Alternatively Expressed Transcripts Analysis of Non-Small Cell Lung Cancer Cells under Different Hypoxic Microenvironment

Abstract

Globally, non-small cell lung cancer (NSCLC) is the most fatal form of malignancy. Numerous studies have shown that people living at high altitudes are at a higher risk for cancer. Hypoxia is one of the most important features in high altitude area. Compared with normal cells, cancer cells are more adapted to hypoxia atmosphere. However, at high altitudes, hypoxic conditions are also accompanied by other altered environmental conditions. To identify the single influence of hypoxia, we performed second-generation sequencing to identify gene expression changes triggered by the different oxygen concentrations. We identified 782 genes in A549 cells and 1122 genes in H520 cells that showed altered expression by the combined analysis in 5% oxygen concentration group and 1% oxygen concentration group control group. We further analyzed these targets and found 113 genes altered in both cell lines. Interestingly, we found KxD1 was the only one in both top 10 lists. Further analysis revealed KxD1 to be significantly elevated in NSCLC patients and negatively correlated with prognosis in stage I and II NSCLC patients. Moreover, this correlation reversed in stage III patients. Additionally, compared with patients who only received clean margin operation or chemotherapy, patients who received radiotherapy also showed opposite result. Thus, KxD1 may be a promising target for the treatment of NSCLC in high-altitude areas.