清除细胞肾细胞癌（ccRCC）是成人泌尿学中一种常见的癌症，常导致转移和预后不良。最近，在肿瘤免疫学和衰老研究方面的进展为肾癌的治疗开辟了新的可能性。因此，鉴定免疫治疗的潜在靶点和预后生物标志物变得越来越紧迫。利用GSE168845数据，我们通过交叉比对差异表达的免疫相关基因和衰老相关基因，鉴定了免疫-衰老相关差异表达基因（IAR-DEGs）。通过单变量和多变量Cox回归分析确定了IAR-DEGs的预后价值，结果显示KL是ccRCC的一个独立预后因子。我们还研究了KL与各种免疫相关因素的相关性，包括免疫细胞浸润、免疫评分、免疫检查点、微卫星不稳定性和TIED评分。为了确认KL在ccRCC中的表达情况，我们对ccRCC细胞系和临床组织样本进行了qRT-PCR实验，并比较了正常肾细胞系（HK-2）和ccRCC细胞系ACHN的KL表达水平。最后，我们利用免疫组织化学方法（IHC）评估了组织中KL蛋白的表达水平。在本研究中，我们利用Venn图分析从GSE168845中、导入数据库和MSigDB数据库中鉴定出17个共表达的免疫-衰老相关差异表达基因（IAR-DEGs）。GO和KEGG分析显示，这17个IAR-DEGs的功能主要与“衰老”相关。单变量和多变量Cox分析验证了这17个基因，并确定KL是ccRCC的一个独立预后因子。KL在ccRCC组织中的下调与T期、M期、病理期和组织级别（p < 0.05）呈负相关。这种下调表明疾病恶化和总生存期缩短。我们的校准曲线和预测图显示KL具有出色的预测潜力。GSEA分析显示KL基因介导的免疫和衰老相关通路，与免疫浸润和MS、TIED评分显著相关。进一步的研究揭示了人类肾癌细胞，特别是ccRCC组织中KL mRNA表达水平的显著降低，与邻近正常肾组织相比。此外，免疫组织化学数据显示ccRCC细胞中KL蛋白的表达水平显著降低，与邻近正常组织相比。KL是一种老化相关的免疫治疗潜在靶点，也是一个有效的ccRCC患者的预后生物标志物。© 2023. BioMed Central Ltd., part of Springer Nature.

Clear cell renal cell carcinoma (ccRCC) is a prevalent cancer in adult urology, often leading to metastasis and poor prognosis. Recently, advances in tumor immunology and aging research have opened up new possibilities for the treatment of kidney cancer. Therefore, the identification of potential targets and prognostic biomarkers for immunotherapy has become increasingly urgent.Using GSE168845 data, we identified immune-aging-associated differentially expressed genes (IAR-DEGs) by intersecting differentially expressed immune-related genes and aging-related genes. The prognostic value of IAR-DEGs was determined via univariate and multivariate Cox regression analysis, revealing KL as an independent prognostic factor for ccRCC. We also investigated the correlation between KL and various immune-related factors, including immune cell infiltration, immune score, immune checkpoint, MSI, and TIED score. To confirm the expression of KL in ccRCC, we conducted qRT-PCR assays on both ccRCC cell lines and clinical tissue samples, and compared KL expression levels between normal kidney cell line (HK-2) and ACHN, a ccRCC cell line. Finally, we assessed KL protein expression levels in tissues using immunohistochemistry (IHC).In this study, we utilized Venn diagram analysis to identify 17 co-expressed immune-aging related DEGs from GSE168845, import database, and MSigDB database. GO and KEGG analysis revealed that the functions of the 17 IAR-DEGs were primarily related to "aging". Univariate and multivariate Cox analysis validated these 17 genes, and KL was determined to be an independent prognostic factor for ccRCC. The downregulation of KL was observed in ccRCC tissues and was negatively associated with T stage, M stage, pathological stage, and histologic grade (p < 0.05). This downregulation indicated disease deterioration and a shortened overall survival period. Our calibration curves and nomogram demonstrated the excellent predictive potential of KL. GSEA analysis showed that KL gene mediated immune and aging-related pathways, and was significantly correlated with immune infiltration and MS and TIED score. More research has revealed a significant reduction in KL mRNA expression levels in human renal cancer cells, particularly in ccRCC tissues compared to adjacent normal kidney tissues. Moreover, immunohistochemistry data have demonstrated a marked decrease in KL protein expression levels in ccRCC cells when compared to adjacent normal tissues.KL was a potential aging-related target for immunotherapy and valid prognostic biomarker for ccRCC patients.© 2023. BioMed Central Ltd., part of Springer Nature.