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.
Highlights
Kidney cancer is the third largest malignant tumor in the genitourinary system, with growing morbidity and mortality in recent years
Single-sample gene set enrichment analysis, ESTIMATE, and CIBERSORT were used in R to assess the tumor immune microenvironment (TIME) status of each Kidney renal clear cell carcinoma (KIRC) sample. ssGSEA investigated congenital and adaptive immune cells as well as a variety of immune-related functions
The chemotherapeutic response of KIRC patients was evaluated by Genomics of Drug Sensitivity in Cancer (GDSC)
Summary
Kidney cancer is the third largest malignant tumor in the genitourinary system, with growing morbidity and mortality in recent years. About 90% of kidney cancer was renal cell carcinoma (RCC), 70% of which was kidney renal clear cell carcinoma (KIRC) (Atkins and Tannir, 2018). With advances in RCC pathologic staging, the 5-year disease-specific survival (DSS) rate has been reduced by about 10%; the median overall survival (OS) for advanced. Medication (immunotherapy, chemotherapy, and targeted drugs) is the preferred treatment approach for patients with end-stage or recurrent KIRC. The tumor microenvironment (TME) is closely related to tumor progression and efficacy of immunotherapy and chemotherapy (Wu and Dai, 2017; Hinshaw and Shevde, 2019; Newton et al, 2019). Altering the TME has been a potential strategy for improving the efficacy of anticancer treatments and clinical outcomes
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