J Korean Med Sci.  2014 Mar;29(3):351-356. 10.3346/jkms.2014.29.3.351.

Novel Combination Markers for Predicting Survival in Patients with Muscle Invasive Bladder Cancer: USP18 and DGCR2

• Kim YH
• Kim WT
• Jeong P
• Ha YS
• Kang HW
• Yun SJ
• Moon SK
• Choi YH
• Kim IY
• Kim WJ

• KMID: 1734921
• DOI: http://doi.org/10.3346/jkms.2014.29.3.351

Abstract

We performed gene expression profiling in bladder cancer patients to identify cancer-specific survival-related genes in muscle invasive bladder cancer (MIBC) patients. Sixty-two patients with MIBC were selected as the original cohort and another 118 MIBC patients were chosen as a validation cohort. The expression of USP18, DGCR2, and ZNF699 genes were measured and we analyzed the association between gene signatures and survival. USP18 and DGCR2, were significantly correlated to cancer-specific death (P=0.020, P=0.007, respectively). Cancer-specific survival in the low USP18 or DGCR2 expression group was significantly longer than the high expression group (P=0.018, P=0.006, respectively). In multivariate Cox regression analysis, a combination of USP18 and DGCR2 mRNA expression levels were significant risk factors for cancer-specific death (HR, 2.106; CI, 1.043-4.254, P=0.038). Overall survival and cancer-specific survival rates in the low-combination group were significantly longer than those in the high-expression group (P=0.001, both). In conclusion, decreased expressions of USP18 and DGCR2 were significantly associated with longer cancer-specific survival, and also the combination of two genes was correlated to a longer survival for MIBC patients. Thus, the combination of USP18 and DGCR2 expression was shown to be a reliable prognostic marker for cancer-specific survival in MIBC.

Keyword

Urinary Bladder Neoplasms; USP18 Protein, Human; DGCR2; Survival; Gene Expression Profiling

MeSH Terms

Adult
Aged
Aged, 80 and over
Biological Markers/metabolism
Carrier Proteins/genetics/metabolism
Endopeptidases/genetics/*metabolism
Female
Gene Expression Profiling
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Muscle Neoplasms/*secondary
Neoplasm Invasiveness
Neoplasm Staging
Platelet Glycoprotein GPIb-IX Complex/genetics/*metabolism
Predictive Value of Tests
ROC Curve
Regression Analysis
Risk Factors
Urinary Bladder Neoplasms/*diagnosis/metabolism/*mortality/pathology
Biological Markers
Carrier Proteins
Platelet Glycoprotein GPIb-IX Complex
Endopeptidases

Figure

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  Fig. 1 Kaplan-Meier curve for prediction of cancer specific survival by USP18 expression (A), DGCR2 expression (B), and combined expression (C).

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  Fig. 2 Kaplan-Meier estimate curves predict overall survival according to the expression of USP18 (A), DGCR2 (B), and combined expression (C).

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