Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma

Abstract

Kidney renal clear cell carcinoma (KIRC) has high morbidity and gradually increased in recent years, and the rate of progression once relapsed is high. At present, owing to lack of effective prognosis predicted markers and post-recurrence drug selection guidelines, the prognosis of KIRC patients is greatly affected. Necroptosis is a regulated form of cell necrosis in a way that is independent of caspase. Induced necroptosis is considered an effective strategy in chemotherapy and targeted drugs, and it can also be used to improve the efficacy of immunotherapy. Herein, we quantified the necroptosis landscape of KIRC patients from The Cancer Genome Atlas (TCGA) database and divided them into two distinct necroptosis-related patterns (C1 and C2) through the non-negative matrix factorization (NMF) algorithm. Multi-analysis revealed the differences in clinicopathological characteristics and tumor immune microenvironment (TIME). Then, we constructed the NRG prognosis signature (NRGscore), which contained 10 NRGs (PLK1, APP, TNFRSF21, CXCL8, MYCN, TNFRSF1A, TRAF2, HSP90AA1, STUB1, and FLT3). We confirmed that NRGscore could be used as an independent prognostic marker for KIRC patients and performed excellent stability and accuracy. A nomogram model was also established to provide a more beneficial prognostic indicator for the clinic. We found that NRGscore was significantly correlated with clinicopathological characteristics, TIME, and tumor mutation burden (TMB) of KIRC patients. Moreover, NRGscore had effective guiding significance for immunotherapy, chemotherapy, and targeted drugs.

Identification of a Necroptosis-Related Prognostic Index and Associated Regulatory Axis in Kidney Renal Clear Cell Carcinoma

“…Moreover, we further analyzed the prognostic outcomes of patients with various clinical stage and pathological grade. Compared with another study, 17 we used a smaller number of genes to construct a prognostic signature, which would be beneficial to clinical application and promotion, and also had higher clinical utility. Of importance, we not only analyzed the relationship between NPRI and the expression of immune checkpoints, but also performed TIDE analysis, which was currently recognized as an ideal method for predicting the efficacy of immunotherapy.…”

Establishment of a Necroptosis-Related Prognostic Signature to Reveal Immune Infiltration and Predict Drug Sensitivity in Hepatocellular Carcinoma

“…PLK1 knockout suppressed cancer cell survival, induced apoptosis, and increased the sensitivity to chemotherapy drugs ( Reagan-Shaw and Ahmad, 2005 ; Weiss and Efferth, 2012 ). Moreover, PLK was identified as one of the necroptosis-related prognosis genes of invasive breast carcinoma ( Hu et al, 2022 ) and clear cell renal cell carcinoma ( Xin et al, 2022 ). In addition, PLK1 mediated the phosphorylation of RIPK3 by directly associated with RIPK3 as cell enter mitosis ( Gupta and Liu, 2021 ).…”

Construction of a Necroptosis-Associated Long Non-Coding RNA Signature to Predict Prognosis and Immune Response in Hepatocellular Carcinoma

“…As an alternative mode of programmed cell death, necroptosis overcomes apoptosis resistance and may trigger and amplify anti-tumor immunity in cancer therapy ( Gong et al, 2019 ). Further, necroptosis is not only an important cellular process that regulates the evolution of cancer, but is also closely associated with the prognosis of many tumors ( Lim et al, 2021 ; Xin et al, 2022 ). In HCC, necroptosis driver genes correlate with tumor-infiltrating lymphocyte density, with CD8 + T cells clustering in tumors with higher expression of necroptosis-related genes ( Nicolè et al, 2022 ).…”