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pmid:36032073

Aging-based molecular classification and score system in ccRCC uncovers distinct prognosis, tumor immunogenicity, and treatment sensitivity.

Maoshu Zhu · Chaoqun Huang · Xinhong Wu · Ying Gu · Xiaoxu Hu · Dongna Ma · Weimin Zhong

Frontiers in immunology · 2022 doi:10.3389/fimmu.2022.877076

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

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Aging-based molecular classification and score system in ccRCC uncovers distinct prognosis, tumor immunogenicity, and treatment sensitivity.
doi
10.3389/fimmu.2022.877076
pmid
36032073
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Maoshu Zhu
[1]
Chaoqun Huang
[2]
Xinhong Wu
[3]
Ying Gu
[4]
Xiaoxu Hu
[5]
Dongna Ma
[6]
Weimin Zhong
journal
Frontiers in immunology
year
2022
abstract
Objective: Aging is a complex biological process and a major risk factor for cancer development. This study was conducted to develop a novel aging-based molecular classification and score system in clear cell renal cell carcinoma (ccRCC). Methods: Integrative analysis of aging-associated genes was performed among ccRCC patients in the TCGA and E-MTAB-1980 cohorts. In accordance with the transcriptional expression matrix of 173 prognostic aging-associated genes, aging phenotypes were clustered with the consensus clustering approach. The agingScore was generated to quantify aging phenotypes with principal component analysis. Tumor-infiltrating immune cells and the cancer immunity cycle were quantified with the ssGSEA approach. Immunotherapy response was estimated through the TIDE algorithm, and a series of tumor immunogenicity indicators were computed. Drug sensitivity analysis was separately conducted based on the GDSC, CTRP, and PRISM analyses. Results: Three aging phenotypes were established for ccRCC, with diverse prognosis, clinical features, immune cell infiltration, tumor immunogenicity, immunotherapeutic response, and sensitivity to targeted drugs. The agingScore was developed, which enabled to reliably and independently predict ccRCC prognosis. Low agingScore patients presented more undesirable survival outcomes. Several small molecular compounds and three therapeutic targets, namely, CYP11A1, SAA1, and GRIK4, were determined for the low agingScore patients. Additionally, the high agingScore patients were more likely to respond to immunotherapy. Conclusion: Overall, our findings introduced an aging-based molecular classification and agingScore system into the risk stratification and treatment decision-making in ccRCC.
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Overall, the agingScore was a reliable prognostic indicator of ccRCC.
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