| 引用本文: | 卢晓丹,洪叶,石嘉丽,郑世雄,莫韵莹,邓俊锋,黄仕涵,冼晓宇,孙思雨,刘天扬,何志妮.砷诱导人角质形成细胞癌变的关键[]基因筛查及预后分析[J].生物信息学,2026,24(3):290-300. |
| Lu Xiaodan,Hong Ye,Shi Jiali,Zheng Shixiong,Mo Yunying,Deng Junfeng,Huang Shihan,Xian Xiaoyu,Sun Siyu,Liu Tianyang,He Zhini.Screening of key genes for arsenic-induced carcinogenesis in human keratinocytes[J].Chinese Journal of Bioinformatics,2026,24(3):290-300. |
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| 砷诱导人角质形成细胞癌变的关键[]基因筛查及预后分析 |
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卢晓丹1,2,洪叶1,2,石嘉丽1,郑世雄1,2,莫韵莹1,2,邓俊锋1,2,黄仕涵1,2,冼晓宇1,2,孙思雨1,刘天扬1,何志妮1,2
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(1.南方医科大学 公共卫生学院,广州 510515;2.国家药品监督管理局化妆品安全评价重点实验室,广州 510515)
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| 摘要: |
| 为了探究砷暴露致HaCaT细胞(人永生化角质形成细胞)差异表达关键基因在皮肤肿瘤中的预后效应,及砷致皮肤癌的潜在分子机制,采用生物信息学方法,从GEO(Gene Expression Omnibus)数据库中下载砷暴露后人角质形成细胞mRNA差异表达芯片数据集(GSE97303),并运用GEO2R在线工具筛选差异表达基因。随后进行GO和KEGG的富集分析,使用STRING工具构建蛋白互作网络(PPI),借助Cytoscape软件的CytoHubba插件识别出与砷暴露致HaCaT细胞中表达变化最显著前10个关键基因。在GEP1A2与皮肤黑色素瘤(Skin Cutaneous Melanoma, SKCM)进行Kaplan-Meier生存预后分析,研究相关基因的预后关联性。最终筛选出上调表达基因289个,差异基因功能主要富集在内质网中的蛋白质加工通路,变化最显著的10个核心基因分别为HSPA5、DNAJB9、HERPUD1、HSP90B1、DNAJC3、PDIA4、HYOU1、XBP1、ATF6、PDIA6。GEPIA2分析显示DNAJB9、HERPUD1、XBP1 的低表达状态与SKCM患者不良预后显著相关(P<0.05),其中 XBP1的调控作用最为突出(P<0.01)。因此,内质网中的蛋白质加工可能在砷暴露致皮肤癌的过程中起到关键作用,XBP1可能通过内质网应激通路参与砷暴露的致癌机制。 |
| 关键词: 生物信息学 砷暴露 皮肤黑色素瘤 XBP1基因 |
| DOI：10.12113/202411007 |
| 分类号:Q343.1 |
| 文献标识码:A |
| 基金项目:东莞市社会发展科技重点项目(No.20231800939892)；广东省药品监督管理局科技项目引导扶持专项(No.2022YDZ11). |
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| Screening of key genes for arsenic-induced carcinogenesis in human keratinocytes |
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Lu Xiaodan1,2, Hong Ye1,2, Shi Jiali1, Zheng Shixiong1,2, Mo Yunying1,2, Deng Junfeng1,2, Huang Shihan1,2, Xian Xiaoyu1,2, Sun Siyu1, Liu Tianyang1, He Zhini1,2
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(1.School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China;2.NMPA Key Laborntory for Safety Evaluation of Cosmetics, Guangzhou, Guangdong 510515, China)
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| Abstract: |
| To investigate the prognostic value of differentially expressed genes in arsenic-exposed HaCaT cells (human immortalized keratinocytes) and the molecular mechanisms of arsenic-induced skin carcinogenesis, we analyzed the mRNA dataset GSE97303 from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using GEO2R. GO and KEGG enrichment analyses were performed to assess DEG functions. A protein-protein interaction (PPI) network was constructed using STRING, and the top 10 hub genes were identified with CytoHubba in Cytoscape. Kaplan-Meier survival analysis via GEPIA2 evaluated the association between hub genes and prognosis in skin cutaneous melanoma (SKCM). We identified 289 upregulated genes, mainly enriched in endoplasmic reticulum (ER) protein processing pathways. The top hub genes were HSPA5, DNAJB9, HERPUD1, HSP90B1, DNAJC3, PDIA4, HYOU1, XBP1, ATF6, and PDIA6. Low expression of DNAJB9, HERPUD1, and XBP1correlated with poorer overall survival in SKCM patients (P<0.05), with XBP1showing the strongest prognostic significance (P<0.01). These results suggest that protein processing in the endoplasmic reticulum may play a critical role in the development of skin cancer associated with arsenic exposure. XBP1is likely involved in the carcinogenic mechanism induced by arsenic exposure through the endoplasmic reticulum stress pathway. |
| Key words: Bioinformatics Arsenic exposure SKCM XBP1 |
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