Abnormally upregulated CNIH4 and TOMM40L genes may be associated with prognosis of hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

JIANG Min ,  ZHAO Yujun

The Second Department of General Surgery, Guangdong Second Provincial General Hospital, Guangzhou 510317, P. R. China;

Corresponding author：

ZHAO Yujun, Email: yujunzhao020@126.com

Keywords：

hepatocellular carcinoma; CNIH4; TOMM40L; bioinformatics analysis; prognosis

DOI：

10.7507/1007-9424.202109022

Video：

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Objective To explore the aberrantly expressed genes in hepatocellular carcinoma (HCC) and their relationship with prognosis of HCC through bioinformatics analysis. Methods Five datasets related to HCC were selected from the GeneExpression Omnibus database to explore differentially expressed genes (DEGs), followed by further gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The co-upregulated genes CNIH4 and TOMM40 were selected to explore the differences in their expressions in HCC tissues and normal tissues, and to explore the relationship between their expressions and the 5-year survival of patients by using TCGA database. Tissues and paraneoplastic tissues of eight cases of HCC who underwent surgery at the Guangdong Second Provincial General Hospital were collected to verify the expression differences of CNIH4 and TOMM40L mRNA. Results A total of 25 up-regulated genes and 21 down-regulated genes were identified in this study. The results of GO analysis and KEGG analysis indicated that DEGs were mainly related to catabolism, cell division, DNA replication and repair. The results of TCGA database analysis showed that the expression of up-regulated genes CNIH4 mRNA and TOMM40L mRNA were up-regulated in HCC tissues as compared with normal tissues (P<0.05) and that the 5-year survival of patients in the high expression group was worse than that in the low expression group (P<0.05). The results of clinical samples showed that CNIH4 mRNA and TOMM40L mRNA were up-regulated in HCC tissues as compared with paraneoplastic tissues. Conclusion CNIH4 and TOMM40L genes are up-regulated in HCC tissues, and their high expressions are associated with poor prognosis, and may be potential biomarkers and prognostic indicators for HCC.

Citation： JIANG Min, ZHAO Yujun. Abnormally upregulated CNIH4 and TOMM40L genes may be associated with prognosis of hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(7): 904-909. doi: 10.7507/1007-9424.202109022 Copy

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22.	Yang W, Shin HY, Cho H, et al. TOM40 inhibits ovarian cancer cell growth by modulating mitochondrial function including intracellular ATP and ROS levels. Cancers (Basel), 2020, 12(5): 1329. doi: 10.3390/cancers12051329.
23.	Cardoso R, Lemos C, Oliveiros B, et al. APOEɛ4-TOMM40L haplotype increases the risk of mild cognitive impairment conversion to Alzheimer’s disease. J Alzheimers Dis, 2020, 78(2): 587-601.
24.	Wang WJ, Wang Y, Chen HZ, et al. Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway. Nat Chem Biol, 2014, 10(2): 133-140.
25.	Zhou M, Ye Z, Gu Y, et al. Genomic analysis of drug resistant pancreatic cancer cell line by combining long non-coding RNA and mRNA expression profling. Int J Clin Exp Pathol, 2015, 8(1): 38-52.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. 周家琛, 郑荣寿, 王少明, 等. 2020年中国和世界部分国家主要消化道肿瘤负担比较. 肿瘤综合治疗电子杂志, 2021, 7(2): 26-32.
3. 崔富强, 庄辉. 中国乙型肝炎的流行及控制进展. 中国病毒病杂志, 2018, 8(4): 257-264.
4. 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范 (2019年版). 中国实用外科杂志, 2020, 40(2): 121-138.
5. 刘允怡, 樊嘉, 方驰华, 等. 原发性肝癌三维可视化技术操作及诊疗规范 (2020版). 中国实用外科杂志, 2020, 40(9): 991-1011.
6. 中国医师协会介入医师分会临床诊疗指南专委会. 中国肝细胞癌经动脉化疗栓塞 (TACE) 治疗临床实践指南 (2021年版). 中华医学杂志, 2021, 101(24): 1848-1862.
7. 何玲华, 刘凯敏, 佟虹兴, 等. 肝细胞肝癌免疫检查点阻断治疗疗效相关生物标志物的研究进展. 中国普外基础与临床杂志, 2022, 29(1): 112-117.
8. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 2008, 359(4): 378-390.
9. Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increasedα-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol, 2019, 20(2): 282-296.
10. Uhlen M, Zhang C, Lee S, et al. A pathology atlas of the human cancer transcriptome. Science, 2017, 357(6352): eaan2507. doi: 10.1126/science.aan2507.
11. Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res, 2003, 13(11): 2498-2504.
12. Tang Z, Kang B, Li C, et al. GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res, 2019, 47(W1): W556-W560.
13. Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell, 2017, 169(7): 1327-1341.e23.
14. Zhang Q, He Y, Luo N, et al. Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell, 2019, 179(4): 829-845.e20.
15. Zheng C, Zheng L, Yoo JK, et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell, 2017, 169(7): 1342-1356.e16.
16. 王何斌, 刘德钦, 杨茂辉, 等. 应用生物信息学分析筛选肝细胞癌关键基因及表达验证. 中国普外基础与临床杂志, 2021, 28(6): 743-750.
17. Yeo W, Chung HC, Chan SL, et al. Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: a multicenter phase Ⅰ/Ⅱ study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase Ⅱ Consortium and the Cancer Therapeutics Research Group. J Clin Oncol, 2012, 30(27): 3361-3367.
18. Shanks NF, Savas JN, Maruo T, et al. Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L. Cell Rep, 2012, 1(6): 590-598.
19. Shanks NF, Cais O, Maruo T, et al. Molecular dissection of the interaction between the AMPA receptor and cornichon homolog-3. J Neurosci, 2014, 34(36): 12104-12120.
20. Sauvageau E, Rochdi MD, Oueslati M, et al. CNIH4 interacts with newly synthesized GPCR and controls their export from the endoplasmic reticulum. Traffic, 2014, 15(4): 383-400.
21. Mishra S, Bernal C, Silvano M, et al. The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases. Oncogene, 2019, 38(29): 5817-5837.
22. Yang W, Shin HY, Cho H, et al. TOM40 inhibits ovarian cancer cell growth by modulating mitochondrial function including intracellular ATP and ROS levels. Cancers (Basel), 2020, 12(5): 1329. doi: 10.3390/cancers12051329.
23. Cardoso R, Lemos C, Oliveiros B, et al. APOEɛ4-TOMM40L haplotype increases the risk of mild cognitive impairment conversion to Alzheimer’s disease. J Alzheimers Dis, 2020, 78(2): 587-601.
24. Wang WJ, Wang Y, Chen HZ, et al. Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway. Nat Chem Biol, 2014, 10(2): 133-140.
25. Zhou M, Ye Z, Gu Y, et al. Genomic analysis of drug resistant pancreatic cancer cell line by combining long non-coding RNA and mRNA expression profling. Int J Clin Exp Pathol, 2015, 8(1): 38-52.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Abnormally upregulated CNIH4 and TOMM40L genes may be associated with prognosis of hepatocellular carcinoma

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