BackgroundGastric cancer (GC) is a prevalent cancer with high mortality and strong invasiveness, and the entire regulatory networks of GC is still unclear.ObjectiveThe aim of this study was to explore the specific mechanism of the effect of nucleolar protein 6 (NOL6) on the proliferation and apoptosis of GC cells.MethodsThe human gastric adenocarcinoma cell line HGC-27 and AGS were cultured. qRT-PCR was used to verify the expression level of NOL6 in GC cells; MTT and EdU were used to test cell proliferation; TUNEL staining and Flow cytometry were used to detect cell apoptosis; The downstream genes and pathways following NOL6 knockdown were explored through the microarray assay and ingenuity pathway analysis, and the downstream genes were finally verified by qRT-PCR and Western blotting. The xenograft mice were used to investigate the effect of NOL6 on GC in vivo.ResultsTCGA data analysis showed that NOL6 expression level was higher in GC cells than adjacent normal cells. Over-expression of NOL6 increased proliferation and colony formation, and inhibited the apoptotic rate in AGS and HGC-27 cells, while NOL6 knockdown induced the opposite effects. Through microarray assay and IPA analysis, NOL6-related downstream genes and critical signaling pathways were found. And we verified the relationship between downstream genes and GC. Additionally, NOL6 knockdown could decrease the weight and volume of tumor in the mice.ConclusionNOL6 knockdown could inhibit cell proliferation and induce cell apoptosis of GC, suggesting that NOL6 may serve as a potential therapeutic target for treating GC.
Background
The aim of this study was to develop comprehensive and effective nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) rates in patients with colorectal mucinous adenocarcinoma (CRMA).
Methods
A total of 4711 CRMA patients who underwent radical surgery between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were collected and randomized into development (n=3299) and validation (n=1412) cohorts at a ratio of 7:3 for model development and validation. OS and CSS nomograms were developed using the prognostic factors from the development cohort after multivariable Cox regression analysis. The performance of the nomograms was evaluated using Harrell’s concordance index (C-index), calibration diagrams, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA).
Results
The study included 4711 patients. Multivariate Cox regression analysis demonstrated that age, tumor size, grade, pT stage, pN stage, M stage, carcinoembryonic antigen, perineural invasion, tumor deposits, regional nodes examined, and chemotherapy were correlated with OS and CSS. Marital status was independently related to OS. In the development and validation cohorts, the C-index of OS was 0.766 and 0.744, respectively, and the C-index of CSS was 0.826 and 0.809, respectively. Calibration curves and ROC curves showed predictive accuracy. DCA showed that the nomograms had excellent potency over the 8th edition of the TNM staging system with higher clinical net benefits. Significant differences in OS and CSS were observed among low-, medium-, and high-risk groups.
Conclusions
Nomograms were developed for the first time to predict personalized 1-, 3-, and 5-year OS and CSS in CRMA postoperative patients. External and internal validation confirmed the excellent discrimination and calibration ability of the nomograms. The nomograms can help clinicians design personalized treatment strategies and assist with clinical decisions.
The principal treatment modalities for esophageal cancer are radiation, chemotherapy and surgery or a combination of them. In some sense, technological advances have tremendously heightened patients’ survival rates. Nevertheless, the debate on the prognostic value of postoperative radiotherapy (PORT) has never ceased. On that account, this study made an effort to probe deep into the effects of PORT and surgery on the prognosis of stage III esophageal cancer. Our study included patients diagnosed with stage III esophageal cancer between 2004 and 2015 through the Surveillance, Epidemiology, and End Results (SEER) program. We performed propensity score matching (PSM) on the basis of whether surgery was carried out and whether PORT conducted. We identified the independent risk factors by multivariate Cox regression and constructed a nomogram model. In this research, we included 3940 patients, and the median follow-up is 14 months: 1932 cases without surgery; 2008 cases with surgery, and 322 cases of them underwent PORT. In the postPSM patient cohort, patients who underwent surgery had a median overall survival rate (OS) of 19.0 (95% confidence interval [CI] 17.2–20.8) and a median cancer-specific survival rate (CSS) of 23.0 (95% CI 20.6–25.3) months, which were remarkably higher than those without surgery (P < .001). The OS(P < .05)and CSS(P < .05)of the patients who underwent PORT were lower than those who did not. Similar results were obtained in the groups of N0 and N1. This study revealed surgery can heighten patients’ survival rate, while PORT could not elevate patients’ survival rate in stage III esophageal cancer patients.
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