Identification of MCM4 as an independent prognostic factor and correlate with immune infiltration in Lung Adenocarcinoma through bioinformatics analysis

Abstract

Background: Lung cancer is the most common malignant tumor with the highest mortality all over the world. Among it, Lung Adenocarcinoma owns the highest proportion of pathological classification.Yet, the fuction of MCM4 in the occurrence of Lung Adenocarcinoma is still unknown.In this research, we attempted to disscuss the potential role of MCM4 in LUAD through bioinformatics analysis and hoped to provide a new idea for clinical treatment.Methods: The data of Lung Adenocarcinoma in TCGA and GEO were downloaded.The correlation between MCM4 and immune infiltration were performed by R software packages .Enrichment analysis were underwent to analyze the functions of MCM4. Univariate and multivariate Cox regression analysis were utilized to determine whether MCM4 could be act as an independent prognostic factor for Lung Adenocarcinoma.Lastly,the expression of MCM4 was validated in clinical tissues by immunohistochemistry (IHC), real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and western blotting (WB).Results: The expression of MCM4 was up-regulated in 13 tumors and was significantly correlated with age, gender, stage, T, N and smoke history. Furthermore, the Kaplan-Meier survival curves pointed that LUAD samples with lower MCM4 expression had longer Overall survival (OS) and the Disease-free survival (DFS) in 4 datasets. Univariate Cox regression analysis showed that the p value of MCM4 expression was less than 0.05(P＜0.05) and it appeared in the results of multivariate Cox regression analysis(HR≥1), which indicated that MCM4 can be used as an independent prognostic factor for LUAD.Enrichment Analysis suggested that MCM4 was correlated with the multiple biological functions and involved in vital pathways in GO and KEGG. Furthermore, the MCM4 expression was correlated with immune cells infiltration.Finally,the experimental results were consistent with the bioinformatic analysis.Conclusion: MCM4 might serve as a prognostic biomarker and correlate with immune infiltration in LUAD.