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Ubiquitin-specific proteases (USPs) play an important role in fundamental cellular processes. Among these, USP10 is known for its association with tumor development and progression of multiple cancers. We aimed to investigate the clinical significance of USP10 expression in colorectal cancer and examined the potential link between USP10 and p14ARF in patients with colorectal cancer. USP10 and p14ARF protein expression was assessed via immunohistochemistry (IHC) on a tissue microarray from 280 colorectal cancer cases. IHC scores were evaluated by digital image analysis and compared with patients' outcomes. In addition, we examined DNA hypermethylation in colorectal cancer cell lines and tissues, which were matched with adjacent normal colon samples. USP10 expression was lost (USP10loss) in 18.6% of samples (52/280 cases), which was linked to lymphovascular invasion (p = 0.019) and distant metastases (p < 0.001). Similarly, loss of p14ARF expression (p14ARFloss) was associated with more advanced tumors. USP10 expression correlated positively with p14ARF expression (r = 0.617, p < 0.001). USP10loss, p14ARFloss, and dual loss of USP10 and p14ARF were significantly associated with shorter disease-free survival and overall survival in comparison to USP10intact, p14ARFintact, and dual loss of USP10 and p14ARF, respectively. Multivariate analysis revealed that USP10loss (p = 0.030) and dual loss of USP10 and p14ARF (p = 0.014) are independent prognostic factors for poor disease-free survival in colorectal cancer patients. Furthermore, aberrant hypermethylation of the USP10 promoter region was found in colorectal cancer cell lines and tissues. The present results suggest that USP10loss is a potential prognostic marker for colorectal cancer.

The clinicopathological and prognostic significance of olfactomedin-4 (OLFM4) expression has not yet been elucidated in extrahepatic bile duct carcinomas (EBDCs). Immunohistochemical analysis of OLFM4 expression in 31 normal biliary epithelia, 33 biliary intraepithelial neoplasias (BilINs), and 180 surgically resected EBDCs (54 perihilar and 126 distal) was performed and was used to analyze clinicopathological variables including patient survival. The expression of OLFM4 showed a progressive increase from normal biliary epithelia (0.2 ± 0.4) to BilINs (2.8 ± 3.2) to EBDCs (4.6 ± 4.2; P0.001). OLFM4 was highly expressed in 26.1% (47/180) of the EBDC cases, and high OLFM4 levels were more frequently observed in tumors with nodular growth (P = 0.029), well differentiation (P = 0.011), and lower T-category (P = 0.025) and stage grouping (P = 0.013). Patients with EBDC having high expression of OLFM4 had better survival than those with low expression of OLFM4 (median, 43.3 vs. 29.2 months; P = 0.037). OLFM4 might play an important role in carcinogenesis and in the progression from BilINs to EBDCs. High OLFM4 expression predicted less aggressive clinical behavior in patients with EBDC.