Background/Aim: Microtubule-associated scaffold protein 1 (MTUS1) acts as tumor suppressor in several cancer types. This study assessed the relationship between clinicopathological characteristics and expression of microRNA candidates based on MTUS1 expression in gallbladder cancer (GBC). Materials and Methods: MTUS1 expression was evaluated by immunohistochemical staining of tissue microarrays from 109 cases of GBC. The association of MTUS1 expression with clinicopathological factors was explored. Two microRNA candidates (miR-19a-3p, and miR-19b-3p), which were identified by a literature review and computational analysis, were assessed in GBC tissue samples by quantitative real-time polymerase chain reaction. Results: Low MTUS1 expression in GBC was associated with high histological grade, perineural invasion, lymphovascular invasion, high T-stage, advanced TNM stage, poorer disease-free survival, and poorer cancer-specific survival. No statistical association between MTUS1 expression and expression of microRNA candidates was observed. Conclusion: MTUS1 may act as tumor suppressor and might be a potential biomarker for predicting prognosis in GBC. Although gallbladder cancer (GBC) is rare, it is the most common malignant tumor of the biliary tract (1-4). No specific symptoms or reliable diagnostic markers are established for GBC. In addition, GBC is diagnosed late; moreover, systemic chemotherapy and radiation therapy do not produce significant improvement in survival or quality of life for patients with GBC (1-3). Thus, patients with GBC do not have a favorable clinical outcome (1-3). Therefore, it is essential to evaluate new biomarkers for predicting the prognosis of patients with GBC. Microtubule-associated scaffold protein 1 (MTUS1), also known as angiotensin II receptor-interacting protein (ATIP), is located on chromosome 8p22 and contains 17 exons (5, 6). MTUS1 acts as a tumor-suppressor gene, exhibiting low expression in a variety of malignancies, including breast, colorectal, head and neck, ovary, stomach, salivary gland, and urinary bladder cancer (7-18). MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression by binding target mRNA at the post-transcriptional level. As miRNA pairing targets mRNAs in an imperfect manner, a single miRNA can target multiple genes; and one gene may be affected by multiple miRNAs (1, 19, 20). Recently, Ge et al. demonstrated that miR-19a and miR-19b co-regulate MTUS1 in lung cancer (14). Kara et al. reported decreased MTUS1 expression and elevated miR-183-5p expression in advanced stages of breast cancer (10). Additionally, several miRNAs including miR-135b-5p, miR-373-3p, miR-183-5p, miR-142-5p, miR-200c-3p, and miR-19a-3p, may play important roles in colorectal carcinoma through MTUS1 (21). The role of MTUS1 as a tumor suppressor has been reported, however, the expression of MTUS1 and its clinicopathological significance in GBC has not yet been evaluated. Thus, this study aimed to assess the clinicopathological parameters in association with MTUS1 expr...

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AimsCD47 is upregulated on the surface of various tumour cells, and it is known to inhibit the phagocytosis of tumour cells by macrophages. Immunotherapy that targets CD47 has demonstrated success in preclinical trials and is now under clinical investigation for both solid and haematological malignancies. However, data regarding CD47 expression in hepatocellular carcinoma (HCC) tissue and its correlation with clinical outcomes in patients with HCC remain limited. Here, we investigated the clinicopathological features associated with CD47 expression in HCC.MethodsCD47 expression was evaluated by immunohistochemistry in tissue microarray sections containing 166 HCC tissues. CD47 expression was considered positive if 10% or more tumour cells were stained.ResultsCD47 expression was observed in 36 (21.7%) of 166 HCC tissues and was significantly associated with frequent large vessel invasion, advanced American Joint Committee on Cancer stage and higher Ki-67 proliferation index. In the survival analyses, CD47 expression was not associated with recurrence-free survival or overall survival in total patients with HCC. However, in patients who received surgical resection without any adjuvant treatment, CD47 expression was associated with shorter recurrence-free survival.ConclusionsCD47 expression was significantly associated with adverse pathological features and poor clinical outcomes in patients with HCC who did not receive adjuvant treatment.

PurposeMesenchymal epithelial transition (MET) is a proto-oncogene that encodes a heterodimeric transmembrane receptor tyrosine kinase for the hepatocyte growth factor. Aberrant MET signaling has been described in several solid tumors—especially non-small cell lung cancer— and is associated with tumor progression and adverse prognosis. As MET is a potential therapeutic target, information regarding its prevalence and clinicopathological relevance is crucial.Materials and MethodsWe investigated MET expression and gene amplification in 113 gallbladder cancers using tissue microarray. Immunohistochemistry was used to evaluate MET overexpression, and silver/fluorescence in situ hybridization (ISH) was used to assess gene copy number.ResultsMET overexpression was found in 37 cases of gallbladder carcinoma (39.8%), and gene amplification was present in 17 cases (18.3%). MET protein expression did not correlate with MET amplification. MET amplification was significantly associated with aggressive clinicopathological features, including high histological grade, advanced pT category, lymph node metastasis, and advanced American Joint Committee on Cancer stage. There was no significant correlation between any clinicopathological factors and MET overexpression. No difference in survival was found with respect to MET overexpression and amplification status.ConclusionOur data suggested that MET might be a potential therapeutic target for targeted therapy in gallbladder cancer, because <i>MET</i> amplification was found in a subset of tumors associated with adverse prognostic factors. Detection of <i>MET</i> amplification by ISH might be a useful predictive biomarker test for anti-MET therapy.

Microtubule-associated tumor suppressor 1 (MTUS1) is thought to be downregulated in arious human cancers, which suggests its role as a tumor suppressor. This study investigated the clinicopathological significance of MTUS1 expression in lung adenocarcinoma. Tissue microarray blocks consisting of 161 cases were constructed, and immunohistochemical staining was used to assess MTUS1 expression. Correlations of MTUS1 expression and clinicopathological parameters were analyzed. In addition, we used public databases and performed bioinformatics analysis. Low level of MTUS1 was significantly associated with higher clinical stage (p = 0.006), higher tumor stage (p = 0.044), lymph node metastasis (p = 0.01), worse histologic grade (p = 0.007), lymphovascular invasion (p = 0.014), and higher Ki-67 proliferation index (p < 0.001). Patients with low MTUS1 expression also showed shorter disease-free survival (p = 0.002) and cancer-specific survival (p = 0.006). Analysis of data from the Cancer Genome Atlas confirmed that the mRNA expression of MTUS1 in lung adenocarcinoma was significantly lower than that of normal lung tissue (p = 0.02), and patients with decreased MTUS1 expression showed significantly shorter overall survival (p = 0.008). These results suggest that MTUS1 may be a potential biomarker for predicting clinical outcomes in lung adenocarcinoma patients.