Enhanced TOP2A Protein Expression And Aneuploidy Are Associated With Poor Prognosis In Patients With NSCLC

Objective:In this study,TOP2 A protein expression and gene status were detected in NSCLC,and the relationship between TOP2 A protein expression and gene status and clinicopathological features and prognosis of NSCLC was analyzed to explore: the role of TOP2 A protein expression and gene status changes in the development and progression of NSCLC;the relationship between TOP2 A protein expression and chromosome 17 aneuploidy.Methods:Clinical data and lung cancer tissues from 244 patients with non-small cell lung cancer and 55 cases of paraneoplastic tissues were collected to make tissue microarrays.The pathological classification and clinical staging of patients were redetermined,and the expression of TOP2 A protein and genes were detected by immunohistochemical staining(IHC)and fluorescence in situ hybridization(FISH)techniques,respectively.Clinicopathological data were examined by Pearson’s chi-square test.Survival analysis was performed by Kaplan-Meier and multivariate Cox regression equation analysis.The consistency of aneuploidy with TOP2 A protein expression was analyzed by Kappa concordance test.Results1.IHC results showed that the high expression rate of TOP2 A protein in NSCLC tissues was 29.9%(73/244).Compared with the high expression rate of TOP2 A protein in adjacent tissues of 16%(9/55),the expression rate of TOP2 A protein in NSCLC tissues was increased(P < 0.05).Patients with high expression of TOP2 A had poor prognosis(P < 0.001).In addition,TOP2 A protein has different distribution patterns in different histological types of lung cancer.In LUSC,TOP2 A protein positive tumor cells were more likely to cluster at the edge of the nests,while in LUAD,TOP2 A protein positive tumor cells were more likely to be scattered.The difference between the two distribution patterns was statistically significant(P < 0.001).In both squamous cell carcinoma and adenocarcinoma,patients with high expression of TOP2 A protein at the edge of the carcinoma nest had a poor prognosis(P <0.001).2.FISH results showed that the amplification rate of TOP2 A gene was 1.2%(3/244),deletion rate was 3.3%(8/244),and aneuploid rate was 31.6%(77/244).Genetic abnormalities(amplified or deleted)were not associated with prognosis(P > 0.05).TOP2 A gene abnormalities were more likely to occur in non-smokers(P < 0.01).Kappa consistency test showed that the expression of TOP2 A gene was inconsistent with that of TOP2 A protein,suggesting there are other regulatory pathways of TOP2 A protein(K < 0).3.Overall survival and progression-free survival were shortened in NSCLC patients with chromosome 17 aneuploidy(P < 0.001).Kappa test results showed moderate consistency between TOP2 A protein and chromosome 17 aneuploidy,suggesting that the occurrence of aneuploidy on chromosome 17 May be related to the high expression of TOP2 A protein(K=0.307).4.The high expression of TOP2 A protein at the edge of the tumor and the aneuploidy of chromosome 17 were independent risk factors for NSCLC patients(P < 0.001),suggesting that the edge distribution pattern of TOP2 A protein and aneuploidy of chromosome 17 could be used as indicators of the risk of death in NSCLC patients.Conclusion1.The high expression of TOP2 A protein was consistent with chromosome 17 aneuploidy,and both of them promoted the development of NSCLC.2.High expression of chromosome 17 aneuploidy and TOP2 A protein in tumor parenchymal margin can predict poor prognosis of NSCLC patients.