Better prediction of clinical outcome in clear cell renal cell carcinoma based on a 6 metabolism-related gene signature

Scientific Reports · 4 authors, 3 centres

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TL;DR

The signature demonstrated good prognostic prediction ability and was correlated with tumor mutation burden and immune infiltration.

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This study developed a metabolism-related gene (MRG) prognostic risk signature for clear cell renal cell carcinoma (ccRCC) using differentially expressed analysis and WGCNA on TCGA data, followed by univariate Cox and LASSO regression to select hub MRGs. The signature showed good prognostic prediction ability across cohorts. The high-risk group exhibited higher tumor mutation burden, higher immune checkpoint levels (PD-1, LAG3, CTLA4), and elevated plasma cells, M0 macrophages, and Tregs. In vitro, knockdown of PAFAH2 promoted ccRCC cell proliferation and migration.

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cohort

SPECIALTY

oncology

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AI pipeline

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ORIGINAL PAPER

PMC10352344

Better prediction of clinical outcome in clear cell renal cell carcinoma based on a 6 metabolism-related gene signature

Scientific Reports

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ABSTRACT

It has been reported that metabolic disorders participate in the formation and progression of clear cell renal cell carcinoma (ccRCC). However, the predictive value of metabolism-related genes (MRGs) in clinical outcome of ccRCC is still largely unknown. Herein, a novel metabolism-related signature was generated to assess the effect of MRGs on the prognosis of ccRCC patients. Important module MRGs were selected by differentially expressed analysis and WGCNA. Subsequently, the hub MRGs were screened via univariate cox regression as well as LASSO regression. A new metabolism-related signature of 6 hub MRGs (PAFAH2, ACADSB, ACADM, HADH, PYCR1 and ITPKA) was constructed, with a good prognostic prediction ability in the TCGA cohort. The prediction accuracy of this signature was further confirmed in both GSE22541 and FAHWMU cohort. Interestingly, this MRG risk signature was highly correlated with tumor mutation burden and immune infiltration in ccRCC. Notably, lower PAFAH2, a member of 6 MRGs, was found in ccRCC. Knockdown of PAFAH2 contributed to renal cancer cell proliferation and migration. Collectively, a 6-MRG prognostic risk signature is generated to estimate the prognostic status of ccRCC patients, providing a novel insight in the prognosis prediction and treatment of ccRCC.

CITATION EXPORT

Zhixian Yu, Yating Zhan, Yong Guo et al.. Better prediction of clinical outcome in clear cell renal cell carcinoma based on a 6 metabolism-related gene signature. Scientific Reports. (2023). https://doi.org/10.1038/s41598-023-38380-7

AUTHORS

4 · 3 CENTRES

Zhixian Yu, Yating Zhan, Yong Guo, Dalin He

1grid.452438.c0000 0004 1760 8119Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an, 710061 China
2grid.414906.e0000 0004 1808 0918Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
3grid.414906.e0000 0004 1808 0918Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China