# Identification and Validation of a Prognostic Model Based on Tumour Necrosis Factor‐Related mRNAs for Kidney Renal Clear Cell Carcinoma

## TL;DR

This study identifies a new model using tumor necrosis factor-related mRNAs to predict survival and guide treatment in kidney cancer.

## Contribution

A novel TRmRNA-based prognostic model for kidney renal clear cell carcinoma is developed and validated.

## Key findings

- A nine TRmRNA signature was identified, with high-risk patients showing significantly shorter survival.
- The model's nomogram achieved 76.6% accuracy in predicting patient outcomes.
- High-risk patients exhibited higher tumor mutational burden and distinct enriched biological pathways.

## Abstract

Tumour necrosis factor (TNF) plays a critical role in tumour progression, but the specific involvement of mRNA in this process, particularly in kidney renal clear cell carcinoma (KIRC) remains insufficiently understood. Our study aims to develop a TNF‐related mRNA (TRmRNA) model to predict prognosis and inform treatment strategies in KIRC. KIRC expression data from The Cancer Genome Atlas (TCGA) and TNF‐related genes (TRGs) from the Genecards database were used to construct and validate a TRmRNA prognostic model. A nomogram integrating clinical features with the risk model was also developed to enhance prognostic accuracy. Enrichment analysis, drug sensitivity analysis and RT‐qPCR validation were performed to further explore the biological mechanisms and clinical applicability of the model. A prognostic signature consisting of nine TRmRNAs was identified. Kaplan–Meier analysis showed that the high‐risk (HRK) group had significantly shorter overall survival (OS) compared to the low‐risk (LRG) group (p < 0.001). The nomogram, incorporating the risk model, yielded an area under the curve (AUC) of 0.766, indicating robust prognostic accuracy. Enrichment analysis identified solute sodium symporter and proximal tubule transport pathways enriched in the LRG group, whereas the HRK group exhibited enrichment in CD22‐mediated BCR regulation and immunoglobulin complex pathways. The HRK group also showed a higher tumour mutational burden (TMB), correlating with a poorer prognosis. RT‐qPCR confirmed the differential expression of mRNAs in KIRC cells. The TRmRNA‐based prognostic model holds significant promise for predicting patient outcomes and guiding personalised treatment strategies in KIRC.