Shared inflammatory-metabolic transcriptional effects in tubulointerstitial fibrosis and clear cell renal cell carcinoma.
- 1Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, PR China.
- 2Department of Nephrology, the Key Laboratory for the Prevention and Treatment of Kidney Disease of Chongqing, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, PR China. Electronic address: [email protected].
Abstract
Background
Renal tubulointerstitial fibrosis and clear cell renal cell carcinoma (ccRCC) are distinct diseases that both exhibit inflammatory and metabolic remodeling. We investigated whether independently analyzed human fibrosis and ccRCC transcriptomes show reproducible disease-associated transcriptional overlap.Methods
TCGA-KIRC (533 primary tumors and 72 solid-tissue normal samples) and GSE12682 (23 fibrosis and 13 healthy tubulointerstitial samples) were analyzed independently before gene-symbol alignment. Shared effects required FDR < 0.05, absolute log2 fold change ≥ 0.5, and concordant disease-associated direction. GSE328575 (65,770 cells) was used for descriptive single-cell localization. Species-resolved RT-qPCR assessed HADHA, ACSL4, PPARA, and PPARGC1A in TGF-β1-treated HK-2 and NRK-52E cells and in 786-O versus HK-2 cells.Results
Among 11,805 aligned genes, 6690 (56.7%) showed concordant directions and 64 met the full shared-effect criteria, including 51 shared-upregulated and 13 shared-downregulated genes. Genome-wide effects were modestly but significantly correlated (Spearman ρ=0.224, P = 1.05×10⁻¹³³). Both diseases showed increased inflammatory and reduced fatty-acid-oxidation programs; S100A9 was the only independently shared member of the curated candidate panel. RT-qPCR showed decreased HADHA, PPARA, and PPARGC1A and increased ACSL4 across both TGF-β1-treated tubular models and 786-O versus HK-2 cells.Conclusions
Human bulk-tissue analyses identified a reproducible but limited inflammatory-metabolic overlap between fibrosis and ccRCC, with experimental mRNA-level validation of selected metabolic genes. The findings do not establish causality, direct HADHA-ACSL4 regulation, ferroptosis execution, or treatment efficacy.
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BibTeX
@article{tang2026shared,
title = {{Shared inflammatory-metabolic transcriptional effects in tubulointerstitial fibrosis and clear cell renal cell carcinoma.}},
author = {Sha Tang and Furong Li and Ling Nie and Yinghui Huang and Yiqin Wang and Jinghong Zhao and Yan Li},
journal = {Translational oncology},
year = {2026},
month = oct,
doi = {10.1016/j.tranon.2026.103057},
url = {https://europepmc.org/article/MED/42854358},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Shared inflammatory-metabolic transcriptional effects in tubulointerstitial fibrosis and clear cell renal cell carcinoma.
AU - Sha Tang
AU - Furong Li
AU - Ling Nie
AU - Yinghui Huang
AU - Yiqin Wang
AU - Jinghong Zhao
AU - Yan Li
PY - 2026
DA - 2026/10/09
JO - Translational oncology
DO - 10.1016/j.tranon.2026.103057
UR - https://europepmc.org/article/MED/42854358
AB - Background Renal tubulointerstitial fibrosis and clear cell renal cell carcinoma (ccRCC) are distinct diseases that both exhibit inflammatory and metabolic remodeling. We investigated whether independently analyzed human fibrosis and ccRCC transcriptomes show reproducible disease-associated transcriptional overlap.Methods TCGA-KIRC (533 primary tumors and 72 solid-tissue normal samples) and GSE12682 (23 fibrosis and 13 healthy tubulointerstitial samples) were analyzed independently before gene-symbol alignment. Shared effects required FDR < 0.05, absolute log2 fold change ≥ 0.5, and concordant disease-associated direction. GSE328575 (65,770 cells) was used for descriptive single-cell localization. Species-resolved RT-qPCR assessed HADHA, ACSL4, PPARA, and PPARGC1A in TGF-β1-treated HK-2 and NRK-52E cells and in 786-O versus HK-2 cells.Results Among 11,805 aligned genes, 6690 (56.7%) showed concordant directions and 64 met the full shared-effect criteria, including 51 shared-upregulated and 13 shared-downregulated genes. Genome-wide effects were modestly but significantly correlated (Spearman ρ=0.224, P = 1.05×10⁻¹³³). Both diseases showed increased inflammatory and reduced fatty-acid-oxidation programs; S100A9 was the only independently shared member of the curated candidate panel. RT-qPCR showed decreased HADHA, PPARA, and PPARGC1A and increased ACSL4 across both TGF-β1-treated tubular models and 786-O versus HK-2 cells.Conclusions Human bulk-tissue analyses identified a reproducible but limited inflammatory-metabolic overlap between fibrosis and ccRCC, with experimental mRNA-level validation of selected metabolic genes. The findings do not establish causality, direct HADHA-ACSL4 regulation, ferroptosis execution, or treatment efficacy.
SN - 1936-5233
ER -