Construction and validation of a novel ten miRNA-pair based signature for the prognosis of clear cell renal cell carcinoma

Yulin Wang; Ziyan Shen; Shaocong Mo; Leijie Dai; Biao Song; Wenchao Gu; Xiaoqiang Ding; Xiaoyan Zhang

doi:10.1016/j.tranon.2022.101519

Construction and validation of a novel ten miRNA-pair based signature for the prognosis of clear cell renal cell carcinoma

Transl Oncol. 2022 Nov:25:101519. doi: 10.1016/j.tranon.2022.101519. Epub 2022 Aug 20.

Authors

Yulin Wang¹, Ziyan Shen², Shaocong Mo³, Leijie Dai⁴, Biao Song⁵, Wenchao Gu⁶, Xiaoqiang Ding⁷, Xiaoyan Zhang⁸

Affiliations

¹ Department of Nephrology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China; Shanghai Medical Center of Kidney Disease, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China.
² Department of Nephrology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China; Shanghai Medical Center of Kidney Disease, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, No. 136 Medical College Road, Shanghai 200032, China.
³ Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
⁴ Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
⁵ Department of Dermatology, Peking Union Medical College Hospital, Beijing, 100005, China.
⁶ Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, 371-8511, Japan.
⁷ Department of Nephrology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China; Shanghai Medical Center of Kidney Disease, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, No. 136 Medical College Road, Shanghai 200032, China. Electronic address: ding.xiaoqiang@zs-hospital.sh.cn.
⁸ Department of Nephrology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China; Shanghai Medical Center of Kidney Disease, Shanghai 200032, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai 200032, China; Shanghai Institute of Kidney and Dialysis, No. 136 Medical College Road, Shanghai 200032, China. Electronic address: zhang.xiaoyan@zs-hospital.sh.cn.

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) is the most predominate pathological subtype of renal cell carcinoma, causing a recurrence or metastasis rate as high as 20% to 40% after operation, for which effective prognostic signature is urgently needed.

Methods: The mRNA and miRNA profiles of ccRCC specimens were collected from the Cancer Genome Atlas. MiRNA-pair risk score (miPRS) for each miRNA pair was generated as a signature and validated by univariate and multivariate Cox proportional hazards regression analysis. Functional enrichment was performed, and immune cells infiltration, as well as tumor mutation burden (TMB), and immunophenoscore (IPS) were evaluated between high and low miPRS groups. Target gene-prediction and differentially expressed gene-analysis were performed based on databases of miRDB, miRTarBase, and TargetScan. Multivariate Cox proportional hazards regression analysis was adopted to establish the prognostic model and Kaplan-Meier survival analysis was performed.

Findings: A novel 10 miRNA-pair based signature was established. Area under the time-dependent receiver operating curve proved the performance of the signature in the training, validation, and testing cohorts. Higher TMB, as well as the higher CTLA4-negative PD1-negative IPS, were discovered in high miPRS patients. A prognostic model was built based on miPRS (1 year-, 5 year-, 10 year- ROC-AUC=0.92, 0.84, 0.82, respectively).

Interpretation: The model based on miPRS is a novel and valid tool for predicting the prognosis of ccRCC.

Funding: This study was supported by research grants from the China National Natural Scientific Foundation (81903972, 82002018, and 82170752) and Shanghai Sailing Program (19YF1406700 and 20YF1406000).

Keywords: Bioinformatics; Immune; Prognosis; Signature; ccRCC; miRNA-pair.