>High cholesterol is an important factor inducing colorectal cancer (CRC). The study aims to determine the key genes and regulatory mechanism associated with tumor-infiltrating T cells underlying cholesterol-induced CRC. Gene expression data and clinical data from CRCS in The Cancer Genome Atlas (TCGA) were selected for differential expression and survival analysis. A total of 5,815 DEGs and 21 cholesterol-associated KEGG pathways were identified. Subsequently, 128 CRCs and 127 patients without obvious intestinal lesions were recruited to analyze the relationship between GPX3 expression, cholesterol levels, and pathologic condition. The results showed that the expression of cholesterol-related gene GPX3 was negatively associated with cholesterol level, but positively correlated with Ki-67 proliferation index in CRC. The expression of GPX3 was higher in CRC patients who were in poorly differentiated and advanced stage. In addition, a mice model of high-cholesterol diet intervention was constructed to detect the levels of cholesterol and GPX3 in the peripheral blood of mice, and it was found that the expression level of GPX3 in high-cholesterol mice was lower than that in normal diet mice. CD8+ T cells were isolated from the spleen of mice and the T cell surface receptors were detected. It was found that the expression of CD69 in CD8+ T cells of mice interfered with the high-cholesterol diet, while the expression of PD1, TIM-3, and CTLA-4 was increased. CD8+ T cells were co-cultured with MC38 cells to detect the proliferation rate of CRC cells. The results showed that the tumor cell proliferation ratio in the high cholesterol group was higher than that in the control group. Furthermore, GPX3 downstream genes associated with m6A modification and tumor-infiltrating T cells were screened, and a T cell immune-related ceRNA network was constructed. In total, 53 GPX3 downstream genes associated with m6A modification and tumor-infiltrating T cells were identified. A PPI network that contained 45 nodes and 85 interaction pairs was constructed. The ceRNA network, including 39 miRNA-target and 43 lncRNA-miRNA regulatory pairs, was constructed. In conclusion, GPX3 is a potential target for cholesterol regulation of T cell immunity in CRC.</p>","PeriodicalId":19266,"journal":{"name":"Neoplasma","volume":"70 5","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GPX3 is a key cholesterol-related gene associated with prognosis and tumor-infiltrating T cells in colorectal cancer.\",\"authors\":\"Jiming Chen, Yinhang Wu, Qing Zhou, Yifei Song, Jing Zhuang, Kongjie Lu, Xi Yang\",\"doi\":\"10.4149/neo_2023_230704N348\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>High cholesterol is an important factor inducing colorectal cancer (CRC). The study aims to determine the key genes and regulatory mechanism associated with tumor-infiltrating T cells underlying cholesterol-induced CRC. Gene expression data and clinical data from CRCS in The Cancer Genome Atlas (TCGA) were selected for differential expression and survival analysis. A total of 5,815 DEGs and 21 cholesterol-associated KEGG pathways were identified. Subsequently, 128 CRCs and 127 patients without obvious intestinal lesions were recruited to analyze the relationship between GPX3 expression, cholesterol levels, and pathologic condition. The results showed that the expression of cholesterol-related gene GPX3 was negatively associated with cholesterol level, but positively correlated with Ki-67 proliferation index in CRC. The expression of GPX3 was higher in CRC patients who were in poorly differentiated and advanced stage. In addition, a mice model of high-cholesterol diet intervention was constructed to detect the levels of cholesterol and GPX3 in the peripheral blood of mice, and it was found that the expression level of GPX3 in high-cholesterol mice was lower than that in normal diet mice. CD8+ T cells were isolated from the spleen of mice and the T cell surface receptors were detected. It was found that the expression of CD69 in CD8+ T cells of mice interfered with the high-cholesterol diet, while the expression of PD1, TIM-3, and CTLA-4 was increased. CD8+ T cells were co-cultured with MC38 cells to detect the proliferation