Identifying biomarkers of papillary renal cell carcinoma associated with pathological stage by weighted gene co-expression network analysis

Abstract

// Zhongshi He 1, 2, 3 , Min Sun 1, 3, 4 , Yuan Ke 1, 2, 3 , Rongjie Lin 1, 2, 3 , Youde Xiao 1, 2, 3 , Shuliang Zhou 1, 2, 3 , Hong Zhao 1, 2, 3 , Yan Wang 1, 2, 3 , Fuxiang Zhou 2, 3 , Yunfeng Zhou 2, 3 1 Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, China 2 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China 3 Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China 4 Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China Correspondence to: Fuxiang Zhou, email: happyzhoufx@sina.com Yunfeng Zhou, email: yfzhouwhu@163.com Keywords: papillary renal cell carcinoma (PRCC), the cancer genome atlas (TCGA), weighted gene co-expression network analysis (WGCNA), survival prognosis, pathological stage Received: November 02, 2016      Accepted: February 20, 2017      Published: March 02, 2017 ABSTRACT Although papillary renal cell carcinoma (PRCC) accounts for 10%–15% of renal cell carcinoma (RCC), no predictive molecular biomarker is currently applicable to guiding disease stage of PRCC patients. The mRNASeq data of PRCC and adjacent normal tissue in The Cancer Genome Atlas was analyzed to identify 1148 differentially expressed genes, on which weighted gene co-expression network analysis was performed. Then 11 co-expressed gene modules were identified. The highest association was found between blue module and pathological stage (r = 0.45) by Pearson’s correlation analysis. Functional enrichment analysis revealed that biological processes of blue module focused on nuclear division, cell cycle phase, and spindle (all P < 1e-10). All 40 hub genes in blue module can distinguish localized (pathological stage I, II) from non-localized (pathological stage III, IV) PRCC ( P < 0.01). A good molecular biomarker for pathological stage of RCC must be a prognostic gene in clinical practice. Survival analysis was performed to reversely validate if hub genes were associated with pathological stage. Survival analysis unveiled that all hub genes were associated with patient prognosis ( P < 0.01).The validation cohort GSE2748 verified that 30 hub genes can differentiate localized from non-localized PRCC ( P < 0.01), and 18 hub genes are prognosis-associated ( P < 0.01). ROC curve indicated that the 17 hub genes exhibited excellent diagnostic efficiency for localized and non-localized PRCC (AUC > 0.7). These hub genes may serve as a biomarker and help to distinguish different pathological stages for PRCC patients.