Background: Urothelial carcinoma (UC) is a common cancer in industrialized country. UC of urinary bladder (UCUB) and of upper urinary tract (UCUT) may share similar tumorigenesis. Previously, genome-wide association studies identifi ed that genetic variation of solute carrier family 14 transporters, member 1 (SLC14A1) is associated with bladder cancer development. By using public domain datasets and our well-characterized cohort, we intended to analyze the association of SLC14A1 expression in UCUB and UCUT.Design: Two datasets from GEO (GSE31684 and GSE32894) were selected and analyzed to examine the signifi cance of SLC14A1 transcript expression in relation to primary tumor (pT) status. SLC14A1 transcript levels were further validated by using Quantigene assay in 35 and 40 UBUC and UTUC cases respectively, and were further correlated with various clincopathological factors. SLC14A1 immunostain was performed on 340 cases of UCUT and 295 cases of UBUC and interpreted by using H-score. The immunoexpression was then correlated with clinicopathological features, disease-specifi c survival (DSS), and metastasis-free survival (MeFS).Results: Validation of SLC14A1 transcript in public domain datasets showed a stepwise down-regulation during UCUB progression, which is also confi rm by using Quantigene assay in our cohort. In the immunohistochemical study, loss of SLC14A1 expression in both groups of UCs signifi cantly associated with advanced pT stage (both p <0.001), lymph node metastasis (both p <0.001), high histological grade (both p <0.001), vascular invasion (both p <0.001), perineurial invasion (UCUT, p =0.002; UCUB, p =0.021), and frequent mitosis (both p =0.003). Loss of SLC14A1 expression also independently predicted poor DSS (UCUT p =0.033; UCUB p =0.005) and MeFS (UCUT p =0.012; UCUB p =0.031) in both groups of patients.Conclusions: SLC14A1 down-regulation is associated with advanced tumor stage and conferred poorer clinical outcome, justifying that SLC14A1 is a potential prognostic biomarker of UC.
