Identification and validation of DLX4 as a prognostic and diagnostic biomarker for clear cell renal cell carcinoma

Abstract

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.