# Systematically identification of survival-associated eQTLs in a Japanese kidney cancer cohort

## TL;DR

This study identifies genetic variants linked to survival in Japanese kidney cancer patients and validates them in an international cohort, revealing potential biomarkers for prognosis.

## Contribution

First study to explore eQTLs' prognostic value in an Asian ccRCC cohort and identify cross-population survival-associated variants.

## Key findings

- Identified 9 eGenes significantly associated with overall survival in Japanese ccRCC patients.
- 223 eQTLs regulating 54 eGenes showed consistent prognostic effects across expression and genetic levels.
- Eight eQTLs regulating 11 eGenes demonstrated reproducible survival associations across ethnicities.

## Abstract

Clear cell renal carcinoma (ccRCC) is the predominant form of kidney cancer, but the prognostic value of expression quantitative trait loci (eQTLs) remains underexplored, particularly in Asian populations.

We analyzed whole-exome sequencing and RNA sequencing data from 100 Japanese ccRCC patients to identify eQTLs. Multiple Cox proportional hazard models assessed survival associations, with validation in the Cancer Genome Atlas ccRCC cohort (n = 287).

We identified 805 eGenes and 4,558 cis-eQTLs in the Japanese cohort. Survival analysis revealed a total of 9 eGenes significantly associated with overall survival (FDR < 0.05). Further exploratory analysis were performed using 158 eGenes and 711 eQTLs (p-value <0.05) as potential prognostic signals. Among these, 223 eQTLs regulating 54 eGenes showed consistent prognostic effects at both expression and genetic levels. Cross-population validation identified eight eQTLs regulating 11 eGenes with reproducible survival associations across ethnicities, including a missense mutation in ERV3–1 and regulatory variants near ANKRD20A7P. These variants demonstrated consistent allelic effects on both gene expression and patient survival in both cohorts.

Clear cell renal carcinoma (ccRCC) is the most common type of kidney cancer, but effective targeted therapies and reliable tools to predict patient outcomes are still limited. In this study, we explored how inherited genetic differences influence gene activity and survival in patients with ccRCC. Specifically, we focused on genetic variants known as expression quantitative trait loci (eQTLs), which affect how much certain genes are expressed. Our research is the first to examine the prognostic value of these eQTLs in an Asian patient population. By analyzing genomic and gene expression data from Japanese patients, and then validating our findings in an independent international cohort from The Cancer Genome Atlas (TCGA), we identified several genetic variants that are consistently associated with patient prognosis across populations. Notably, we discovered a variant in the ERV3–1 gene that alters the protein structure, as well as regulatory variants near genes like ANKRD20A7P that may influence cancer progression. These findings provide new insights into the genetic architecture of ccRCC and suggest potential biomarkers that warrant further investigation.