背景:尽管现代医学技术突飞猛进,肾透明细胞癌(KIRC)仍然是泌尿外科具有挑战性的临床问题。由于其高杀伤力,研究人员迫切需要寻找有用的标志物来突破治疗难题。因此,本研究探讨了ADH5对KIRC的总体生存期(OS)和免疫学的价值。
方法:使用外部数据库和qRT-PCR验证TCGA数据库中ADH5的基因表达矩阵和临床信息。为了证实ADH5与KIRC预后之间的相关性,采用单因素/多因素Cox回归分析.我们还探索了KIRC中与ADH5相关的信号通路,并研究了其与免疫的关系。
结果:mRNA和蛋白质水平显示KIRC中ADH5的明显下调。相关分析显示ADH5与组织学分级直接相关,临床分期,和TMN阶段(p<0.05)。单因素和多因素Cox回归分析确定ADH5是影响KIRC预后的独立因素。富集分析研究了5条与ADH5相关的信号通路。结果显示ADH5和TMB之间没有相关性,TNB,和MSI。从免疫学的角度来看,发现ADH5与肿瘤微环境有关,免疫细胞浸润,和免疫检查点。较低的ADH5表达与更高的免疫疗法反应性相关。单细胞测序显示ADH5在免疫细胞中高表达。
结论:ADH5可能是一个有前景的预后生物标志物和KIRC的潜在治疗靶点。此外,发现ADH5低表达的KIRC患者对免疫治疗更敏感。
BACKGROUND: Despite the rapid advances in modern medical technology, kidney renal clear cell carcinoma (KIRC) remains a challenging clinical problem in urology. Researchers urgently search for useful markers to break through the therapeutic conundrum due to its high lethality. Therefore, the study explores the value of
ADH5 on overall survival (OS) and the immunology of KIRC.
METHODS: The gene expression matrix and clinical information on ADH5 in the TCGA database were validated using external databases and qRT-PCR. To confirm the correlation between ADH5 and KIRC prognosis, univariate/multivariate Cox regression analysis was used. We also explored the signaling pathways associated with ADH5 in KIRC and investigated its association with immunity.
RESULTS: The mRNA and protein levels showed an apparent downregulation of ADH5 in KIRC. Correlation analysis revealed that ADH5 was directly related to histological grade, clinical stage, and TMN stage (p < 0.05). Univariate and multivariate Cox regression analysis identified ADH5 as an independent factor affecting the prognosis of KIRC. Enrichment analysis looked into five
ADH5-related signaling pathways. The results showed no correlation between
ADH5 and TMB, TNB, and MSI. From an immunological perspective, ADH5 was found to be associated with the tumor microenvironment, immune cell infiltration, and immune checkpoints. Lower
ADH5 expression was associated with greater responsiveness to immunotherapy. Single-cell sequencing revealed that
ADH5 is highly expressed in immune cells.
CONCLUSIONS: ADH5 could be a promising prognostic biomarker and a potential therapeutic target for KIRC. Besides, it was found that KIRC patients with low ADH5 expression were more sensitive to immunotherapy.