High expression of Chitinase 3-like-1 is an unfavorable prognostic factor in urothelial carcinoma of upper urinary tract and urinary bladder

Abstract

BackgroundMetabolic adaptation in cancer cells is important for cancer cell survival. Alternation in cellular metabolism getting more energy to support cell proliferation played a critical role in disease progression. We initially analyzed the public transcriptome of urothelial carcinoma in Gene Expression Omnibus database (GSE31684) with particular focus on genes associated with carbohydrate metabolism, and found that Chitinase 3-like-1 (CHI3L1) was a significantly up-regulated gene associated with advanced disease status. This study was aimed to evaluate the expression and prognostic significance of CHI3L1 in upper urinary tract urothelial carcinoma (UTUC) and urinary bladder urothelial carcinoma (UBUC). Materials and MethodsWe performed immunohistochemical study to evaluate CHI3L1 expression in 2 well-defined cohorts of urothelial carcinoma, including UTUC (n = 340) and UBUC (n = 295). CHI3L1 expression level was determined by H-score method. The associations between CHI3L1 expression and clinicopathological features, disease-specific survival (DSS) and metastasis-free survival (MFS) were analyzed. ResultsHigh expression of CHI3L1 was significantly associated with adverse clinicopathological features in UTUC or UBUC, including advanced tumor status (pT), nodal metastasis, high histological grade, vascular invasion, perineural invasion, and high mitotic activity (all P < 0.05). Kaplan-Meier survival analysis revealed that patients with high CHI3L1 expression had shorter DSS and MFS in both UTUC and UBUC (all P < 0.05). In multivariate survival analyses, high expression of CHI3L1 acted as an independent prognostic factor for worse DSS (P < 0.001 in UTUC and P = 0.036 in UBUC) and MFS (P = 0.002 in UTUC and P = 0.003 in UBUC) in both UTUC and UBUC groups. ConclusionsHigh expression of CHI3L1 was significantly associated with aggressive clinicopathological features and acted as an independent prognostic factor for worse outcome in urothelial carcinoma.