Study On Mechanism Of Cell Cycle - Associated Protein ZYG11A Promoting Malignant Progression Of Lung Adenocarcinoma

Part 1:ZYG11A was identified as a potential novel oncogene in non-small cell Lung cancer.Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide, with a 5-year survival rate of less than 15% in most countries, even if patients accept the standard therapies. In recent years, with the development of abundant open data resources. It is now possible for researchers to identify cancer-related genes much more conveniently and effectively. Through an analysis of the TCGA database, we identified a set of 7 novel lung cancer-related candidate genes that were differentially expressed between cancerous and normal tissues. Our previous microarray analysis yielded similar results (with the fold change of 2.46 between lung cancer tissues and normal tissues). Through a careful review of the literature, we found a number of these genes had been investigated previously. However, among the as yet unknown genes, ZYG11A showed a much higher fold-change between cancer and paired normal tissues (with an average 5.88 fold-change in the TCGA-LUNG dataset, p<0.00001). We therefore chose ZYG11A as the candidate gene for further investigation.Part 2:The oncological phenotype and mechanism exploring of ZYG11A in non-small cell Lung cancer.Our study suggests that ZYG11A is hyper-expressed in NSCLC and correlates with larger primary tumor size and more advanced TNM stage. ZYG11A can promote proliferation, migration, and invasion of NSCLC cells in vitro and accelerate tumor growth in vivo. In addition, ZYG11A depletion suppresses cell cycle progression by inhibiting CCNE1 expression, and ectopic expression of CCNE1 in H1299 cells with ZYG11A knockdown greatly increased their proliferation and migration abilities. This suggests ZYG11A is an oncogene in NSCLC and may represent a novel diagnostic and therapeutic target for treatment of NSCLC.Part 3:The prognosis value of ZYG11A in non-small cell Lung cancer.ZYG11A protein was increased in tumor tissues, expression of ZYG11A protein was higher in tumor tissues compared with their relative normal tissues (in 67/82 tissues examined). High ZYG11A expression (as determined by a cut-off score of 140) was detected in 47 (56.6%) of the 83 lung cancer tissues, compared with only 12 (13.5%) of 89 adjacent normal tissue samples. There was a positive correlation between ZYG11A protein expression and patients’TNM stage. Multivariate analyses indicated that increased expression of ZYG11A was associated with poorer overall survival rate (HR:2.489,95%CI:1.248-4.963, p=0.010). Greater T stage and TNM stage were also associated with poorer prognosis(p=0.0022).