MCM6促进食管癌细胞增殖进而导致预后不良（英文）_李德茂.pdf

南 开 大 学 学 报（自然科学版）Acta Scientiarum Naturalium Universitatis NankaiensisVol.561Feb.2023第56卷第1期2023年2月Article ID:0465-7942(2023)01-0046-08MCM6 Contributes to the Proliferation of Esophageal CarcinomaCells and Predicts Poor PrognosisLi Demao1,Sun Huijie2,Meng Linglei3,Li Deshang4(1.Department of Thoracic Surgery,Xingtai Peoples Hospital,Xingtai 054000,China.2.Department of Pharmacy,Xingtai Medical College,Xingtai 054000,China;3.Department of CT/MR,Xingtai Peoples Hospital,Xingtai 054000,China;4.Department of Laboratory,Xingtai Peoples Hospital,Xingtai 054000,China)Abstract:Esophageal carcinoma(ESCC)is a common type of fatal cancer with high mortality.The purposeis to identify key genes and determine the potential mechanisms involved in the development of esophagealcarcinoma based on bioinformatics analysis.Chromosome maintenance 6 complex(MCM6)has been identifiedto be up-regulated in a variety of malignancies.However,its effects on esophageal carcinoma remain unclear.Using the GEPIA database,it was investigated how MCM6 expression varied between healthy and cancerousesophagus tissues.And the result that ESCC with high MCM6 gene expression was found.Then immuno-histochemistry(IHC)assay was performed to detect MCM6 expression in both healthy and malignant esophagealtissues,and the result showed high MCM6 protein expression in ESCC.The 2 analysis to explore thecorrelation between clinic-pathological features and protein expression and the tumor size of esophageal cancerwas substantially associated with MCM6 expression in 78 patients in our hospital.By performing a colonyformation assay,the promoting effect of MCM6 on the proliferation of esophageal cancer cells was identified.Tumor growth assay confirmed the promoting role of MCM6 in the progression of esophageal cancer in vivo.The correlation between MCM6 and PCNA was detected by database and immunohistochemistry,and we foundthat MCM6 was positively correlated with PCNA expression.Further,it was speculated that MCM6 mightpromote the proliferation of esophageal cancer cells by mediating PNCA expression.In conclusion,MCM6 mightbecome a new target for the treatment of esophageal carcinoma.Keywords:MCM6;PCNA;esophageal carcinoma;proliferation;biomarkerCLC number:R735.7Document code:A0IntroductionOne of the deadliest and most prevalent cancer types,esophageal cancer(ESCC),has a highmorbidity and mortality rate and is a public health issue1-3.In 2020,there were 604 100 new cases and544 076 deaths of esophageal cancer worldwide,accounting for 3.1%and 5.5%of the total cases anddeaths,respectively.The standardized morbidity and mortality were 6.3/100 000 and 5.6/100 000,respectively,and the cumulative risk of morbidity and mortality between 0 and 74 years was 0.78%and0.68%,respectively4.Factors affecting esophageal cancer mainly included age,sex,stage,and body massindex5-7.Patients are typically diagnosed at an advanced stage of the illness,so past the point at whichtreatment is likely to be effective.Even with the help of surgery and other adjunctive therapies suchaschemoradiotherapy,radiotherapy and targeted therapy,20%-25%of esophageal cancer patients survivefor more than five years8-9.Although the occurrence of esophageal cancer is related to many genes,esophageal cancer is challenging to detect early,treat,and assess the prognosis for10.Therefore,findingReceived date:2022-02-08Foundation item:Supported by Xingtais key research and development program self-found projectBiography:Li Demao(1985-),male,native place:Hebei Xingtai,attending doctor.Corresponding author:Li Deshang(1989-),male,nativeplace:Hebai Xingtai,chief examiner,direction of re-search:clinical laboratory diagnosis.E-mail:李德茂等：MCM6促进食管癌细胞增殖进而导致预后不良第1期李德茂等：MCM6促进食管癌细胞增殖进而导致预后不良 47 new therapeutic targets is crucial for esophageal cancers early detection and prognosis.Maintenance of complex components(MCMs)has been identified to play an important role ineukaryotic genome replication11.During late M-early G1 of the cell cycle,the MCM2-7 complex bindsto the origin of DNA replication12.In eukaryotic cells,this complex acts as a replication helicase,whichis required for the initiation and extension of DNA replication13-14.MCM6 is a member of the MCMprotein complex.Several studies have confirmed the abnormal expression of MCM6 in various types ofcancer,such as meningioma,non-small cell lung cancer,chondrosarcoma,endometrioid intrauterineadenocarcinoma,and colorectal cancer15-19.Elevated levels of serum MCM6 have also been reported inhepatocellular carcinoma20-21.In addition,high MCM6 expression was associated with a higher risk ofmeningioma recurrence,suggesting that MCM6 is a promising prognostic marker15.However,its rolein esophageal cancer is still unclear.1Materialsandmethods1.1 Gene expression GEPIAanalysisThe latest development of the online software GEPIA(http:/gepia.cancer- basedon genes expression(GTEx)data and the cancer genome atlas(TCGA)RNA sequence of the program,including 9 736 cancer samples and