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.

Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis in prostate cancer

“…Previous studies have observed MCM10 is overexpressed in different types of human cancers, such as medulloblastoma, cervical cancer, and esophageal cancer . Furthermore, Li et al demonstrated that MCM2 and MCM10 were the two most significantly upregulated genes in urothelial carcinoma progression among the MCM gene family . However, the functional roles and prognostic values of MCM10 remained largely unclear.…”

“…Previous studies show MCM10 is often dysregulated under pathological conditions . Genetic amplification and/or overexpression of MCM10 were also observed in different types of human cancers . For instance, Cheng et al found a series of replicative helicase proteins, such as MCM10, MCM2, MCM4, MCM5, and MCM6 were overexpressed in cervical cancer.…”

MCMs in Cancer: Prognostic Potential and Mechanisms

“…Moreover, MCMs may mediate DNA damage repair. Knockdown of MCM genes was reported to significantly inhibit cell proliferation [50,57,58]. Based on the biological and functional significance of MCMs, many MCM-targeted drugs have been developed.…”

MCM10 facilitates the invaded/migrated potentials of breast cancer cells via Wnt/β‐catenin signaling and is positively interlinked with poor prognosis in breast carcinoma

“…These observations raise the possibility that MCM10 might be closely associated with tumorigenesis. Several lines of evidence have shown the important roles of MCM10 in several malignant tumors . Al‐Ejeh et al also indicated that MCM10 was deregulated in triple negative breast cancer and might hold therapeutic potential in aggressive breast tumors.…”