# FGF2 as a Potential Tumor Suppressor in Lung Adenocarcinoma

## TL;DR

This study suggests that FGF2, a protein previously linked to cancer in conflicting ways, may act as a tumor suppressor in lung adenocarcinoma, potentially serving as a biomarker for monitoring cancer progression.

## Contribution

The novel contribution is the identification of FGF2 as a tumor suppressor in LUAD, supported by multi-dataset analysis and in vitro experiments.

## Key findings

- FGF2 is consistently downregulated in LUAD tissues across multiple datasets and stages.
- Higher FGF2 expression correlates with better overall and progression-free survival in LUAD patients.
- Exogenous FGF2 treatment suppresses LUAD cell migration and wound healing in vitro.

## Abstract

Background/Objectives: Lung adenocarcinoma (LUAD), the predominant subtype of non-small cell lung cancer (NSCLC), is frequently diagnosed at advanced stages with distant metastasis, underscoring the need for effective prognostic biomarkers. Fibroblast growth factor 2 (FGF2), a multifunctional regulator, has shown to play contradictory roles in cancer progression. Methods: We analyzed three independent Gene Expression Omnibus (GEO) datasets (GSE19804, GSE18842, and GSE19188) to identify consistently dysregulated genes in LUAD. Functional enrichment (GO, KEGG, and cancer hallmark analysis), protein–protein interaction (PPI) network construction, and hub gene prioritization were performed using public bioinformatic tools. Survival analyses were conducted via the Kaplan–Meier Plotter. The expression of FGF2 was validated across multiple platforms, including TCGA, CPTAC, TNMplot, LCE, and the Human Protein Atlas. Functional assays (Transwell migration and wound healing) demonstrated that exogenous FGF2 significantly suppressed LUAD cell motility in vitro. Results: A total of 949 differentially expressed genes (DEGs) were commonly identified across datasets, with enrichment in cell adhesion and metastasis-related pathways. Among the 11 hub genes identified, FGF2 was consistently downregulated in LUAD tissues across all datasets and stages. Higher FGF2 expression was associated with longer overall and progression-free survival. In vitro, FGF2 treatment significantly suppressed the migration and wound healing abilities of LUAD cell lines. Conclusions: FGF2 is downregulated in LUAD and inversely associated with metastatic progression and poor prognosis. The observed reduction in cancer cell motility upon FGF2 treatment in vitro, together with its expression pattern, supports a potential tumor-suppressive role and suggests that FGF2 may serve as a candidate non-invasive biomarker for monitoring LUAD metastasis.