# Integrated analysis identifies P4HA2 as a key regulator of STAT1-mediated colorectal cancer progression and a potential biomarker for precision therapy

## TL;DR

This study shows that P4HA2 promotes colorectal cancer growth and weakens the immune response by controlling the STAT1/PD-L1 pathway, suggesting it could be a new target for treatment.

## Contribution

The study identifies P4HA2 as a novel regulator of the STAT1/PD-L1 pathway in colorectal cancer progression.

## Key findings

- High P4HA2 expression correlates with advanced cancer stages and poor prognosis in CRC.
- P4HA2 promotes cancer cell proliferation and migration in functional assays.
- P4HA2 downregulates STAT1, modulating the STAT1/PD-L1 pathway to suppress anti-tumor immunity.

## Abstract

P4HA2 is implicated in regulating tumor microenvironment formation and may play roles in inflammation and tumor immunity. However, its mechanistic involvement in colorectal cancer (CRC) remains largely unexplored.

We analyzed P4HA2 expression in CRC tissues and correlated it with clinicopathological features. Functional assays (CCK8, wound healing, Transwell) were performed to assess proliferation and migration. Proteomic analysis identified downstream targets, with STAT1/PD-L1 pathway validation.

High P4HA2 expression correlated with advanced T/M stages and served as an independent poor prognostic factor. Functional experiments confirmed P4HA2's role in promoting CRC proliferation and migration. Mechanistically, P4HA2 bound to and downregulated STAT1, subsequently modulating the STAT1/PD-L1 pathway.

Our findings reveal P4HA2 promotes CRC progression and suppresses anti-tumor immunity via STAT1/PD-L1 axis regulation. This study uncovers a novel pathogenic mechanism, positioning P4HA2 as a potential therapeutic target in CRC.