ObjectiveHepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis, and limited therapy options, resulting in a poor prognosis. Cell division cycle associated 2 (CDCA2), also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear.MethodsThe differentially expressed genes that were significantly upregulated in multiple RNA sequencing datasets of HCC were screened. Receiver operating characteristic (ROC) curve analysis was performed to identify diagnostic markers for HCC. Least absolute shrinkage and selection operator Cox regression analysis was performed to screen the prognosis-related genes. The screening and analyses identified CDCA2 as the target gene in this study. The expression of CDCA2 was analyzed in public databases and clinical specimens, and CDCA2 involvement in HCC was explored by both bioinformatic analysis and in vitro experiments.ResultsThe level of CDCA2 was enhanced in HCC compared with healthy livers. Overexpression of CDCA2 positively correlated with the pathological grade and TNM stage of the diseases. Furthermore, CDCA2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with CDCA2 in combination with TNM stage. Bioinformatic analysis revealed that CDCA2 was closely associated with the cell cycle, apoptosis, and p53 signaling pathway. Silencing CDCA2 in Huh7 cells resulted in significant upregulation of p53 and the downstream PUMA and NOXA and a subsequently increased apoptosis. Inhibition of p53 signaling and apoptosis was found after overexpression of CDCA2 in L02 cells. Strikingly, the proliferation of cells was not affected by CDCA2.ConclusionsCDCA2 was a novel diagnostic marker for HCC, and overexpression of this gene reflected poor pathological grade, stage, and clinical prognosis. CDCA2 promoted the pathogenesis of HCC by suppressing the p53-PUMA/NOXA signaling and the subsequent apoptosis.
Background/Aims: The aim of our study was to develop and validate a nomogram to predict cancer-specific survival and make a risk stratification system for primary gastrointestinal melanoma. Materials and Methods: Patients with primary gastrointestinal melanoma in the Surveillance, Epidemiology, and End Results database between 2000 and 2018 were included and randomly divided into the training and validation cohort (8:2). A prediction nomogram of cancer-specific survival was constructed based on the risk factors identified in the multivariate Cox regression. Calibration curve, time-dependent receiver operating characteristic, and decision curve analysis were performed. Further, a risk stratification system was developed based on the nomogram. Results: A total of 433 patients were included. The nomogram was constructed based on age, site, and tumor size, Surveillance, Epidemiology, and End Results (SEER) stage, and therapy. The area under the curves of the nomogram predicting 6-, 12-, and 18-month cancer-specific survival were 0.789, 0.757, and 0.726 for the internal validation and 0.796, 0.763, and 0.795 for the external validation. Calibration curves and decision curve analysis were performed. Further, patients were divided into 2 risk subgroups. The Kaplan–Meier analysis and the log-rank test showed that the risk stratification made well differentiation of patients with different risks of cancer-specific survival. Conclusion: We developed and validated a practical prediction model of cancer-specific survival and a risk stratification system for patients with primary gastrointestinal melanoma, which might be available in clinical practices.
AimTo identify the association between endoscopic primary prophylaxis and the risk of rebleeding in patients with liver cirrhosis receiving endoscopic therapy.MethodsThis cohort study involved in 944 liver cirrhosis patients with esophagogastric variceal bleeding (EGVB) receiving endoscopic therapy. All participants were divided into two groups: rebleeding group (n = 425) and non-rebleeding group (n = 519) according to the occurrence of rebleeding in patients. Rebleeding indicated any bleeding after endoscopic therapy for the first bleeding of esophagogastric varices in liver cirrhosis patients. Univariate and multivariate logistic analyses were employed to identify the association between endoscopic primary prophylaxis and rebleeding in patients with liver cirrhosis after endoscopic therapy.ResultsIn total, 425 patients rebleeded at the end of the follow-up. The risk of rebleeding in patients with endoscopic primary prophylaxis decreased by 0.773 times (OR = 0.227, 95%CI: 0.139–0.372, P < 0.001) after adjusting covariables. Subgroups were divided according to the Child-Pugh (CP) score, and the results revealed that the risk of rebleeding in patients with endoscopic primary prophylaxis decreased by 0.858 times in Grade A patients (OR = 0.142, 95%CI: 0.066–0.304, P < 0.001) and 0.804 times in Grade B patients (OR = 0.196, 95%CI: 0.085–0.451, P < 0.001) compared with patients without endoscopic primary prophylaxis, but showed no difference in Grade C patients.ConclusionEndoscopic primary prophylaxis was associated with a decreased risk of rebleeding in liver cirrhosis patients with EGVB after endoscopic therapy, which suggested that clinicians should pay more attention to endoscopic primary prophylaxis to prevent the occurrence of rebleeding in these patients.
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