Abstract 1274: Integrated multiomics analysis identifies defective CoQ10 interactome in human kidney cancers.

作者：Gregory M. Miller, Nischal Mahaveer Chaud, Catarina M. Quinzi, Brian Berman, Vivek K. Vishnudas, Vijay Modur, Vlatcheslav Akmaev, Niven R. Narain, Stéphane Gesta, Michael A. Kiebish · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.am2026-1274 · 研究领域：Coenzyme Q10 studies and effects、Genetic and Kidney Cyst Diseases、ATP Synthase and ATPases Research

Abstract Defective energy metabolism has been established as a hallmark of cancer; however, the specific genetic basis underlying this relationship across cancers remains unclear. Ubiquinone (CoQ10) plays an essential role in regulating efficient generation of mitochondrial ATP and reactive oxygen species levels. Multi-omics assessment of the CoQ10 biosynthesis pathway genes in The Cancer Genome Atlas Program (TCGA) revealed Kidney Clear Cell Carcinoma (KIRC) and Kidney Papillary renal cell carcinoma (KIRP) as cancers that demonstrated a significant relationship between poor prognosis and low expression or copy number deletions in the CoQ10 biosynthesis genes. However, the link between deletions and low expression in CoQ10 biosynthesis genes and poor outcomes remains unknown. Towards this aim, we defined the CoQ10 interactome as a set of 37 protein encoding genes that bind with CoQ10, along with enzymes involved in downstream pathways impacted by CoQ10 homeostasis, based on literature review. We then investigated this CoQ10 interactome for their association with outcomes for KIRC and KIRP patients in TCGA datasets. First, patients were grouped into low/high expression groups based on median gene expression levels for the indication. We then investigated the association of outcome measures Overall Survival (OS) and Progression Free Interval (PFI) with expression groups in KIRC (n=530) and KIRP (n=288) patients. Our results found that low gene expression in 21 of 37 CoQ10 inter...