# A PDCD4-Based Gene Expression Signature Predicts Overall Survival in Renal Cell Carcinoma: A TCGA-Based Discovery and External Validation Study

## TL;DR

A new gene expression signature based on PDCD4 can predict survival outcomes in kidney cancer patients, validated across multiple datasets.

## Contribution

A novel PDCD4-based gene expression signature was developed and validated for predicting overall survival in renal cell carcinoma.

## Key findings

- Low PDCD4 signature scores correlate with worse overall survival (HR = 2.17) in renal cell carcinoma patients.
- The signature remains an independent prognostic factor after adjusting for clinical variables (HR = 1.57).
- The signature consistently predicts survival across multiple independent validation cohorts.

## Abstract

Renal cell carcinoma (RCC) is a heterogeneous disease with variable clinical outcomes. PDCD4 functions as a tumor suppressor, but its role in RCC prognosis remains unclear. We aimed to develop and validate a PDCD4-based gene expression signature for predicting overall survival in RCC. We analyzed RNA-seq data from 541 clear cell RCC patients in The Cancer Genome Atlas (TCGA-KIRC). We identified 100 genes (50 positively and 50 negatively correlated with PDCD4) to create a prognostic signature. Patients were stratified into high- and low-signature groups using median cutoff. Kaplan–Meier analysis and Cox regression models assessed prognostic value. External validation was performed in four independent cohorts: GSE29609, GSE73731, GSE53757, and GSE40435. Low PDCD4 signature scores were associated with significantly worse overall survival (HR = 2.17, 95% CI: 1.58–2.98, p < 0.001) and advanced tumor stage. The median survival difference was approximately 46 months. In multivariate analysis adjusting for age, gender, stage, and grade, the signature remained an independent prognostic factor (HR = 1.57, 95% CI: 1.11–2.22, p = 0.011). The signature demonstrated consistent prognostic patterns across platforms, with high signature scores associated with early-stage disease and low-grade tumors, and with potential clinical utility for risk stratification and treatment planning.