# A novel identified epithelial ligand-receptor-associated gene signature highlights POPDC3 as a potential therapy target for non-small cell lung cancer

## TL;DR

This study identifies a new gene signature involving POPDC3 that could serve as a therapy target for non-small cell lung cancer.

## Contribution

The study introduces a novel epithelial ligand-receptor gene signature and identifies POPDC3 as a potential therapeutic target in NSCLC.

## Key findings

- POPDC3 overexpression promotes cancer cell proliferation, migration, invasion, and EMT in NSCLC.
- High POPDC3 expression is linked to increased CD4+ T cell infiltration and PD-1 expression in the tumor microenvironment.
- LRrisk model identifies 20 epithelial ligand-receptor genes with prognostic implications in NSCLC.

## Abstract

The tumor microenvironment (TME) is pivotal in non-small cell lung cancer (NSCLC) progression, influencing drug resistance and immune cell behavior through complex ligand-receptor (LR) interactions. This study developed an epithelial LR-related prognostic risk score (LRrisk) to identify biomarkers and targets in NSCLC. We identified twenty epithelial LRs with significant prognostic implications and delineated three molecular NSCLC subtypes with distinct outcomes, pathological characteristics, biological pathways, and immune profiles. The LRrisk model was constructed using twelve differentially expressed ligand-receptor interaction-related genes (LRGs), with a focus on POPDC3 (popeye domain-containing protein 3), which was overexpressed in NSCLC cells. Functional assays revealed that POPDC3 knockdown reduced cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while its overexpression promoted cancerous activities. In vivo, POPDC3 silencing hindered, and its overexpression accelerated the growth of NSCLC xenografts in nude mice. Additionally, high expression levels of POPDC3 in NSCLC tissues were associated with enhanced CD4+ T cell infiltration and increased PD-1 expression within the TME. Moreover, ectopic POPDC3 overexpression in C57BL/6 J mouse Lewis lung carcinoma (LLC) xenografts enhanced CD4+ T cell infiltration and PD-1 expression in the TME. This research establishes a robust epithelial LR-related signature, highlighting POPDC3 as a critical facilitator of NSCLC progression and a potential therapeutic target.