Clinical Implication of Keratin-15 Quantification for Renal Cell Carcinoma Management: Its Dysregulation and Association with Clinicopathologic Characteristics and Prognostication.

ABSTRACT

Keratin-15 (KRT15) participates in the tumorigenesis of several cancers, especially in urinary tract carcinomas by regulating basal urothelial cell malignant proliferation and differentiation. This study intended to explore the association of KRT15 with tumor features and survival in renal cell carcinoma (RCC) patients. Totally, 210 RCC patients receiving surgical resection were retrospectively enrolled, and then, KRT15 was detected by immunohistochemistry (IHC) assay in the tumor and adjacent tissues. IHC score of KRT15 was increased in tumor tissues versus adjacent tissues (P < 0.001). Meanwhile, KRT15 was associated with RCC occurring in the left kidney (P = 0.024), tumor size > 10 cm (P = 0.035), higher N stage (P = 0.048), and higher tumor-node-metastasis (TNM) stage (P = 0.029). Additionally, high KRT15 (IHC score > 3) estimated poor disease-free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.011). In addition, multivariate regression analysis revealed that high KRT15 [hazard ratio (HR) = 1.719, P = 0.023], higher pathological grade (HR = 1.847, P < 0.001), and higher N stage (HR = 3.447, P < 0.001) were independently related to poor DFS; high KRT15 (HR = 1.796, P = 0.034), eastern cooperative oncology group performance status score (1 vs. 0) (HR = 1.734, P = 0.037), higher pathological grade (HR = 2.045, P < 0.001), and higher N stage (HR = 3.966, P < 0.001) were independently linked to unsatisfactory OS. Furthermore, data from Gene Expression Profiling Interactive Analysis suggested that KRT15 was linked to poor DFS (P = 0.037) and OS (P < 0.001); data from THE HUMAN PROTEIN ATLAS revealed that KRT15 was associated with shorter OS (P < 0.001) in RCC patients. In conclusion, KRT15 is increased in tumor tissues, and correlates with higher tumor stage and larger tumor size, along with poor prognosis for RCC.