Mp39-04 largen Plays Important Roles in Malignant Aggressiveness and Is a Prognostic Factor in Patients With Clear Cell Renal Cell Carcinoma

Abstract

proven with recent genomic or transcriptional analyses. However, it is still difficult to apply these analyses to daily clinical practice owing to economical and practical issues. Here, we established a pathologybased prognostic classification based on the well-validated transcriptional classifier, ClearCorde34, in ccRCC.METHODS: Three-hundred forty-two cases with available tissue were identified and randomly divided into the discovery cohort (n[138) and the validation cohort (n[204). Levels of mRNA were quantified using the Digital Analyzer, and the ccA/ccB subtypes were determined. Histological and immunohistochemistry (IHC) analyses were subsequently performed to establish the pathology-based classification based on the mRNA levels. Finally, the prognostic ability of the new classifier was evaluated in both the discovery and validation cohorts.RESULTS: Of 138 cases in the discovery cohort, 78 (56.5%) and 60 (43.5%) were assigned to the ccA and ccB subtypes, respectively. Proangiogenic genes, neuropilin 1 (NRP1) and regulator of G protein signalling 5 (RGS5), were especially overexpressed in all ccRCC samples and were enriched in ccA-assigned tumours. Histologically, tumour necrosis and the sarcomatoid feature were associated with the ccB subtype. In IHC analyses, expression of NRP1, RGS5, and Forkhead box M1 (FOXM1), an epithelialmesenchymal transition-related factor, significantly correlated with the ccA/ccB subtypes. Combining these three IHC factors and tumour necrosis, we developed the IHC/histology-based classifier, which showed good concordance with the ClearCode34 classifier with an accuracy of 0.80. The established classification significantly stratified relapse-free, cancer-specific, and overall survival rates in both the discovery and validation cohorts.CONCLUSIONS: The novel molecular pathology classifier integrating NRP1, RGS5, FOXM1, and tumour necrosis may enable the stratification of oncological outcomes for patients with ccRCC.