High PITX1 expression in lung adenocarcinoma patients is associated with DNA methylation and poor prognosis

Background: Pituitary homeobox 1 (PITX1) is a member of the PITX gene family which is vital to proper development of early embryo. However, the relationship of PITX1 expression and overall survival (OS) in non-small cell lung cancer (NSCLC) is not clear. Methods: In our study, bioinformatic analysis was performed using UCSC Xena Browser. We used data based on the Cancer Genome Atlas-lung cancer (TCGA-LUNG). Kaplan Meier curves of overall survival were used to investigate the association between PITX1 gene expression and OS in NSCLC patients by the UCSC Xena browser. Results: Compared with normal lung tissue, PITX gene family was upregulated in NSCLC. Furthermore, higher PITX1 expression was significantly associated with worse OS in 2 yrs., 5 yrs. and 10 yrs. OS (p = 0.004754, 0.01469, 0.02935 respectively) in lung adenocarcinoma (LUAD) patients, but not in lung squamous cell carcinoma (LUSC) patients. PITX1 expression increased in male patients, advanced TNM stage, advanced T stage and advanced regional lymph node status of LUAD patients. PITX1 expressed lowest in bronchioid subtype, meanwhile PITX1 expression was highest in squamoid and magnoid subtype. The high DNA methylation of PITX1 indicated the poor OS in LUAD patients. GSEA revealed that inflammatory response, TNF alpha signaling via NE kappa B, TGF beta signaling, IL6 JAK STAT3 signaling and interferon Gamma response were significantly enriched in high PITX1 expression. Conclusion: These findings suggested that PITX1 might serve as a potential biomarker for early detection and prognosis prediction of LUAD patients.