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Growing evidence has revealed that long noncoding RNAs (lncRNAs) have an important impact on tumorigenesis and tumor progression via a mechanism involving competing endogenous RNAs (ceRNAs). However, their use in predicting the survival of a patient with hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to develop a novel lncRNA expression-based risk score system to accurately predict the survival of patients with HCC. In our study, using expression profiles downloaded from The Cancer Genome Atlas database, the differentially expressed messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs) were explored in patients with HCC and normal liver tissues, and then a ceRNA network constructed. A risk score system was established between lncRNA expression of the ceRNA network and overall survival (OS) or recurrence-free survival (RFS); it was further analyzed for associations with the clinical features of patients with HCC. In HCC, 473 differentially expressed lncRNAs, 63 differentially expressed miRNAs, and 1417 differentially expressed mRNAs were detected. The ceRNA network comprised 41 lncRNA nodes, 12 miRNA nodes, 24 mRNA nodes, and 172 edges. The lncRNA expression-based risk score system for OS was constructed based on six lncRNAs (MYLK-AS1, AL359878.1, PART1, TSPEAR-AS1, C10orf91, and LINC00501), while the risk score system for RFS was based on four lncRNAs (WARS2-IT1, AL359878.1, AL357060.1, and PART1). Univariate and multivariate Cox analyses showed the risk score systems for OS or RFS were significant independent factors adjusted for clinical factors. Receiver operating characteristic curve analysis showed the area under the curve for the risk score J Cell Biochem. 2019;120:13810-13825. wileyonlinelibrary.com/journal/jcb 13810 |

BackgroundEpstein–Barr virus (EBV) actively contributes to the pathological process of nasopharyngeal carcinoma (NPC) by enabling NPC cells to acquire various capacities required for their malignant biological actions. Our earlier works demonstrated that EBV-encoded latent membrane protein 1 (LMP1) enhanced vascular endothelial growth factor (VEGF)-mediated angiogenesis by boosting store-operated Ca2+ entry (SOCE) upon extracellular epidermal growth factor (EGF) stimulation. However, the antagonistic effects of SOCE blockage on EBV-promoted angiogenesis must be appropriately evaluated in vivo, and the global effect of EBV infection on the EGF-elicited cytosolic Ca2+ signaling, which regulates VEGF-mediated angiogenesis remains to be further clarified.Materials and methodsTwo EBV-infected NPC cell lines, CNE2-EBV and HK1-EBV, along with their parental cell lines were employed in the present study. Dynamic cytosolic Ca2+ changes were measured in individual fluorescent Ca2+ indicator-loaded cells. Amounts of VEGF production were determined by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs)-formed tube networks were quantitatively evaluated as an in vitro angiogenesis assay. A mouse model concurrently bearing EBV-positive/negative xenografts was utilized to evaluate the tumor growth and angiogenesis in vivo.ResultsEBV infection reliably promoted transplanted tumor growth while enhancing angiogenesis. Introduction of EBV into EBV-negative NPC cells increased the EGF-stimulated VEGF production while amplifying the EGF-evoked Ca2+ responses. Inhibition of the EBV-boosted Ca2+ signaling using 2-aminoethyl diphenylborinate (2-APB), a specific SOCE inhibitor, effectively antagonized the EBV-promoted VEGF production and endothelial tube formation in vitro. Pharmacological blockage of SOCE exhibited anti-angiogenic effect in the EBV-positive xenografts.ConclusionSOCE can serve as a candidate pharmacological target for treating NPC, as blockage of the Ca2+ signaling via SOCE is a feasible strategy to suppress the EBV-driven malignant profiles in NPC cells.

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Small cell carcinoma of the cervix (SCCC) is a rare primary neuroendocrine cervical carcinoma with a high degree of invasiveness. SCCC is prone to early-stage lymph node and distant metastases and characterized by a poor prognosis. Currently, there is no standard treatment. This study aimed to evaluate the clinicopathological factors and treatment models that influence SCCC prognosis through a systematic review and meta-analysis, to improve the diagnosis and treatment of SCCC. A comprehensive search was performed in multiple medical literature databases to retrieve studies on the clinical prognosis of SCCC published in China and abroad as of March 1, 2017. Twenty cohort studies with 1904 patients were analyzed. Meta-analysis showed statistical significance for the following factors: FIGO staging (hazard ratio [HR] = 2.63, 95% confidence interval [CI]: 2.13–3.24; odds ratio [OR] = 3.72, 95% CI: 2.46–5.62), tumor size (HR = 1.64, 95% CI: 1.25–2.15), parametrial involvement (HR = 2.40, 95% CI: 1.43–4.05), resection margin (HR = 4.09, 95% CI: 2.27–7.39), lymph node metastasis (OR = 2.09, 95% CI: 1.18–3.71), depth of stromal invasion (HR = 1.99, 95% CI: 1.33–2.97), neoadjuvant chemotherapy (HR = 2.06, 95% CI: 1.14–3.73), and adjuvant chemotherapy (HR = 1.63, 95% CI: 1.26–2.12; OR = 1.48, 95% CI: 1.02–2.16). FIGO staging, tumor size, parametrial involvement, resection margin, depth of stromal invasion, and lymph node metastasis can be used as clinicopathological characteristics for the prediction of SCCC prognosis. Neoadjuvant chemotherapy tended to improve prognosis. Our findings suggest that neoadjuvant chemotherapy plus adjuvant chemotherapy may be the preferred strategy. However, adjuvant radiotherapy appeared to cause no significant improvement in prognosis. Therefore, the clinical application of radiotherapy and the relationship between radiotherapy and clinicopathological factors need to be re-examined. The results of this study should be validated and developed in formal, well-designed multicenter clinical trials.