Wang Jiawei, Tao Liangjun, Liu Yingqing, Liu Heqian, Shen Xudong, Tao Lingsong
Department of Urology, The Second People's Hospital of Wuhu, Wuhu, Anhui 241000, P.R. China.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Oncol Lett. 2023 Feb 28;25(4):146. doi: 10.3892/ol.2023.13732. eCollection 2023 Apr.
Clear cell renal cell carcinoma (ccRCC) is a lethal cancer, and biomarkers for exact diagnosis and predicting prognosis are urgently needed. The present study aimed to determine the roles of distal-less homeobox (DLX) family genes in ccRCC. The clinicopathological and mRNA expression data of patients with ccRCC were derived from The Cancer Genome Atlas database. Kaplan-Meier curves, univariate and multivariate Cox hazard analyses, in addition to receiver operator characteristic curves were used to evaluate the prognostic and diagnostic values. A single-sample gene set enrichment analysis was used to quantify the infiltration levels of immune cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were conducted to examine the expression levels of DLX4 in tumor and adjacent tissue; the results demonstrated that DLX4 was highly expressed in ccRCC tissues compared with normal renal tissues. Furthermore, DLX4 expression was associated with tumor stage and grade. High proportions of males, advanced pathological stage, higher tumor grade and T, N and M stage were also observed in the high DLX4 expression group. Patients with the high DLX4 expression levels tended to have lower overall survival and disease-free survival rates compared with those with low DLX4 expression. DLX4 expression also showed favorable diagnostic efficiency in ccRCC patients. Based on functional enrichment analysis, cell cycle related pathways, epithelial-mesenchymal transition, glycolysis and inflammatory response were associated with the expression levels of DLX4. Furthermore, DLX4 expression was revealed to be associated with tumor immunosuppressive microenvironment. Overall, the expression level of DLX4 may be considered a novel prognostic indicator in ccRCC and a specific diagnostic biomarker for patients with ccRCC.
透明细胞肾细胞癌（ccRCC）是一种致命性癌症，迫切需要用于准确诊断和预测预后的生物标志物。本研究旨在确定远端缺失同源框（DLX）家族基因在ccRCC中的作用。ccRCC患者的临床病理和mRNA表达数据来自癌症基因组图谱数据库。采用Kaplan-Meier曲线、单因素和多因素Cox风险分析以及受试者工作特征曲线来评估预后和诊断价值。使用单样本基因集富集分析来量化免疫细胞的浸润水平。进行逆转录定量聚合酶链反应（RT-qPCR）和免疫组织化学检测肿瘤组织和癌旁组织中DLX4的表达水平；结果表明，与正常肾组织相比，DLX4在ccRCC组织中高表达。此外，DLX4表达与肿瘤分期和分级相关。在DLX4高表达组中还观察到男性比例高、病理分期晚、肿瘤分级高以及T、N和M分期高。与DLX4低表达患者相比，DLX4高表达水平的患者总生存率和无病生存率往往较低。DLX4表达在ccRCC患者中也显示出良好的诊断效能。基于功能富集分析，细胞周期相关通路、上皮-间质转化、糖酵解和炎症反应与DLX4表达水平相关。此外，DLX4表达与肿瘤免疫抑制微环境相关。总体而言，DLX4的表达水平可被视为ccRCC的一种新型预后指标以及ccRCC患者的一种特异性诊断生物标志物。
