基于生物信息學分析CISD2在肝細胞癌中的表達意義及功能網絡關系

劉發煇 侯婉云 朱麗蘭 羅春英

【摘要】目的探究CDGSH鐵硫結構域2（CISD2）在肝細胞癌（HCC）發生發展中的作用、臨床病理意義及其潛在作用機制。

方法Kaplan Meierplotter分析CISD2 mRNA表達與HCC患者5年生存率的關系;在線網頁工具STRING構建CISD2蛋白相互作用網絡，基因本體論富集分析CISD2蛋白質功能;網頁工具TIMER分析CISD2在HCC中與免疫細胞浸潤含量之間的關系;GSEA分析CISD2高表達在HCC中參與的信號通路。

結果（1）CISD2 mRNA高表達的HCC患者的5年總生存率低于低表達患者;（2）CISD2與B細胞、CD4+T細胞、CD8+T細胞、巨噬細胞和樹突狀細胞的浸潤呈負相關;（3）CISD2主要參與了細胞內二價鐵硫簇結合，鐵硫簇綁定以及金屬集群綁定;（4）GSEA分析表明CISD2高表達在HCC中促進卟啉和葉綠素代謝，戊糖、葡萄糖醛酸轉換，抗壞血酸和醛酸代謝，氨基糖和核苷酸糖代謝，淀粉和蔗糖代謝等多條代謝通路。

結論（1）在HCC中，CISD2 mRNA高表達與HCC患者的較差預后有關。（2）CISD2可能通過影響腫瘤細胞的鐵離子、能量代謝和腫瘤免疫微環境促進腫瘤細胞的生存和增殖。

【關鍵詞】CISD2 ;肝細胞癌;生物信息學;預后;功能網絡分析

中圖分類號：R735.7文獻標志碼：ADOI：10.3969/j.issn.10031383.2020.06.003

【Abstract】ObjectiveTo investigate the role，clinicopathological significance and potential mechanism of CDGSH Iron Sulfur Domain 2（CISD2） in the occurrence and development of hepatocellular carcinoma（HCC）.

MethodsKaplanMeierplotter was used to analyze relationship between CISD2 mRNA expression and 5year survival rate of HCC patients.Online web tool STRING was used to build CISD2 protein interaction network，gene ontology enrichment was used to analyze CISD2 protein function.In addition，Web TIMER was used? to analyze relationship between CISD2 and the infiltration of immune cells in HCC，and GSEA was used to analyze the signaling pathways involved in the high expression of CISD2 in HCC.

Results（1） 5year overall survival rate of HCC patients with high CISD2 mRNA expression was lower than that of patients with low CISD2 mRNA expression.（2） CISD2 was negatively correlated with the infiltration of B cells，CD4+T cells，CD8+T cells，macrophages，and dendritic cells.（3） CISD2 mainly involved in the bindings of the ironsulfur group，ironsulfur cluster，and metal cluster.（4） GSEA analysis showed that CISD2 high expression promoted porphyrin and chlorophyll metabolism，pentose and glucuronic acid conversion，ascorbic acid and aldehyde acid metabolism，amino and nucleotide glucose metabolism，and starch and sucrose metabolism in HCC.

Conclusion（1） In HCC，high CISD2 mRNA expression is associated with poor prognosis in HCC patients.（2） CISD2 may promote the survival and proliferation of tumor cells by affecting the iron ion，energy metabolism and tumor immune microenvironment of tumor cells.

【Key words】CISD2;HCC;bioinformatics;prognosis;functional network analysis

肝細胞癌（Hepatocellular Carcinoma，HCC）是臨床上最常見的惡性腫瘤之一，在與癌癥相關的死亡原因中，HCC是死亡率第三的腫瘤[1]。但其潛伏期長，多數患者在肝癌晚期才出現癥狀，由于肝癌的高復發率和高轉移率，晚期肝癌患者的5年生存率不超過5%。因此，如何在早期對HCC進行準確判斷和檢測對HCC治療具有積極的意義。在過去的20年中，大量的分子標志物被發現在HCC患者中異常表達，它們都具有潛在的臨床應用價值?！?br>