The expression of GSDM gene family in primary liver cancer and its influence on prognosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

GUO Ying ¹ ,  GUO Qiuying ²

1. Department of Hepatology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China;
2. The Second Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P. R. China;

Corresponding author：

GUO Qiuying, Email: 516512664@qq.com

Keywords：

Primary liver cancer; gasdermin gene; data analysis; prognosis

DOI：

10.7507/1007-9424.202105003

Video：

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Objective To investigate the expression of gasdermin (GSDM) gene family in primary liver cancer and its clinical significance. Methods The Gene Expression Profile Data Dynamic Analysis (GEPIA2) database was used to analyze the expression levels of GSDM gene family in primary liver cancer and normal tissues, and survival analysis was performed to explore its relationship with prognosis; GEPIA2 database was used to explore the relationship between GSDM gene family and TNM staging of patients with primary liver cancer. We used GeneMANIA database to predict genes that may interact with GSDM gene family, and used Metascape website for functional enrichment analysis. Finally, we used TIMER database to explore the relationship of expression of GSDM gene family and immune cell infiltration in the tumor microenvironment of primary liver cancer. Results Compared with normal liver tissues, GSDMA, GSDMC, GSDMD, and GSDME were highly expressed in primary liver cancer (P<0.050), and GSDMB and DFNB59 were low expressed (P<0.050); results of univariate Cox proportional hazard regression model showed that the differential expressions of GSDMD, GSDME, and DFNB59 were related to the overall survival of patients (P<0.050), and the results of the multivariate Cox proportional hazard regression model showed that GSDME could be used as an independent predictor of the prognosis of liver cancer patients (P<0.050). With the increase of TNM staging in patients with liver cancer, the expressions of GSDMA and GSDMC also gradually increased (P<0.050). Further enrichment analysis showed that the GSDM gene family was involved in pyrolysis and various immune-related biological processes. Conclusion The GSDM gene is differentially expressed in primary liver cancer, participates in immune-related biological processes, and its expression is related to clinicopathological staging and patients’ prognosis.

Citation： GUO Ying, GUO Qiuying. The expression of GSDM gene family in primary liver cancer and its influence on prognosis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(3): 328-336. doi: 10.7507/1007-9424.202105003 Copy

