Expression Profile and Prognostic Values of IRX Family Members in Lung Adenocarcinoma

Background: The potential role of the iroquois homeobox (IRX) genes in tumorigenesis is a subject of interest, yet their specific involvement in lung adenocarcinoma (LUAD) has not been extensively examined. Objective: This research endeavored to explore the impact of the IRX genes on the onset and progression of LUAD. Methods: Utilizing data from The Cancer Genome Atlas (TCGA), samples of LUAD were selected for analysis. The influence of the IRX genes was scrutinized through various tools, including Kaplan-Meier Plotter, cBioPortal, and the R programming language (version 3.6.3), with gene expression levels being confirmed in cellular models via quantitative real-time polymerase chain reaction (qRT-PCR). Results: It was observed that the levels of IRX1/2/3/6 were notably diminished in LUAD tissues when juxtaposed with healthy lung tissue. Conversely, the expression of IRX4 was found to be elevated in LUAD. Correlations were identified between IRX gene expression and several clinical parameters such as T stage, smoking history quantified in pack-years, lymph node involvement, patient gender, initial treatment responses, and smoking status. The diminished expression of IRX2/5 emerged as a significant indicator of an unfavorable prognosis in LUAD. The study also highlighted the potential of various IRX genes as diagnostic indicators for LUAD. These genes were implicated in the facilitation of LUAD's growth and spread through a range of biological pathways, encompassing the Ras signaling and more. Additionally, a pronounced link was discovered between the infiltration of immune cells and the expression patterns of the IRX genes. IRX genes were abnormally expressed in LUAD cell lines. Conclusion: IRX gene family could serve not only as indicators of LUAD prognosis but also as therapeutic targets for LUAD.