脂肪酸分解代谢相关基因ABHD1和PLA2G15在结直肠癌不良预后及肿瘤进展中的研究  

Role of fatty acid catabolism related genes ABHD1 and PLA2G15 predicting poor prognosis and promoting tumor progression in colorectal cancer

作　　者：王文鹏 邓露 施丹 胡均 王捷夫 云铎 孔大陆 Wenpeng Wang;Lu Deng;Dan Shi;Jun Hu;Jiefu Wang;Duo Yun;Dalu Kong(Department of Colorectal Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin’s Clinical Research Center for Cancer,Tianjin Key Laboratory of Digestive Cancer,Tianjin 300060,China;Department of Gynecological Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Department of Gastrointestinal Surgery,Tianjin Nan Kai Hospital,Tianjin Medical University,Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair,Institute of Integrative Medicine for Acute Abdominal Diseases,Tianjin 300100,China;Department of Oncology,the First Hospital of Hohhot,Hohhot 010020,China)

机构地区：[1]天津医科大学肿瘤医院结直肠肿瘤科,国家恶性肿瘤临床医学研究中心,天津市恶性肿瘤临床医学研究中心,天津市消化系统肿瘤重点实验室,300060 [2]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院妇瘤科,北京100021 [3]天津医科大学南开临床学院胃肠外科,天津市急腹症器官损伤与中西医修复重点实验室,天津市中西医结合急腹症研究所,300100 [4]呼和浩特市第一医院肿瘤科,010020

出　　处：《中华结直肠疾病电子杂志》2024年第2期101-111,共11页Chinese Journal of Colorectal Diseases(Electronic Edition)

基　　金：国家自然科学基金(82373134);天津市教委科研计划基金(2022KJ228);中国抗癌协会-恒瑞抗血管生成靶向肿瘤研究基金(2021001045);天津医科大学肿瘤医院国家自然科学基金培育计划(220108);天津大学温州安全(应急)研究院科研转化基金(TJUWYYY2022025);天津市医学重点学科(与科)建设项目(TJYXZDXK-009A)。

摘　　要：目的构建脂肪酸分解代谢(FAC)相关基因风险评分预后模型并验证模型中基因ABHD1和PLA2G15在结直肠癌中的作用。方法FAC相关基因集来自GSEA官网。从TCGA下载结直肠癌RNA测序数据和临床信息,并对癌组织和正常组织样本进行FAC相关基因差异分析。单因素Cox回归分析筛选出与预后相关的差异基因,之后,利用LASSO回归进一步分析并筛选出目标基因建立预后模型。外部数据集(GSE39582)验证预后模型。最后采用CCK-8、集落形成和细胞周期实验验证目标基因中ABHD1和PLA2G15在结直肠癌细胞系中的作用。结果102个FAC相关基因通过差异分析、单因素Cox回归分析及LASSO回归分析,筛选出由ABHD1、ACOX1、CPT2、HADH和PLA2G15构建的风险评分预后模型。与低风险评分相比,高风险评分的预后更差。多因素Cox回归分析显示预后模型为独立的预后因素。外部数据集(GSE39582)也验证了该模型评估预后的作用。对ABHD1和PLA2G15基因进行了实验验证,结果表明ABHD1和PLA2G15在体外具有促进结直肠癌细胞增殖的作用。结论FAC相关基因风险模型具有预测结直肠癌患者预后的作用。ABHD1和PLA2G15可能对结直肠癌的生长具有一定促进作用,值得进一步研究。ObjectiveTo construct a prognostic model for fatty acid catabolism (FAC) related genes and validate the role of ABHD1 and PLA2G15 in colorectal cancer.MethodsThe FAC related gene set was obtained from GSEA. RNA sequencing data and clinical information of colorectal cancer were downloaded from TCGA. We performed differential expressed analysis for FAC related genes between tumor and normal samples. Univariate Cox regression analysis was used to screen differential expressed genes associated with prognosis, and then LASSO regression was utilized to further analyze and screen target genes to establish a prognostic model. The prognostic model was validated by an external dataset (GSE39582). Finally, the biological functions of ABHD1 and PLA2G15 in colorectal cancer cell lines were validated using CCK-8, colony formation, and cell cycle assays.ResultsThrough previous analyses, 5 genes (ABHD1, ACOX1, CPT2, HADH, and PLA2G15) among 102 FAC related genes were selected to construct a risk scoring prognostic model. Patients with high-risk scores had a worse prognosis compared to those with low-risk scores. Multivariate Cox regression analysis showed that the prognostic model was an independent prognostic factor. The external dataset (GSE39582) also validated the effect of this prognostic model evaluating prognosis. We conducted experimental validation for these two genes. The experimental results indicated that ABHD1 and PLA2G15 had impacts on promoting the proliferation of colorectal cancer cells in vitro.ConclusionThe FAC prognostic model has a predictive effect on the prognosis of colorectal cancer patients. ABHD1 and PLA2G15 may have a certain promoting effect on the growth of colorectal cancer, which deserves further research.

关 键 词：结直肠肿瘤 脂肪酸分解代谢 ABHD1 PLA2G15 预后 

分 类 号：R735.34[医药卫生—肿瘤]