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21.	Shen HH, Yang YX, Meng X, et al. NLRP3: a promising therapeutic target for autoimmune diseases. Autoimmun Rev, 2018, 17(7): 694-702.
22.	Jia C, Chen H, Zhang J, et al. Role of pyroptosis in cardiovascular diseases. Int Immunopharmacol, 2019, 67: 311-318.
23.	Pezuk JA. Pyroptosis in combinatorial treatment to improve cancer patients’ outcome, is that what we want? EBioMedicine, 2019, 41: 17-18.
24.	Liu X, Zhang Z, Ruan J, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature, 2016, 535(7610): 153-158.
25.	Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature, 2016, 535(7610): 111-116.
26.	Kuang S, Zheng J, Yang H, et al. Structure insight of GSDMD reveals the basis of GSDMD autoinhibition in cell pyroptosis. Proc Natl Acad Sci U S A, 2017, 114(40): 10642-10647.
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28.	Chen X, He WT, Hu L, et al. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell Res, 2016, 26(9): 1007-1020.
29.	黄康, 彭贵主. 基于生物信息学分析肝细胞癌的核心基因. 中国普外基础与临床杂志, 2020, 27(11): 1357-1364.
30.	Thorsson V, Gibbs DL, Brown SD, et al. The immune landscape of cancer. Immunity, 2018, 48(4): 812-830. e14. doi: 10.1016/j.immuni.2018.03.023.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Villanueva A. Hepatocellular carcinoma. N Engl J Med, 2019, 380(15): 1450-1462.
3. Mu D, Qin F, Li B, et al. Identification of the sixth complement component as potential key genes in hepatocellular carcinoma via eioinformatics analysis. Biomed Res Int, 2020, 2020: 7042124.
4. Liu X, Xia S, Zhang Z, et al. Channelling inflammation: gasdermins in physiology and disease. Nat Rev Drug Discov, 2021, 20(5): 384-405.
5. Xia X, Wang X, Cheng Z, et al. The role of pyroptosis in cancer: pro-cancer or pro-“host”? Cell Death Dis, 2019, 10(9): 650. doi: 10.1038/s41419-019-1883-8.
6. Xu YJ, Zheng L, Hu YW, et al. Pyroptosis and its relationship to atherosclerosis. Clin Chim Acta, 2018, 476: 28-37.
7. Wu J, Lin S, Wan B, et al. Pyroptosis in liver disease: new insights into disease mechanisms. Aging Dis, 2019, 10(5): 1094-1108.
8. Pirzada RH, Javaid N, Choi S. The roles of the NLRP3 inflammasome in neurodegenerative and metabolic diseases and in relevant advanced therapeutic interventions. Genes (Basel), 2020, 11(2): 131. doi: 10.3390/genes11020131.
9. Zhou CB, Fang JY. The role of pyroptosis in gastrointestinal cancer and immune responses to intestinal microbial infection. Biochim Biophys Acta Rev Cancer, 2019, 1872(1): 1-10.
10. Wang M, Jiang S, Zhang Y, et al. The multifaceted roles of pyroptotic cell death pathways in cancer. Cancers (Basel), 2019, 11(9): 1313. doi: 10.3390/cancers11091313.
11. Zhang Y, Yang H, Sun M, et al. Alpinumisoflavone suppresses hepatocellular carcinoma cell growth and metastasis via NLRP3 inflammasome-mediated pyroptosis. Pharmacol Rep, 2020, 72(5): 1370-1382.
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. Nagy Á, Munkácsy G, Győrffy B. Pancancer survival analysis of cancer hallmark genes. Sci Rep, 2021, 11(1): 6047. doi: 10.1038/s41598-021-84787-5.
14. Franz M, Rodriguez H, Lopes C, et al. GeneMANIA update 2018. Nucleic Acids Res, 2018, 46(W1): W60-W64.
15. Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun, 2019, 10(1): 1523. doi: 10.1038/s41467-019-09234-6.
16. Li T, Fan J, Wang B, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res, 2017, 77(21): e108-e110. doi: 10.1158/0008-5472.CAN-17-0307.
17. Ru B, Wong CN, Tong Y, et al. TISIDB: an integrated repository portal for tumor-immune system interactions. Bioinformatics, 2019, 35(20): 4200-4202.
18. Gao YX, Yang TW, Yin JM, et al. Progress and prospects of biomarkers in primary liver cancer (review). Int J Oncol, 2020, 57(1): 54-66.
19. Zhang G, Kang Z, Mei H, et al. Promising diagnostic and prognostic value of six genes in human hepatocellular carcinoma. Am J Transl Res, 2020, 12(4): 1239-1254.
20. Song L, Pei L, Yao S, et al. NLRP3 inflammasome in neurological diseases, from functions to therapies. Front Cell Neurosci, 2017, 11: 63. doi: 10.3389/fncel.2017.00063.
21. Shen HH, Yang YX, Meng X, et al. NLRP3: a promising therapeutic target for autoimmune diseases. Autoimmun Rev, 2018, 17(7): 694-702.
22. Jia C, Chen H, Zhang J, et al. Role of pyroptosis in cardiovascular diseases. Int Immunopharmacol, 2019, 67: 311-318.
23. Pezuk JA. Pyroptosis in combinatorial treatment to improve cancer patients’ outcome, is that what we want? EBioMedicine, 2019, 41: 17-18.
24. Liu X, Zhang Z, Ruan J, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature, 2016, 535(7610): 153-158.
25. Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature, 2016, 535(7610): 111-116.
26. Kuang S, Zheng J, Yang H, et al. Structure insight of GSDMD reveals the basis of GSDMD autoinhibition in cell pyroptosis. Proc Natl Acad Sci U S A, 2017, 114(40): 10642-10647.
27. Aglietti RA, Dueber EC. Recent insights into the molecular mechanisms underlying pyroptosis and gasdermin family functions. Trends Immunol, 2017, 38(4): 261-271.
28. Chen X, He WT, Hu L, et al. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell Res, 2016, 26(9): 1007-1020.
29. 黄康, 彭贵主. 基于生物信息学分析肝细胞癌的核心基因. 中国普外基础与临床杂志, 2020, 27(11): 1357-1364.
30. Thorsson V, Gibbs DL, Brown SD, et al. The immune landscape of cancer. Immunity, 2018, 48(4): 812-830. e14. doi: 10.1016/j.immuni.2018.03.023.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The expression of GSDM gene family in primary liver cancer and its influence on prognosis

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