title: MCM10 overexpression implicates adverse prognosis in urothelial carcinoma.
abstract: Urothelial carcinoma (UC) occurs in the upper urinary tract (UTUC) and the urinary bladder (UBUC). The molecular pathogenesis of UC has not been fully elucidated. Through data mining of a published transcriptome of UBUC (GSE31684), we identified Minichromosome Maintenance Complex Component 2 (MCM2) and MCM10 as the two most significantly upregulated genes in UC progression among the MCM gene family, the key factors for the initiation of DNA replication. To validate the clinical significance of MCM2 and MCM10, immunohistochemistry, evaluated by H-score, was used in a pilot study of 50 UTUC and 50 UBUC samples. Only a high expression level of MCM10 predicted worse disease-specific survival (DSS) and inferior metastasis-free survival (MeFS) for both UTUC and UBUC. Correspondingly, evaluation of MCM10 mRNA expression in 36 UTUCs and 30 UBUCs showed significantly upregulated levels in high stage UC, suggesting its role in tumor progression. Evaluation of 340 UTUC and 296 UBUC tissue samples, respectively, demonstrated that high MCM10 immunoexpression was significantly associated with advanced primary tumors, nodal status, and the presence of vascular invasion in both groups of UCs. In multivariate Cox regression analyses, adjusted for standard clinicopathological features, MCM10 overexpression was independently associated with DSS (UTUC hazard ratio [HR]=2.401, P = 0.013; UBUC HR=4.323, P=0.001) and with MeFS (UTUC HR=3.294, P<0.001; UBUC HR=1.972, P=0.015). In vitro, knockdown of MCM10 gene significantly suppressed cell proliferation in both J82 and TCCSUP cells. In conclusion, MCM10 overexpression was associated with unfavorable clinicopathological characteristics and independent negative prognostic effects, justifying its potential theranostic value in UC.
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan.
authors: Wei-Ming
authors: WM
authors: Li
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chun-Nung
authors: CN
authors: Huang
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Hung-Lung
authors: HL
authors: Ke
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors: Ching-Chia
authors: CC
authors: Li
authors: Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors: Yu-Ching
authors: YC
authors: Wei
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors: Hsin-Chih
authors: HC
authors: Yeh
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Microbiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Lin-Li
authors: LL
authors: Chang
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chun-Hsiung
authors: CH
authors: Huang
authors: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors: Peir-In
authors: PI
authors: Liang
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Bi-Wen
authors: BW
authors: Yeh
authors: Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
authors: Ti-Chun
authors: TC
authors: Chan
authors: Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.|Departments of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.|National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan.|Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Chien-Feng
authors: CF
authors: Li
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.|Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors: Wen-Jeng
authors: WJ
authors: Wu
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D064111:Minichromosome Maintenance Complex Component 2 / Q000235:genetics* / Q000378:metabolism; D064110:Minichromosome Maintenance Proteins / Q000235:genetics* / Q000378:metabolism; D010865:Pilot Projects; D011379:Prognosis; D015854:Up-Regulation; D014571:Urologic Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: C489613:MCM10 protein, human; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D064110:Minichromosome Maintenance Proteins
keywords: MCM10; prognosis; transcriptome; urothelial carcinoma