MiR-139-5p inhibits the proliferation of gastric cancer cells by targeting Regulation of Nuclear Pre-mRNA Domain Containing 1B.

Regulation of Nuclear Pre-mRNA Domain Containing 1B (RPRD1B) has been of great interest in the field of oncology in recent years. The relationship between miRNAs and RPRD1B in gastric cancer (GC) has not been adequately reported. This study was designed to screen RPRD1B-targeted miRNAs and investigate its regulatory mechanism in GC cells. Quantitative RT-PCR and in situ hybridization were used to detect miRNA expression in GC tissues. Colony formation, EdU cell proliferation assay, and flow cytometry were used to analyze the cell cycle. Database-assisted gene expression analysis revealed that RPRD1B was targeted and regulated by miRNA-139-5p in GC. miRNA-139-5p expression was higher in GC tissue than in normal tissues and significantly correlated with tumor size, pathological stage, and disease-free survival of GC (p < 0.05). MiRNA-139-5p regulates GC cell proliferation and affects the transition from G1 to S phase. It binds explicitly to the 2013-2019 sites of the 3'UTR of RPRD1B and negatively regulates RPRD1B expression. We demonstrated that the ability of miR-139-5p to regulate GC cell proliferation depends on RPRD1B. This process is accompanied by changes in Cyclin D1 protein expression. We established a miR-139-5p/RPRD1B/tumor proliferation axis in GC, which may serve as novel biomarkers and drug targets for GC.

Clinicopathologic features and prognostic analysis of 240 patients with gastric neuroendocrine neoplasms / 中华胃肠外科杂志

Objective@#To investigate clinicopathological features and prognostic factors of gastric neuroendocrine tumors (G-NEN).@*Methods@#Clinical and pathological data of patients with G-NEN diagnosed by pathological examination in Chinese PLA General Hospital from January 2000 to June 2018 were retrospectively analyzed in this case-control study. Patients with complicated visceral lesions, other visceral primary tumors, mental disorders and incomplete clinicopathological data were excluded. Finally, 240 hospitalized patients who met the inclusion criteria were enrolled. Physical examination information, tumor characteristics and pathological characteristics of patients were summarized. The Cox regression models were used to analyze the risk factors affecting G-NEN and the survival conditions were described by Kaplan-Meier survival curves and log-rank test.@*Results@#In 240 patients with G-NEN, the mean age was (60.3±10.1) years; 181 were male (75.4%) and 59 females (24.6%); mean tumor diameter was (4.2±2.8) cm; 51 cases (21.2%) were neuroendocrine tumor (NET), 139 cases (57.9%) neuroendocrine carcinoma (NEC), 50 cases (20.8%) mixed neuroendocrine carcinoma (MANEC); 28 cases (11.7%) were G1 low grades, 34 cases (14.2%) G2 medium grades, and 178 cases (74.2%) G3 high grades; tumor infiltration depth T1 to T4 were 44 cases (18.3%), 27 cases (11.2%), 60 cases (25.0%) and 109 cases (45.4%) respectively; 163 cases (67.9%) developed lymphatic metastasis and 46 patients (19.2%) distant metastasis; tumor stage from stage I to stage IV were 55 cases (22.9%), 42 cases (17.5%), 94 cases (39.2%) and 53 cases (22.1%) respectively. Of the 240 G-NEN patients, 223 cases (92.9%) were followed up. The median survival time of the patients was 39.2 (95% CI: 29.1 to 47.5) months. Univariate survival analysis showed that age ≥ 60 years, tumor diameter ≥ 4.2 cm, tumor grade G3, lymphatic metastasis, distant metastasis, and tumor stage III-IV were risk factors for G-NEN patients. Multivariate survival analysis revealed that lymphatic metastasis (HR=1.783, 95%CI: 1.007-3.155, P=0.047) and distant metastasis (HR=2.288, 95% CI: 1.307-4.008, P=0.004) were independent risk factors of the prognosis. Further analysis of the G3 subgroup of G-NEN showed that the 5-year survival rate of NET-G3 was 76.19%, which was significantly higher than that of NEC-G3 and MANEC-G3 (15.60% and 24.73%, P=0.012).@*Conclusions@#Most G-NEN patients are in advanced stage at diagnosis. Lymphatic metastasis and distant metastasis indicate poor prognosis. The prognosis of high proliferation NET-G3 patients is better as compared to those of NEC-G3 and MANEC-G3. This classification is worth further attention.

Clinicopathologic features and prognostic analysis of 104 patients with gastric neuroendocrine neoplasms / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features and prognostic factors of gastric neuroendocrine neoplasms(gNENs).</p><p><b>METHODS</b>Clinicopathologic data of 104 patients with gastric neuroendocrine neoplasms admitted in Chinese PLA General Hospital between January 2000 and December 2014 were analyzed retrospectively. Tumor proliferation activity classification (G1, G2 and G3) and TNM staging were observed. The clinicopathologic features of the whole group were collected and the univariate and multivariate analysis were determined by Log-rank and Cox proportional hazard model to detect the prognosis-determining features.</p><p><b>RESULTS</b>Of all the patients, 66 cases(63.5%) were neuroendocrine carcinoma, 25 cases(24.0%) were mixed adenoendocrine carcinoma and 12 cases (11.5%) were neuroendocrine tumor. For G grades, 92 cases (88.5%) were G3 grade, 8 cases(7.7%) were G2 grade and 4 cases (3.8%) were G1 grade. TNM staging results showed that stageI( was found in 6 cases (5.8%), stageII(A in 6 cases (5.8%), stageII(B in 9 cases (8.7%), stage III(A in 8 cases (7.7%), stage III(B in 55 cases (52.9%) and stageIIII( in 20 cases (19.2%). For T stage, 7 cases (6.7%) were T1, 12 cases (11.5%) were T2, 24 cases (23.1%) were T3, and 61 cases (58.7%) were T4. Lymph node metastasis occurred in 73 cases (70.2%) and distant metastasis occurred in 20 cases(19.2%). Eighty-six patients were followed up for 6 to 186 months. The median survival was 33.0 months(95% CI: 28.3 to 36.6), and 1-, 3-, and 5-year survival rates were 80%, 49% and 31%. Clinicopathologic features which were considered statistically significant on univariate analysis were selected to Cox proportional hazard model. Univariate analysis showed that risk factors of reducing survival rate included tumor size, pathological type, proliferation activity grades, and depth of invasion (all P<0.05), as well as chromogranin A expression, tumor staging, lymph node metastasis and distant metastasis(all P<0.01). The multivariate analysis showed that the stage of gNEN was the independent risk factor of the prognosis (RR=14.213, 95% CI: 1.316 to 153.524, P=0.029).</p><p><b>CONCLUSION</b>Late staging is the main clinical feature and a prognostic factor for gNENs.</p>