Dataset Information

Genomic analysis uncovers prognostic and immunogenic characteristics of ferroptosis for clear cell renal cell carcinoma.

ABSTRACT: In this study, the characteristic patterns of ferroptosis in clear cell renal cell carcinoma (ccRCC) were systematically investigated with the interactions between ferroptosis and the tumor microenvironment (TME). On the mRNA expression profiles of 57 ferroptosis-related genes (FRGs), three ferroptosis patterns were constructed, with distinct prognosis and immune cell infiltrations (especially T cells and dendritic cells). The high ferroptosis scores were characterized by poorer prognosis, increased T cell infiltration, higher immune and stromal scores, elevated tumor mutation burden, and enhanced response to anti-CTLA4 immunotherapy. Meanwhile, the low ferroptosis scores were distinctly associated with enhanced tumor purity and amino acid and fatty acid metabolism pathways. Following validation, the ferroptosis score was an independent and effective prognostic factor. Collectively, ferroptosis could be involved in the diverse and complex TME. Evaluation of the ferroptosis patterns may heighten the comprehension about immune infiltrations in the TME, assisting oncologists to generate individualized immunotherapeutic strategies.

SUBMITTER: Bai D

PROVIDER: S-EPMC8368772 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomic analysis uncovers prognostic and immunogenic characteristics of ferroptosis for clear cell renal cell carcinoma.

Bai Dan D Feng Huhu H Yang Jiajun J Yin Aiping A Lin Xiao X Qian Airong A Sugiyama Hiroshi H

Molecular therapy. Nucleic acids 20210519

In this study, the characteristic patterns of ferroptosis in clear cell renal cell carcinoma (ccRCC) were systematically investigated with the interactions between ferroptosis and the tumor microenvironment (TME). On the mRNA expression profiles of 57 ferroptosis-related genes (FRGs), three ferroptosis patterns were constructed, with distinct prognosis and immune cell infiltrations (especially T cells and dendritic cells). The high ferroptosis scores were characterized by poorer prognosis, incre ...[more]

PMID: 34458004

Similar Datasets

Project description:BackgroundFerroptosis is a newly defined cell death process triggered by increased iron load and tremendous lipid reactive oxygen species (ROS). Oxidative stress-related ferroptosis is of great important to the occurrence and progression of clear cell renal cell carcinoma (ccRCC), which is particularly susceptibility to ferroptosis agonist. Therefore, exploring the molecular features of ferroptosis and oxidative stress might guide the clinical treatment and prognosis prediction for ccRCC patients.MethodsThe differentially expressed ferroptosis and oxidative stress-associated genes (FPTOSs) between normal renal and ccRCC tissues were identified based on The Cancer Genome Atlas (TCGA) database, and those with prognostic significances were applied to develop a prognostic model and a risk scoring system (FPTOS_score). The clinical parameter, miRNA regulation, tumor mutation burden (TMB), immune cell infiltration, immunotherapy response, and drug susceptibility between two FPTOS-based risk stratifications were determined.ResultsWe have identified 5 prognosis-associated FPTOSs (ACADSB, CDCA3, CHAC1, MYCN, and TFAP2A), and developed a reliable FPTOS_socre system to distinguish patients into low- and high-risk groups. The findings implied that patients from the high-risk group performed poor prognoses, even after stratified analysis of various clinical parameters. A total of 30 miRNA-FPTOS regulatory pairs were recognized to identify the possible molecular mechanisms. Meanwhile, patients from the high-risk group exhibited higher TMB levels than those from the low-risk groups, and the predominant mutated driver genes were VHL, PBRM1 and TTN in both groups. The main infiltrating immune cells of high- and low-risk groups were CD8+ T cells and resting mast cells, respectively, and patients from the high-risk groups showed preferable drug responsiveness to anti-PD-1 immunotherapy. Eventually, potential sensitive drugs (cisplatin, BI-D1870, and docetaxel) and their enrichment pathways were identified to guide the treatment of ccRCC patients with high-risk.ConclusionOur study comprehensively analyzed the expression profiles of FPTOSs and constructed a scoring system with considerable prognostic value, which would supply novel insights into the personalized treatment strategies and prognostic evaluation of ccRCC patient.

Dataset Information

Genomic analysis uncovers prognostic and immunogenic characteristics of ferroptosis for clear cell renal cell carcinoma.

Publications

Genomic analysis uncovers prognostic and immunogenic characteristics of ferroptosis for clear cell renal cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets