Background: Prognostic biomarkers remain a focus in breast cancer during last decades. More reliable predictors to adequately characterize the prognosis of breast cancer are essential. The 2′-5′-oligoadenylate synthetases (OAS), composing of OAS1, OAS2, OAS3, and OAS-like (OASL), are interferon (IFN)-induced antiviral enzymes, with their prognostic roles remain to be characterized. Methods: Prognostic values of OAS family members were assessed by multiple public available resources. Results: High mRNA expression of OAS1 and OAS3 were correlated with worse prognosis for all breast cancer patients, whereas OAS2 was associated with favorable prognosis. The prognostic values of OAS family in different clinicopathologic subtypes were also characterized. In DNA methylation level, cg12560128 in OAS2, cg06800840 and cg26328872 in OASL showed significant prognostic values. The mRNA expression of OAS members signature in high/low risk overall survival groups was opposite to the high/low risk recurrence free survival groups. Neutrophil cell exhibited highest correlation with all OAS members in tumor immune infiltrating estimation. Conclusions: This study provided new insight into the prognostic roles of OAS in breast cancer with potential mechanistic values.
Background: This study was to establish nomogram models for prognostic evaluation of early-onset gastric cancer (EOGC) in both overall survival (OS) and cancer-specific survival (CSS). Methods: EOGC patients from 2004 to 2015 were retrieved from the surveillance, epidemiology and end results (SEER) and further randomly assigned to training and validation sets. Univariate and multivariate cox analysis was used to screen out significant variables for construction of nomogram. Nomogram models were assessed by concordance index (C-index), calibration plot, receiver operating characteristics (ROCs) curve and decision curve analysis (DCA). Results: A total of 549 EOGC were selected in this process. OS nomogram was constructed based on tumor size and tumor site. CSS nomogram was constructed based on tumor size, SEER stage and tumor site. In training set, C-index for the OS nomogram was 0.688 [95% confidence intervals (95% CI): 0.629–0.747], CSS nomogram 0.785 (95% CI: 0.735–0.835). In the external validation, the C-index for the OS nomogram was 0.633 (95% CI: 0.579–0.687), while for the CSS nomogram 0.733 (95% CI: 0.686–0.780). High quality of calibration plots both in OS and OS nomogram models was noticed. Nomograms displayed a comparable result to tumor-node-metastasis (TNM) stage and SEER stage for EOGC based on DCA. Conclusions: The nomogram models provided an insightful and applicable tool to evaluate the prognosis of EOGC both in OS and CSS.
Background: This study aimed to establish nomogram models of overall survival (OS) and cancer-specific survival (CSS) in elderly colorectal cancer (ECRC) patients (Age ≥ 70). Methods: The clinical variables of patients confirmed as ECRC between 2004 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analysis were performed, followed by the construction of nomograms in OS and CSS. Results: A total of 44,761 cases were finally included in this study. Both C-index and calibration plots indicated noticeable performance of newly established nomograms. Moreover, nomograms also showed higher outcomes of decision curve analysis (DCA) and the area under the curve (AUC) compared to American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) stage and SEER stage. Conclusions: This study established nomograms of elderly colorectal cancer patients with distinct clinical values compared to AJCC TNM and SEER stages regarding both OS and CSS.
20 March 2020 in Infection Control & Hospital Epidemiology
Background: The N-myc downstream-regulated gene ( NDRG) family, NDRG1-4, has been involved in a wide spectrum of biological functions in multiple cancers. However, their prognostic values remain sparse in gastric cancer (GC). Therefore, it is crucial to systematically investigate the prognostic values of the NDRG family in GC. Methods: The prognostic values of the NDRG family were evaluated by Kaplan–Meier Plotter and SurvExpress. The mRNA of the NDRG family was investigated in The Cancer Genome Atlas (TCGA). Transcription factors (TFs) and miRNAs associated with the NDRG family were predicted by NetworkAnalysis. The prognostic values of DNA methylation levels were analyzed by MethSurv. The correlation between immune cells and the NDRG family was evaluated by the Tumor Immune Estimation Resource (TIMER) database. Results: High levels of mRNA expression of NDRG2 and NDRG3 were associated with a favorable prognosis in all GCs. In HER2− GC, NDRG1 was significantly associated with a poor prognosis of GC [hazard ratio (HR) = 1.65, 95% confidence interval (CI) = 1.16–2.33, p = 0.0046]. In HER2+ GC, NDRG4 showed a poor prognosis (HR = 1.4, 95% CI: 1.06–1.85, p = 0.017). NDRG4 was an independent prognostic factor in recurrence-free survival by TCGA cohort. The low-risk NDRG-signature group displayed a significantly favorable survival outcome than the high-risk group (HR = 1.76, 95% CI: 1.2–2.59, p = 0.00385). The phosphorylated protein NDRG1 (NDRG1_pT346) displayed a favorable overall survival and was significantly associated with HER2 and phosphorylated HER2. Epidermis development was the top biological process (BP) for coexpressed genes associated with NDRG1 and NDRG4, while mitotic nuclear division and mitotic cell processes were the top BPs for NDRG2 and NDRG3, respectively. Overall, 6 CpGs of NDRG1, 4 CpGs of NDRG2, 3 CpGs of NDRG3 and 24 CpGs of NDRG4 were associated with significant prognosis. CD4+ T-cells showed the highest correlation with NDRG4 (correlation = 0.341, p = 2.14e−11). Furthermore, BCL6 in follicular helper T-cells (Tfh) cells showed the highest association with NDRG4 (correlation = 0.438, p = 00e+00). Conclusions: This study analyzed the multilevel prognostic values and biological roles of the NDRG family in GC.