AUTHOR=Chen Ji , Tao Qiqi , Lang Zhichao , Jin Yan , Chen Guanqi , Li Xinling , Yu Zhixian , Li Yeping TITLE=Development and validation of a novel necroptosis-related score to improve the outcomes of clear cell renal cell carcinoma JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.967613 DOI=10.3389/fgene.2022.967613 ISSN=1664-8021 ABSTRACT=

Necroptosis has been indicated as a key regulator of tumor progression. However, the prognostic regulatory role of necroptosis in clear cell renal cell carcinoma (ccRCC) needs to be further investigated. In this study, necroptosis-related subtypes were identified by mining the public cohort (n = 530) obtained from The Cancer Genome Atlas. By applying Principal Component Analysis (PCA), the necroptosis-related scores (N-Score) were developed to assess the prognosis procession of ccRCC. The results were further validated by an external clinical cohort (n = 116) obtained from the First Affiliated Hospital of Wenzhou Medical University. It has been found that N-Score could precisely distinguish the prognostic outcomes of patients as an independent risk factor (Hazard ratio = 4.990, 95% confidence interval (CI) = 2.007–12.403, p < 0.001). In addition, changes in N-Score were associated with differences in tumor mutational burden as well as immune infiltration characterization. Moreover, higher N-Scores were also correlated significantly molecular drug sensitivity and stronger immune checkpoint activity. Notably, the prognosis of ccRCC could be effectively guided by combining the N-Scores and external clinical indicators. In conclusion, N-Scores could be served as a robust and effective biomarker to improve the prognosis outcomes and targeted therapy of ccRCC.