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Purpose: The aim of this study was to elucidate the prognostic value of proenkephalin (PENK) in gastrointestinal stromal tumors (GISTs). Patients and methods: We collected data on 268 eligible postoperative patients diagnosed with GIST between January 1, 2002, and December 31, 2011. PENK expression was detected in GIST tissues classified using the United States National Institutes of Health (NIH) risk classification system. The associations between high PENK expression and the clinicopathological characteristics were assessed. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan–Meier analysis, and the log-rank test was used to compare the differences between groups. Univariate and multivariate Cox regression analyses were conducted to assess the prognostic value of PENK in GIST patients. Results: High PENK expression was more common in the low- and intermediate-risk GIST groups compared with the high-risk group (P<0.05). Additionally, PENK expression was associated with tumor size, mitosis count per 50 high-power fields, and tumor rupture (P<0.05). Kaplan–Meier analysis revealed that high PENK expression was associated with superior OS and RFS, while low PENK expression was associated with worse OS and RFS. Furthermore, PENK was shown to be an independent predictor of OS and RFS in the overall population (for OS, hazard ratio [HR], 1.596, 95% confidence interval [CI], 1.006–2.914, P<0.001; for RFS, HR, 1.910, 95% CI, 0.977–3.089, P<0.001). Conclusion: PENK expression in GIST is closely associated with NIH risk grade and prognosis, indicating that PENK may act as a tumor suppressor and may serve as a new biomarker for predicting prognosis in postoperative GIST patients. [ABSTRACT FROM AUTHOR]

Background. In recent studies, aberrant expression of various microRNAs (miRNAs) is reported to be associated with gastric cancer metastasis. Method. Overexpression construct and inhibitor of hsa-miR-376c-3p were expressed in human gastric adenocarcinoma cell line SGC-7901. The expression level of tumor related genes was detected by qPCR, western blot, and immunostaining. Cell apoptosis was determined by flow cytometry. Xenograft of SGC-7901 cells was used to elucidate the function of hsa-miR-376c-3p in gastric tumor growth in vivo. Result. Expression of hsa-miR-376c-3p was detected in SGC-7901 cells. Downregulation of hsa-miR-376c-3p increased the expression level of BCL-2 and decreased the expression of smad4 and BAD. On the contrary, overexpression of hsa-miR-376c-3p increased the expression of BAD and smad4, while it led to the decreasing expression level of BCL-2. Overexpression of hsa-miR-376c-3p also promoted cell apoptosis in vitro and inhibited gastric tumor growth in vivo. Furthermore, the expression of BCL-2 was higher and expression of smad4 and BAD was lower in tumor tissue than the tissue adjacent to tumor from gastric cancer patients. Conclusion. This study demonstrated that hsa-miR-376c-3p plays an important role in the inhibition of gastric tumor growth and tumor related gene expression both in vitro and in vivo. [ABSTRACT FROM AUTHOR]