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Background: Systemic immune–inflammation index (SII), calculated by immunoinflammatory cell counts of peripheral blood, is considered a predictor of survival outcome in several solid tumors, including gastric cancer (GC). However, there is no study focusing on the prognostic value of SII in the early stage of GC. This study aims to compare prognostic prediction capabilities of several inflammatory indices, nutritional indices, and tumor markers to further verify the superior prognostic value of SII in stage I–II GC patients after surgery. Methods: In this study, 548 patients (358 in the training group and 190 in the validation group) with stage I–II GC after radical surgery were retrospectively analyzed. The peripheral blood indices of interest were SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), advanced lung cancer inflammation index (ALI), systemic inflammation score (SIS), prognostic nutritional index (PNI), body mass index (BMI), albumin, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate-associated antigen 19-9 (CA19-9), and alpha-fetoprotein (AFP). The time-dependent receiver operating characteristic (t-ROC) curves and the area under the curve (AUC) were used to determine the optimal cutoff value and prognostic ability of each parameter. Kaplan–Meier curves and multivariable Cox regression models were used to evaluate independent prognostic factors. The nomogram was constructed based on the result of bidirectional stepwise regression model. Results: The optimal cutoff value of SII was 508.3. The 5-year overall survival rate of the low SII (SII-L) group was significantly higher than that of the high SII (SII-H) group (92% vs. 80%, P < 0.001), especially in the elderly and stage II patients (91% vs. 73%, P = 0.001; 86% vs. 67%, P = 0.003, respectively). The significant prognostic values of SII were consistent in most subgroups. In multivariate analysis, SII and CA19-9 were the only two independent prognostic hematology indices. The AUC value of SII (0.624) was greater than that of CA19-9 (0.528) and other prognostic parameters. Adding SII to the conventional model improved the predictive ability of 5-year overall survival as shown by the significantly increased net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (P = 0.033, P = 0.053, respectively) and modestly improved consistency index (C-index) (increased by 1.6%). External validation of SII-based nomogram demonstrated favorable predictive performance and discrimination. In addition, interactive web dynamic nomogram was published to facilitate clinical use. Conclusion: SII is a simple but powerful index with a high predictive value to predict survival outcome in patients with stage I–II GC after radical operation. The SII-based nomogram can provide intuitive and accurate prognosis prediction of individual patients. [ABSTRACT FROM AUTHOR]

Bladder Urothelial Carcinoma (BLCA) is the major subtype of bladder cancer, and the prognosis prediction of BLCA is difficult. Ferroptosis is a newly discovered iron-dependent cell death pathway. However, the clinical value of ferroptosis-related genes (FRGs) on the prediction of BLCA prognosis is still uncertain. In this study, we aimed to construct a novel prognostic signature to improve the prognosis prediction of advanced BLCA based on FRGs. In the TCGA cohort, we identified 23 differentially expressed genes (DEGs) associated with overall survival (OS) via univariate Cox analysis (all P < 0.05). 8 optimal DEGs were finally screened to generate the prognostic risk signature through LASSO regression analysis. Patients were divided into two risk groups based on the median risk score. Survival analyses revealed that the OS rate in the high-risk group was significantly lower than that in the low-risk group. Moreover, the risk score was determined as an independent predictor of OS by the multivariate Cox regression analysis (Hazard ratio > 1, 95% CI = 1.724-2.943, P < 0.05). Many potential ferroptosis-related pathways were identified in the enrichment analysis in BLCA. With the aid of an external FAHWMU cohort (n = 180), the clinical predication value of the signature was further verified. In conclusion, the prognosis of advanced BLCA could be accurately predicted by this novel FRG-signature. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma and has poor prognosis in the locally advanced stage. Ferroptosis, a relatively new type of cell death, has gained significant attention in recent years. This study aimed to explore the prognostic value of ferroptosis-related genes (FRGs) in ccRCC. In this study, 50 differentially expressed FRGs between ccRCC and adjacent normal kidney tissues were identified, 26 of them correlated with overall survival (OS) (P < 0.05). Eight optimal FRGs were selected by Lasso regression and multivariate Cox regression analysis, and used to construct a new prognostic risk signature to predict the prognosis of ccRCC patients. In addition, the signature passed the validation of prognostic survival analyses by a significant margin, and the risk score was identified as an independent prognostic marker via Cox regression analyses. Further studies indicated that the signature was significantly correlated with immune cell infiltration. Moreover, the levels of eight FRGs were examined in ccRCC. Collectively, the 8-FRG prognostic risk signature helps the clinicians predict the prognosis and OS of the patients, and standardize prognostic assessments. [ABSTRACT FROM AUTHOR]

MicroRNAs are a group of endogenous small non-coding RNAs commonly dysregulated in tumorigenesis, including glioblastoma (GBM), the most malignant brain tumor with rapid proliferation, diffuse invasion, and therapeutic resistance. Accumulating evidence has manifested that miR-1258 exerts an inhibitory role in many human cancers. However, the expression pattern of miR-1258 and its potential function in GBM tumorigenesis remain unclear. In this study, we reported that miR-1258 expression decreased with the ascending pathological grade of glioma, which indicated an unfavorable prognosis of patients. Functional assays revealed an inhibitory effect of miR-1258 on malignant proliferation, therapeutic resistance, migration, and invasion of GBM in vitro. Moreover, xenograft models also suggested a repression effect of miR-1258 on gliomagenesis. Mechanistically, miR-1258 directly targeted E2F1 in 3'-untranslated regions and attenuated E2F1-mediated downstream gene PCNA and MMP2 transcriptions. Furthermore, restoration of E2F1 expression in GBM cells effectively rescued the tumor-suppressive effect of miR-1258. Our studies illustrated that miR-1258 functioned as a tumor suppressor in GBM by directly targeting E2F1, subsequently inhibiting PCNA and MMP2 transcriptions, which contributed to new potential targets for GBM therapy and other E2F1-driven cancers. [ABSTRACT FROM AUTHOR]

Purpose: Genetic mutations may play an important role in the progression and invasion of thyroid carcinoma (TC), and their coexistence may result in mutational synergy. The presence of the BRAFV600E mutation, as well as mutations affecting the TERT promoter, RAS , CHEK2 and RET/PTC , may all have an impact on prognosis. The aim of this study was to explore whether synergy between the coexistent mutations predicts histopathological prognostic factors that influence disease outcome. Methods: A comprehensive literature search of PubMed, Embase and the Cochrane Library, from their inception until January 2020. Primary outcomes included: disease stage, lymph node metastasis, extrathyroidal extension and distant metastasis; while, secondary outcomes included: tumor recurrence, mortality, invasion of thyroid capsule, multiplicity, presented as an odds ratio (OR) with 95% credible intervals (CrI). Results: 27 publications (comprising 9 active intervention arms), involving 8,388 TC patients, were selected. Network meta-analytic estimates of active interventions contrasted with other active interventions, with random effects, were calculated. In terms of outcomes focus on overall TC, BRAFV600E + TERT co-mutation ranked highest for diseases stage (OR = 5.74, 95% CrI: 3.09–10.66), as well as lymph node metastasis, extrathyroidal extension (5.74, 4.06–8.10), tumor recurrence (7.21, 3.59–14.47), and invasion of the thyroid capsule (3.11, 1.95–4.95). BRAFV600E + TERT co-mutation ranked secondary in distant metastasis, mortality, and multiplicity that ranked highest was TERT + RAS or RAS. When we were limited to the study of patients with papillary TC (PTC), BRAFV600E + TERT always ranked highest for primary outcomes: disease stage (6.39, 3.13–13.04), lymph node metastasis, extrathyroidal extension (5.80,3.89–8.64) and distant metastasis (7.33, 3.00–17.89), while BRAFV600E + TERT again ranked highest in secondary outcomes: tumor recurrence (7.23,3.37–15.51), mortality (9.26, 3.02–28.42), invasion of thyroid capsule (3.20,2.01–5.11), and multiplicity. Conclusions: In this molecular marker mutation-based systematic review and network meta-analysis, we found that coexistent BRAFV600E + TERT genetic co-mutations predicted poor histopathological prognosis, including progression, invasion, and metastasis, especially in PTC. For the overall TC, the BRAFV600E + TERT + RAS triple mutations may have a greater impact on the prognosis, and further research should related to potentially important features. This study is registered with PROSPERO, number CRD42019143242. [ABSTRACT FROM AUTHOR]

Background Epstein-Barr virus (EBV) infection may induce immune suppression in several ways, which may influence the proper host response to other pathogens and lead to a bad outcome of critically ill patients. Methods This was a single-center, retrospective, observational study. All patients admitted to an ICU because of respiratory failure were included. EBV detection from lower respiratory tract (LRT) and serum samples were routinely performed. Results Twenty-eight consecutive cases who were admitted to the ICU at high-risk for an infection or clinical signs of an infection were included in our study. Among the 28 patients, 15 were LRT-positive for EBV (53.6%), and 8 were seropositive for EBV (28.6%). Among the LRT EBV-positive patients, pneumonia was the main indication for ICU admission (93.3%), and in LRT EBV-negative patients, acute exacerbation of COPD (AECOPD) was another indication for ICU admission (46.2%). The CD3+ T cell count (especially the CD3+CD8+ T cell count) was lower than the normal range in LRT- and serum EBV-positive patients; these count were in the normal range in EBV-negative patients. The ICU mortality was 32.1% for all patients. The mortality rate was significantly higher in patients who were seropositive for EBV than seronegative patients (62.5% vs 20.0%). No differences were shown between any outcome parameters for LRT EBV-positive and -negative patients. Conclusions This study showed that EBV DNA is detected in LRT and serum samples of a significant number of ICU patients with respiratory failure, and seropositivity for EBV was associated with mortality. This finding maybe correlated with a low CD3+CD8+ T cell count. [ABSTRACT FROM AUTHOR]