Clinical Significance Of PITX1 Gene In Non-small Cell Lung Cancer Based On Bioinformatics Analysis

Objective: Lung cancer is one of the most common malignant tumor diseases,and its incidence and mortality are the highest in the world,exceeding one-tenth of the incidence of all malignant tumors.The incidence of lung cancer among the world's malignant tumors is the highest in 2018.Lung cancer seriously affects human life and health.Nowadays,the diagnostic methods of non-small cell lung cancer,such as X-ray and CT,are gradually increasing,but there are still large deficiencies in the early diagnosis of lung cancer.Many lung cancer patients are already in the advanced stage once they are diagnosed by lung cancer.Screening effective biomarkers for lung cancer is essential for the early diagnosis of lung cancer and for predicting the prognosis of patients.Even these abnormal expression markers can be used as targets for research and development of new drugs.The PITX gene family is involved in the early development of mammalian embryos and contains three homologous genes PITX1,PITX2,and PITX3.In cancers,the PITX gene family is abnormally expressed.For example,the abnormal expression of PITX1 is associated with esophageal squamous cell carcinoma,cutaneous malignant melanoma,hepatocellular carcinoma and lung cancer.PITX2 is associated with cancers such as breast cancer,colon cancer,and prostate cancer.Abnormal expression of PITX3 is used as an indicator to predict recurrence in patients with prostate cancer.Several studies have reported the relationship between DNA methylation and survival time of the PITX gene family.Although PITX1 has been reported in lung cancer,the relationship between PITX1 expression and overall survival in non-small cell lung cancer is unclear.The relationship between PITX1 methylation level and overall survival is still unclear.Methods: We used the TCGA-LUNG database to analyze the differential expression of the PITX gene family in lung cancer.The prognosis of patients who have lung adenocarcinoma and lung squamous cell carcinoma was analyzed by UCSC Xena Browser.In addition,we analyzed the different expression of PITX1 in different subtypes of lung adenocarcinoma and analyzed the prognosis of patients with different subtypes.The relationship between the methylation level of PITX1 and the prognosis of patients was analyzed.Finally,GSEA analyzed the pathways PITX1 enrich in.Results: 1.PITX gene family expression was up-regulated in non-small cell lung cancer compared with normal lung tissue2.Higher PITX1 expression was remarkably associated with poor overall-survival over 2 years(P=0.004754),5 years(P=0.01469)and 10 years(P=0.02935)in patients with lung adenocarcinoma,not in patients with lung squamous cell carcinoma.3.PITX1 expression is related to sexes,TNM stage ?-? stage,T stage 2-4 stage and regional lymph node status.4.PITX1 has the lowest expression in bronchioid subtype,meanwhile PITX1 expression was highest in squamoid and magnoid subtype.5.High DNA methylation of PITX1 indicates poor overall-survival in lung adenocarcinoma patients.6.GSEA showed that inflammatory response,TNF? signaling through NF?B,TGF? signaling,IL6-JAK-STAT3 signaling and interferon Gamma response were significantly enriched in high PITX1 expression.Conclusion:1.PITX1 is a potential biomarker for early detection and prognosis prediction of lung adenocarcinoma patients.2.The expression of PITX1 is associated with the inflammatory and immune response pathways.