MCM10 overexpression implicates adverse prognosis in urothelial carcinoma

Wei Ming Li, Chun Nung Huang, Hung Lung Ke, Ching Chia Li, Yu Ching Wei, Hsin Chih Yeh, Lin Li Chang, Chun Hsiung Huang, Peir In Liang, Bi Wen Yeh, Ti Chun Chan, Chien Feng Li, Wen Jeng Wu

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)77777-77792
Number of pages16
JournalOncotarget
Volume7
Issue number47
DOIs
StatePublished - 2016
Externally publishedYes

Keywords

  • MCM10
  • Prognosis
  • Transcriptome
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Oncology

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