基于生物信息学分析跨膜蛋白132A在肝癌中的表达及其临床意义

肝癌电子杂志 ›› 2024, Vol. 11 ›› Issue (3): 33-41.

基于生物信息学分析跨膜蛋白132A在肝癌中的表达及其临床意义

赵航祺¹, 马小雯², 张天爱³, 李柏峰^1,*

1.中国医科大学附属第一医院浑南院区普通外科肝胆胰外科, 沈阳 110001;
2.中国医科大学第一临床学院106期, 沈阳 110122;
3.北部战区总医院重症医学科, 沈阳 110003

收稿日期:2024-02-22 出版日期:2024-09-30 发布日期:2024-11-21
通讯作者: ^*李柏峰,E-mail：libaifeng818@126.com
基金资助:
辽宁省教育厅科学研究经费项目（JCZR2020006）

Expression and clinical significance of transmembrane protein 132A in liver cancer based on bioinformatics

Zhao Hangqi¹, Ma Xiaowen², Zhang Tian'ai³, Li Baifeng^1,*

1. Department of Hepatobiliary and Pancreatic Surgery, Hunnan Branch of First Affiliated Hospital of China Medical University, Shenyang 110122, China;
2. 106K, First Clinical College, China Medical University, Shenyang 110122, China;
3. Intensive Care Unit, General Hospital of Northern Theater Command, Shenyang 110122, China

Received:2024-02-22 Online:2024-09-30 Published:2024-11-21
Contact: ^*Li Baifeng, E-mail: libaifeng818@126.com

摘要/Abstract

摘要： 目的：基于公共数据库探究跨膜蛋白132A（TMEM132A）在肝癌中的表达模式及临床意义。
方法：利用肿瘤基因组图谱并基于基因表达数据库优选其中的GSE14520、GSE60502数据集分析TMEM132A在肝癌与癌旁组织中的mRNA表达水平,及与临床因素的相关性。通过HPA数据库获取TMEM132A在组织中的免疫组织化学结果。利用Kaplan-Meier法探讨TMEM132A与患者预后的相关性。运用受试者操作特征曲线探究TMEM132A是否可以作为诊断指标。通过癌症药物敏感基因组学预测TMEM132A对化疗药物的药物敏感性。通过单样本GSEA、TIMER、STORMAL SCORE和免疫检查点热图,对TEME132A进行免疫分析。linkedomics网站用于对TMEM132A差异基因进行基因集富集分析。利用STRING数据库预测TMEM132A的互作蛋白。
结果：TMEM132A在肝癌组织表达显著高于癌旁组织（P<0.05）,定位于胞浆、胞膜。TMEM132A高表达与肿瘤分期、分级、甲胎蛋白水平和体重显著正相关。TMEM132A高表达提示患者预后不良,可作为准确的诊断指标。TMEM132A对多种化疗药物敏感,且被多种免疫细胞浸润,可以作为药物治疗及免疫治疗的研究靶点。癌组织中TMEM132的启动子甲基化水平显著降低。TMEM132A影响细胞黏附,脂肪酸代谢等信号通路。
结论：TMEM132A在肝癌中高表达,与患者预后不良正相关。

关键词: 肝癌, 跨膜蛋白132A, 肿瘤基因组图谱

Abstract: Objective: To explore the expression pattern and clinical significance of transmembrane protein 132A (TMEM132A) in liver cancer based on public databases.
Methods: The Cancer Genome Atlas and GSE14520, GSE60502 of Gene Expression Omnibus was used to analyze the mRNA level of TMEM132A in liver cancer and adjacent tissues, the promoter methylation level, and the correlation with clinical factors. The immunohistochemical results of TMEM132A in tissues were obtained through HPA database. Kaplan-Meier method was used to explore the correlation between TMEM132A and the prognosis of patients. Receiver operating characteristic curve was used to explore whether TMEM132A could accurately diagnose patients. The drug sensitivity of TMEM132A to chemotherapy drugs was predicted by cancer drug sensitivity genomics. Immune analysis of TEME132A was performed by single-sample GSEA, TIMER, STORMAL SCORE and immune checkpoint heatmap. Linkedomics website was used to perform gene set enrichment analysis for differential genes of TMEM132A. The STRING database was used to predict the interacting proteins of TMEM132A.
Results: The expression of MEM132A in HCC tissues was significantly higher than that in adjacent tissues (P<0.05), and it was located in the cytoplasm and cell membrane. The high expression of TMEM132A was positively correlated with tumor stage, grade, AFP level and body weight. High expression of TMEM132A indicates poor prognosis and can be used as an accurate diagnostic indicator. TMEM132A is sensitive to a variety of chemotherapy drugs and infiltrated by a variety of immune cells, which can be used as a research target for drug therapy and immunotherapy. The promoter methylation level of TMEM132 was significantly decreased in cancer tissues. TMEM132A affects cell adhesion, fatty acid metabolism and other signaling pathways.
Conclusion: TMEM132A is highly expressed in HCC and positively correlated with poor prognosis.