rate of CRC cells. The results showed that the tumor cell proliferation ratio in the high cholesterol group was higher than that in the control group. Furthermore, GPX3 downstream genes associated with m6A modification and tumor-infiltrating T cells were screened, and a T cell immune-related ceRNA network was constructed. In total, 53 GPX3 downstream genes associated with m6A modification and tumor-infiltrating T cells were identified. A PPI network that contained 45 nodes and 85 interaction pairs was constructed. The ceRNA network, including 39 miRNA-target and 43 lncRNA-miRNA regulatory pairs, was constructed. In conclusion, GPX3 is a potential target for cholesterol regulation of T cell immunity in CRC.</p>\",\"PeriodicalId\":19266,\"journal\":{\"name\":\"Neoplasma\",\"volume\":\"70 5\",\"pages\":\"\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neoplasma\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4149/neo_2023_230704N348\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neoplasma","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4149/neo_2023_230704N348","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
高胆固醇是诱发结直肠癌(CRC)的一个重要因素。本研究旨在确定胆固醇诱导 CRC 的关键基因和与肿瘤浸润 T 细胞相关的调控机制。研究选取了癌症基因组图谱(TCGA)中CRCS的基因表达数据和临床数据进行差异表达和生存分析。共鉴定出 5,815 个 DEGs 和 21 个胆固醇相关 KEGG 通路。随后,研究人员招募了 128 例 CRC 和 127 例无明显肠道病变的患者,分析 GPX3 表达、胆固醇水平和病理状况之间的关系。结果显示,胆固醇相关基因GPX3的表达与胆固醇水平呈负相关,但与CRC的Ki-67增殖指数呈正相关。在分化较差和晚期的 CRC 患者中,GPX3 的表达量更高。此外,还构建了高胆固醇饮食干预小鼠模型,检测小鼠外周血中胆固醇和 GPX3 的水平,结果发现高胆固醇小鼠 GPX3 的表达水平低于正常饮食小鼠。从小鼠脾脏中分离出 CD8+ T 细胞,并检测 T 细胞表面受体。结果发现,高胆固醇饮食会影响小鼠 CD8+ T 细胞中 CD69 的表达,而 PD1、TIM-3 和 CTLA-4 的表达则会增加。CD8+ T细胞与MC38细胞共培养,检测CRC细胞的增殖率。结果显示,高胆固醇组的肿瘤细胞增殖率高于对照组。此外,研究人员还筛选了与m6A修饰和肿瘤浸润T细胞相关的GPX3下游基因,并构建了T细胞免疫相关的ceRNA网络。总共发现了53个与m6A修饰和肿瘤浸润T细胞相关的GPX3下游基因。构建了一个包含 45 个节点和 85 对相互作用的 PPI 网络。构建的ceRNA网络包括39个miRNA-靶标和43个lncRNA-miRNA调控对。总之,GPX3是胆固醇调控CRC中T细胞免疫的潜在靶点。
GPX3 is a key cholesterol-related gene associated with prognosis and tumor-infiltrating T cells in colorectal cancer.
High cholesterol is an important factor inducing colorectal cancer (CRC). The study aims to determine the key genes and regulatory mechanism associated with tumor-infiltrating T cells underlying cholesterol-induced CRC. Gene expression data and clinical data from CRCS in The Cancer Genome Atlas (TCGA) were selected for differential expression and survival analysis. A total of 5,815 DEGs and 21 cholesterol-associated KEGG pathways were identified. Subsequently, 128 CRCs and 127 patients without obvious intestinal lesions were recruited to analyze the relationship between GPX3 expression, cholesterol levels, and pathologic condition. The results showed that the expression of cholesterol-related gene GPX3 was negatively associated with cholesterol level, but positively correlated with Ki-67 proliferation index in CRC. The expression of GPX3 was higher in CRC patients who were in poorly differentiated and advanced stage. In addition, a mice model of high-cholesterol diet intervention was constructed to detect the levels of cholesterol and GPX3 in the peripheral blood of mice, and it was found that the expression level of GPX3 in high-cholesterol mice was lower than that in normal diet mice. CD8+ T cells were isolated from the spleen of mice and the T cell surface receptors were detected. It was found that the expression of CD69 in CD8+ T cells of mice interfered with the high-cholesterol diet, while the expression of PD1, TIM-3, and CTLA-4 was increased. CD8+ T cells were co-cultured with MC38 cells to detect the proliferation rate of CRC cells. The results showed that the tumor cell proliferation ratio in the high cholesterol group was higher than that in the control group. Furthermore, GPX3 downstream genes associated with m6A modification and tumor-infiltrating T cells were screened, and a T cell immune-related ceRNA network was constructed. In total, 53 GPX3 downstream genes associated with m6A modification and tumor-infiltrating T cells were identified. A PPI network that contained 45 nodes and 85 interaction pairs was constructed. The ceRNA network, including 39 miRNA-target and 43 lncRNA-miRNA regulatory pairs, was constructed. In conclusion, GPX3 is a potential target for cholesterol regulation of T cell immunity in CRC.