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High PITX1 expression in lung adenocarcinoma patients is associated with DNA methylation and poor prognosis
Authors:Xinyue Song  Chaoran Zhao  Longyang Jiang  Shu Lin  Jia Bi  Qian Wei  Lifeng Yu  Lin Zhao  Minjie Wei
Affiliation:1. Department of Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China;2. Liaoning Key Laboratory of molecular targeted anti-tumor drug development and evaluation, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang City, 110122, Liaoning, China
Abstract:

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 OSin 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, TNFα signaling via NFκB, TGFβ 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.
Keywords:PITX1  pituitary homeobox 1  LUAD  lung adenocarcinoma  NSCLC  non-small cell lung cancer  LUSC  lung squamous cell carcinoma  DNMT  DNAmethyltransferase  OS  overall survival  GSEA  gene set enrichment analysis  Overall survival  DNA methylation  Lung adenocarcinoma
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