# A Cytokine-Related Gene Signature for Pan-Cancer Prognostic Stratification and Malignant Phenotype Characterization

## TL;DR

This study identifies a 16-gene cytokine-related signature that predicts cancer prognosis across multiple tumor types and is linked to aggressive tumor traits.

## Contribution

A novel pan-cancer cytokine-related gene signature is developed for prognostic stratification and malignant phenotype characterization.

## Key findings

- A 16-gene cytokine-related signature consistently stratifies patients into high- and low-risk groups across multiple cancer types.
- High risk scores correlate with poor survival and are associated with cell cycle activity, epithelial-mesenchymal transition, and extracellular matrix remodeling.
- Risk-associated genes like PANX1 and FRMD8 show increased protein expression in tumor tissues compared to normal tissues.

## Abstract

Cytokines are central regulators of inflammation and immune responses within the tumor microenvironment and have been implicated in cancer progression and prognosis. However, the prognostic value of coordinated cytokine-related transcriptional programs across cancer types has not been systematically explored. Pan-cancer transcriptomic and clinical data were analyzed to construct a cytokine-related prognostic signature using least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were stratified into high-risk and low-risk groups based on the derived risk score. Prognostic performance was evaluated in training and test cohorts, and biological relevance was assessed through survival analyses and pathway-level investigations. A 16-gene cytokine-related signature was established that consistently stratified patients into distinct prognostic groups across multiple cancer types. High cytokine-related risk scores were significantly associated with unfavorable survival outcomes and were linked to enhanced cell cycle activity, epithelial-mesenchymal transition, and extracellular matrix remodeling. Integration of the risk score with clinical variables improved individualized survival prediction. Immunohistochemical analyses further confirmed increased protein expression of representative risk-associated genes, including pannexin 1 (PANX1) and FERM domain containing 8 (FRMD8), in multiple tumor tissues compared with corresponding normal tissues. The cytokine-related prognostic signature captures key inflammatory and immune-related programs underlying tumor aggressiveness and provides a robust tool for pan-cancer risk stratification with potential clinical utility.