SERPINH 1 overexpression in clear cell renal cell carcinoma: association with poor clinical outcome and its potential as a novel prognostic marker

Precision therapy for clear cell renal cell carcinoma (cc RCC ) requires molecular biomarkers ascertaining disease prognosis. In this study, we performed integrated proteomic and transcriptomic screening in all four tumour‐node‐metastasis stages of cc RCC and adjacent normal tissues ( n  =   18) to investigate differentially expressed genes. Most identified differentially expressed genes revealed a strong association with transforming growth factor‐β level and the epithelial‐to‐mesenchymal transition process. Of them, Serpin peptidase inhibitor clade H member 1 ( SERPINH 1) revealed the strongest association with poor prognosis and regulation on the expression levels of epithelial‐to‐mesenchymal transition markers. Subsequently, two independent sets ( n  =   532 and 105) verified the high level of SERPINH 1 in cc RCC tissues and its association with reduced overall survival and disease‐free survival in all tumour‐node‐metastasis stages and patients with von Hippel–Lindau wild‐type ( VHL ‐ WT ). SERPINH 1 was an independent predictor of poor overall survival (hazard ratio 0.696 for all patients) and disease‐free survival (hazard ratio 0.433 for all patients and 0.362 for patients with VHL ‐ WT ) in cc RCC . We have thus shown for the first time that SERPINH 1 is an independent precision predictor for unfavourable prognosis in cc RCC . This could assist in identifying patients who need early aggressive management and deepen our understanding of the pathogenesis of VHL ‐ WT cc RCC .