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Expression And Function Of MCM10 In Lung Adenocarcinoma

Posted on:2020-01-01Degree:MasterType:Thesis
Country:ChinaCandidate:J Y ZhaoFull Text:PDF
GTID:2404330575957606Subject:Surgery
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ObjectiveLung cancer is one of the most common cancer in the world,however,the role of minichromosome maintenance 10(MCM10)in lung adenocarcinoma(ADC)is still unknown.The purpose of this study was to investigate the expression and function of MCM10 in lung adenocarcinoma.Methods1.Using TCGA(The Cancer Genome Atlas)database,we collected 473 lung adenocarcinoma patients' clinicopathologic data and analyzed the relationship between MCM10 mRNA expression and patients' clinicopathologic characteristics.2.In our patient cohort,MCM10 expression of gene and protein were detected by quantitative real-time PCR and immunohistochemistry,respectively.The relationship between MCM10 expression and clinicopathologic characteristics were further analyzed.3.RNAi(RNA interference)technology was used to knock down MCM10 expression in A549 cell line and was assessed by qRT-PCR and western blotting.4.After MCM10 expression was knocked down,CCK8,PI staining method,flow cytometry and transwell assays were used to detect cell proliferation,cell cycle,apoptosis and migration.Results1.TCGA database analysis resultMCM10 mRNA expression was higher in tumor tissues than normal tissues(P<0.001).Overall survival indicated that high expression group had poorer prognosis than low expression group(P=0.0212).MCM10 could be a diagnostic marker due to receiver operating characteristic(ROC)curve(P<0.0001).In univariate Cox regression model,OS was associated with pathologic stage,tumor stage,lymph node metastasis and MCM10 expression.Multivariate Cox regression model proved MCM10 was an important predictor for OS.Compared to MCM10 low expression group,high expression group was associated with age,gender,tumor stage,lymph node metastasis and pathological stage.2.Our database analysis resultIn our patient cohort,both MCM10 mRNA and protein expression were higher in tumor tissues than normal tissues(P<0.001).According to MCM10 mRNA expression,ROC curve was performed and the result revealed MCM10 could be a diagnostic marker.In the analysis of immunohistochemistry,high MCM10 expression group had shorter OS and PFS than low expression group.High MCM10 expression was associated with clinical stage,lymph node metastasis and survival status.3.MCM10 expression knockdown resultRNA interference revealed that MCM10 mRNA and protein expression were decreased in A549 cell line.4.Functional study results of MCM10Knockdown of MCM10 expression inhibits tumor cell proliferation,induces cycle arrest at G0/G1 phase,triggers apoptosis and decrease migration.Conclusions1.MCM10 expression was higher in tumor tissues than normal tissues and was an important prognostic factor.2.MCM10 could be a prognosis factor that could distinguish tumor tissues from normal tissues.3.The expression level of MCM10 is correlated with clinicopathological parameters.MCM10 may play an important role in the occurrence and development of lung adenocarcinoma.4.Knockdown of MCM10 expression inhibits tumor cell proliferation,induces cell cycle arrest at G0/G1 phase,triggers apoptosis and decrease migration.
Keywords/Search Tags:MCM10, Lung Adenocarcinoma, Proliferation, Cell Cycle, Apoptosis, Migration
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