基于生物信息学探索RPS14作为癌症多功能生物标志物的价值：对诊断、预后及免疫治疗反应的启示

Bioinformatics-based exploration of RPS14 as a multifaceted biomarker in cancer： implications for diagnosis，prognosis，and immunotherapeutic response

摘要

目的 探究核糖体蛋白S14（Ribosomal protein S14，RPS14）在泛癌中的差异表达变化，分析其与各癌症类型的临床特征、生存预后、免疫浸润、药物敏感性以及在癌症中的潜在作用和调控机制。 方法 利用癌症基因组图谱（TCGA）和临床蛋白质组肿瘤分析协作组（CPTAC）数据库分析RPS14在各类癌症中的基因和蛋白质表达水平与患者疾病分期和预后的相关性。从互作基因/蛋白质检索工具数据库（STRING）数据库获取各类癌症中与RPS14相互作用的基因，进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。利用人类转录因子靶基因数据库（HTFtarget）等数据库预测RPS14的转录调控因子。通过肿瘤免疫评估资源数据库2.0（TIMER2.0）评估RPS14的免疫调节作用。借助基因集癌症分析数据库（GSCA）探究RPS14基因表达、癌症治疗反应以及基因组药物敏感性之间的关系。 结果 RPS14在多种癌症中表达失调，特别是在胆管癌、结肠腺癌、多形性胶质母细胞瘤和肝细胞癌中上调，在肾透明细胞癌和前列腺腺癌中下调。RPS14异常表达与肝细胞癌患者较短的总生存期密切相关。这提示RPS14作为这些癌症，尤其是肝细胞癌的诊断和预后标志物的潜力。功能富集分析强调RPS14参与核糖体信号通路并与多种药物治疗敏感性相关。此外，RPS14与多个免疫基因的关联暗示RPS14的调控与CD8⁺ T细胞和其他免疫细胞的肿瘤浸润密切相关。 结论 RPS14在多种癌症的恶性表型、功能机制、生存预后、肿瘤微环境、治疗潜力和药物敏感性预测中发挥重要作用，是一个有前景的、可预测癌症结果的生物标志物和治疗靶点。

Abstract

Objective : To explore the differential expression changes of ribosomal protein S14 （RPS14） in pan-cancer， and to analyze its correlation with the clinical characteristics， survival prognosis， immune infiltration， drug sensitivity of various cancer types， as well as its potential role and regulatory mechanism in cancer. Methods RPS14 mRNA and protein expression levels were analyzed using data from the cancer genome atlas and clinical proteomic tumor analysis consortium. Their associations with tumor stage and patient prognosis were evaluated across cancer types. RPS14 interacting genes were obtained from the search tool for the retrieval of interacting genes/proteins database and subjected to gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses. Potential transcription factors regulating RPS14 were predicted using human transcription factor target database and related databases. The immunomodulatory role of RPS14 was assessed using tumor immune estimation resource，version 2.0. The gene set cancer analysis database was used to examine the relationships among RPS14 expression，therapeutic response and drug sensitivity. Results RPS14 showed dysregulated expression in multiple cancer types， especially upregulated in cholangiocarcinoma，colon adenocarcinoma，glioblastoma multiforme and liver hepatocellular carcinoma， and downregulated in kidney renal clear cell carcinoma and prostate adenocarcinoma. Aberrant RPS14 expression was closely associated with shorter overall survival in patients with LIHC. These findings suggest that RPS14 may serve as a diagnostic and prognostic marker，particularly in liver hepatocellular carcinoma. Functional enrichment analysis showed that RPS14 related genes were mainly involved in ribosome-associated pathways and were linked to sensitivity to several anticancer drugs. In addition，RPS14 was correlated with multiple immune related genes，suggesting a potential association with tumor infiltration of CD8⁺ T cells and other immune cells. Conclusion RPS14 is involved in cancer progression，functional regulation，prognosis，the tumor microenvironment，therapeutic potential， and drug sensitivity prediction. It may serve as a promising biomarker for predicting cancer outcomes and as a potential therapeutic target.

关键词

核糖体蛋白S14 / 泛癌生物信息学分析 / 癌症生物标志物 / 预后 / 免疫浸润

Key words

Ribosomal protein S14 / Pan-cancer bioinformatics analysis / Cancer biomarker / Prognosis / Immune infiltration