BackgroundTo build a predictive scoring model based on simple immune and inflammatory parameters to predict postoperative survival in patients with breast cancer.MethodsWe used a brand-new immuno-inflammatory index—pan-immune-inflammation value (PIV)—to retrospectively evaluate the relationship between PIV and overall survival (OS), and based on the results of Cox regression analysis, we established a simple scoring prediction model based on several independent prognostic parameters. The predictive accuracy of the model was evaluated and independently validated.ResultsA total of 1,312 patients were included for analysis. PIV was calculated as follows: neutrophil count (109/L) × platelet count (109/L) × monocyte count (109/L)/lymphocyte count (109/L). According to the best cutoff value of PIV, we divided the patients into two different subgroups, high PIV (PIV > 310.2) and low PIV (PIV ≤ 310.2), associated with significantly different survival outcomes (3-year OS, 80.26% vs. 86.29%, respectively; 5-year OS, 62.5% vs. 71.55%, respectively). Six independent prognostic factors were identified and used to build the scoring system, which performed well with a concordance index (C-index) of 0.759 (95% CI: 0.715–0.802); the calibration plot showed good calibration.ConclusionsWe have established and verified a simple scoring system for predicting prognosis, which can predict the survival of patients with operable breast cancer. This system can help clinicians implement targeted and individualized treatment strategies.

RNA-binding Fox (RBFOX)2, a member of a family of RNA-binding proteins, is well known as a regulator of alternative pre-mRNA splicing. However, its possible role in gastric cancer is unknown. In this study, we investigated the biologic role and clinical significance of RBFOX2 in gastric cancer growth and elucidated its underlying molecular mechanisms. We found that RBFOX2 was highly expressed in gastric cancer cell lines and tumor tissue compared with the adjacent nontumor tissue. We also found that RBFOX2 overexpression was correlated with poor overall survival in patients with gastric cancers. Multivariate survival analyses revealed that higher RBFOX2 expression was an independent prognostic factor for the overall survival of patients with gastric cancers. Suppression of RBFOX2 by shRNA inhibited gastric cancer cell proliferation, colony formation and induced apoptosis. Mechanism studies revealed that these effects were achieved through the simultaneous modulation of multiple signaling pathways. Knockdown of RBFOX2 expression by shRNA markedly inhibited the phosphorylation of phosphatidylinositol 3-hydroxy kinase, threonine kinase and extracellular signal-regulated kinase and Jun N-terminal kinases proteins. In contrast, the ectopic expression of RBFOX2 had the opposite effects. Moreover, RBFOX2 knockdown also induced the cleavage of caspase-3 and caspase-9 proteins. Collectively, these results demonstrate that RBFOX2 plays a critical role in regulating gastric cancer cell proliferation and survival and may be a potential prognostic biomarker and therapeutic target for gastric cancer.

Background: The purpose of this study was to evaluate the benefit to be gained from the addition of local radiotherapy to systemic chemotherapy in patients with newly diagnosed metastatic nasopharyngeal carcinoma in endemic areas of Southern China.Methods: The data of patients with metastatic nasopharyngeal carcinoma (n = 649) were retrospectively analyzed: 313 patients received only chemotherapy and 336 received chemotherapy plus radiotherapy. The characteristics of the radiotherapy and chemoradiotherapy groups were compared using the chi-square test or Fisher exact test. Survival was analyzed using the Kaplan–Meier method. A Cox proportional hazard model was used to identify the factors independently associated with survival.Results: Median follow-up was for 36 months. In univariate analysis, radiotherapy was significantly associated with improved survival (median OS 27 vs. 18 months; 5-year OS 36.4% vs. 20.1%; P < 0.001). In multivariate analysis, radiotherapy was an independent predictor of survival (HR, 0.65; CI, 0.53-0.79; P < 0.001). Other independent prognostic factors included number of metastatic organs, smoking, body mass index, hemoglobin, and N stage. In subgroup analysis, chemoradiotherapy was associated with improved survival in both the single-organ metastasis group (5-year OS, 38.5% vs. 25.1%; P < 0.001) and the multiorgan metastases group (5-year OS, 25.0% vs. 9.7%; P = 0.003）.Conclusion: The addition of local radiotherapy to chemotherapy appears to improve survival in patients with metastatic nasopharyngeal carcinoma. Even patients with multiorgan metastases may benefit from radiotherapy.

Background: Serine hydroxymethyltransferase 2 (SHMT2) is a key enzyme in Serine/glycine metabolism. SHMT2 is very important for tumor cell growth and proliferation as well as metabolism. Here, we investigated the regulatory effects of SHMT2 on breast cancers growth and identified the underlying mechanisms of functions.Methods: We detected the expression of SHMT2 in breast cancer cells and tissues by immunohistochemistry and Western blotting.We investigated the functional and molecular mechanisms by which SHMT2 downregulation or overexpression regulates the growth and apoptosis of breast cancer cells in vivo and in vitro. Results: We found SHMT2 was highly expressed in BRCA cell lines and tumor tissues. Strong SHMT2 expression showed a positive correlation with the poor prognoses of patients with breast cancers. SHMT2 knockdown by shRNA significantly inhibited cell growth and induced apoptosis in vitro, and whereas SHMT2 overexpression promoted tumor growthin in subcutaneous xenograft model. RNA-seq revealed that high expression of SHMT2 not only promoted serine metabolism, nucleotide metabolism, oxidative phosphorylation and proteasome independent degradation pathways. It also activated the cell survival signaling pathway and antagonized the apoptosis pathway. The observed molecular regulation of cell growth was accompanied by the activited of the MAPK, VEGF pathways and suppressed of the mitochondrial mediated apoptosis pathway that was mediated by the SHMT2 up-regulation. Conclusions: These results indicate that SHMT2 plays a critical role in regulating breast cancers growth and could serve as a therapeutic target for breast cancer therapy.