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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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.
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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. APOE?4-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, 鄭榮壽, 王少明, 等. 2020年中國和世界部分國家主要消化道腫瘤負擔比較. 腫瘤綜合治療電子雜志, 2021, 7(2): 26-32.
3. 崔富強, 莊輝. 中國乙型肝炎的流行及控制進展. 中國病毒病雜志, 2018, 8(4): 257-264.
4. 中華人民共和國國家衛生健康委員會醫政醫管局. 原發性肝癌診療規范 (2019年版). 中國實用外科雜志, 2020, 40(2): 121-138.
5. 劉允怡, 樊嘉, 方馳華, 等. 原發性肝癌三維可視化技術操作及診療規范 (2020版). 中國實用外科雜志, 2020, 40(9): 991-1011.
6. 中國醫師協會介入醫師分會臨床診療指南專委會. 中國肝細胞癌經動脈化療栓塞 (TACE) 治療臨床實踐指南 (2021年版). 中華醫學雜志, 2021, 101(24): 1848-1862.
7. 何玲華, 劉凱敏, 佟虹興, 等. 肝細胞肝癌免疫檢查點阻斷治療療效相關生物標志物的研究進展. 中國普外基礎與臨床雜志, 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, 劉德欽, 楊茂輝, 等. 應用生物信息學分析篩選肝細胞癌關鍵基因及表達驗證. 中國普外基礎與臨床雜志, 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. APOE?4-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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