GPX4 predicts poor prognosis and regulates tumor proliferation and senescence in colorectal adenocarcinoma.

Background: Colorectal adenocarcinoma (COAD) is one of the most common gastrointestinal malignancies. There is a pressing need to recognize reliable biomarkers that can improve diagnostic accuracy, predict prognosis, and serve as effective molecular targets. Glutathione peroxidase 4 (GPX4) is an important antioxidant protein. Evidence demonstrates that abnormal expression of GPX4 is related to cancer initiation and progression. However, the role of GPX4 in COAD remains unclear.

Methods: We employed bioinformatics analysis and conducted subsequent validation of biological processes, including cell counting kit-8 assay (CCK-8), colony formation assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), 5-ethynyl-2'-deoxyuridine assay (EdU), western blot, immunohistochemistry, senescence associated β-galactosidase (SA-β-gal) staining and immunofluorescence to explore the expression status, prognostic value and biological function of GPX4 in COAD.

Results: Our data revealed that GPX4 mRNA expression was upregulated in COAD tissues and could predict the prognosis in patients with COAD. High GPX4 expression was associated with increased infiltration of malignant cells. We also performed a series of cell experiments confirming that GPX4 knockdown inhibited proliferation and induced cellular senescence, as determined by using CCK-8, colony formation, and EdU assay. In addition, SA-β-gal staining and senescence-associated secretory phenotype (SASP) components, such as P21 and Interleukin-6 (IL-6), were increased in GPX4 knockdown cells, while Lamin B1 was decreased. Moreover, we predicted that high expression of GPX4 was related to low immune cell infiltration.

Conclusion: This study demonstrates that GPX4 is a potential prognostic biomarker and target gene for COAD.