Key words: Liver cancer, Transmembrane protein 132A, The cancer genome atlas

赵航祺, 马小雯, 张天爱, 李柏峰. 基于生物信息学分析跨膜蛋白132A在肝癌中的表达及其临床意义[J]. 肝癌电子杂志, 2024, 11(3): 33-41.

Zhao Hangqi, Ma Xiaowen, Zhang Tian'ai, Li Baifeng. Expression and clinical significance of transmembrane protein 132A in liver cancer based on bioinformatics[J]. Electronic Journal of Liver Tumor, 2024, 11(3): 33-41.

参考文献

[1] 中华人民共和国国家卫生健康委员会医政司.原发性肝癌诊疗指南(2022年版)[J/CD].肝癌电子杂志,2022,9(1):1-22.
[2] WEI W, JIAN P E, LI S H, et al.Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety[J]. Cancer Commun (Lond), 2018, 38(1): 61.
[3] OH-HASHI K, IMAI K, KOGA H, et al.Knockdown of transmembrane protein 132A by RNA interference facilitates serum starvation-induced cell death in Neuro2a cells[J]. Mol Cell Biochem, 2010, 342(1-2): 117-123.
[4] GAO Q, CHEN Y, YUE L, et al.Knockdown of TMEM132A restrains the malignant phenotype of gastric cancer cells via inhibiting Wnt signaling[J]. Nucleosides Nucleotides Nucleic Acids, 2023, 42(5): 343-357.
[5] WU R, LI D, FENG D, et al.Transmembrane protein 132A (TMEM132A) predicts overall survival for bladder cancer patients[J]. Asian J Surg, 2023, 46(9): 3804-3806.
[6] ZHOU T, CAI Z, MA N, et al.A novel ten-gene signature predicting prognosis in hepatocellular carcinoma[J]. Front Cell Dev Biol, 2020, 8: 629.
[7] ZHOU T, CAI Z, MA N, et al.A novel ten-gene signature predicting prognosis in hepatocellular carcinoma[J]. Front Cell Dev Biol, 2020, 8: 629.
[8] CHANDRASHEKAR D S, BASHEL B, BALASUBRAMANYA S, et al.UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses[J]. Neoplasia, 2017, 19(8): 649-658.
[9] CHANDRASHEKAR D S, KARTHIKEYAN S K, KORLA P K, et al.UALCAN: an update to the integrated cancer data analysis platform[J]. Neoplasia, 2022, 25: 18-27.
[10] MA X, FAN M, YANG K, et al.ZNF500 abolishes breast cancer proliferation and sensitizes chemotherapy by stabilizing P53 via competing with MDM2[J]. Cancer Sci, 2023, 114(11): 4237-4251.
[11] JIN K, QIU S, JIN D, et al.Development of prognostic signature based on immune-related genes in muscle-invasive bladder cancer: bioinformatics analysis of TCGA database[J]. Aging (Albany NY), 2021, 13(2): 1859-1871.
[12] WANG J, SUN J, LIU L N, et al.Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy[J]. Nat Med, 2019, 25(4): 656-666.
[13] LI T, FU J, ZENG Z, et al.TIMER2.0 for analysis of tumor-infiltrating immune cells[J]. Nucleic Acids Res, 2020, 48(W1): W509-W514.
[14] JIANG Q, SUN J, CHEN H, et al.Establishment of an immune cell infiltration score to help predict the prognosis and chemotherapy responsiveness of gastric cancer patients[J]. Front Oncol, 2021, 11: 650673.
[15] GREGERSEN N O, BUTTENSCHON H N, HEDEMAND A, et al.Are TMEM genes potential candidate genes for panic disorder?[J]. Psychiatr Genet, 2014, 24(1): 37-41.
[16] OH-HASHI K, NARUSE Y, AMAYA F, et al.Cloning and characterization of a novel GRP78-binding protein in the rat brain[J]. J Biol Chem, 2003, 278(12): 10531-10537.
[17] OH-HASHI K, HIRATA Y, KOGA H, et al.GRP78-binding protein regulates cAMP-induced glial fibrillary acidic protein expression in rat C6 glioblastoma cells[J]. FEBS Lett, 2006, 580(16): 3943-3947.
[18] ZHANG Y, ZHANG Z.The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications[J]. Cell Mol Immunol, 2020, 17(8): 807-821.
[19] RAMIREZ C, TARANTO D, ANDO-KURI M, et al.Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma[J]. Nat Commun, 2024, 15(1): 2581.
[20] CURRIE E, SCHULZE A, ZECHNER R, et al.Cellular fatty acid metabolism and cancer[J]. Cell Metab, 2013, 18(2): 153-161.
[21] LI Y, LI M, JIN F, et al.DNAJC12 promotes lung cancer growth by regulating the activation of beta-catenin[J]. Int J Mol Med, 2021, 47(6): 105.
[22] HUNG MC, YANG R, SUN Y.Powering tumor metastasis with recycled fuel[J]. Cancer Cell, 2016, 30(3): 374-375.