CPE correlates with poor prognosis in gastric cancer by promoting tumourigenesis.

Aims: To investigate the potential functions and mechanisms of tumourigenesis in carboxypeptidase E (CPE) and its prognostic value in gastric cancer, and to develop a predictive model for prognosis based on CPE. Results: Transcriptome level variation and the prognostic value of CPE in different types of cancers were investigated using bioinformatics analyses. The association between CPE and clinicopathological characteristics was specifically explored in gastric cancer. Elevated CPE expression was associated with poor survival and recurrence prognosis and was found in cases with a later clinical stage of gastric cancer. The CPE was considered an independent prognostic factor, as assessed using Cox regression analysis. The prognostic value of CPE was further verified through immunohistochemistry and haematoxylin staining. Enrichment analysis provided a preliminary confirmation of the potential functions and mechanisms of CPE. Immune cell infiltration analysis revealed a significant correlation between CPE and macrophage infiltration. Eventually, a prognosis prediction nomogram model based on CPE was developed. Conclusion: CPE was identified as an independent biomarker associated with poor prognosis in gastric cancer. This suggests that CPE overexpression promoted epithelial-mesenchymal transition via the activation of the Erk/Wnt pathways, leading to proliferation, invasion, and metastasis. Targeted therapeutic strategies for gastric cancer may benefit from these findings.

Constructing and Validating a Dynamic Nomogram to Predict Response to Bariatric Surgery: A Multicenter Retrospective Study.

PURPOSE: Suboptimal response is one of the major problems for bariatric surgery, and constructing an individualized model for predicting outcomes of bariatric surgery is essential. Thus, the aim of this study is to develop a nomogram to predict the response to bariatric surgery. MATERIALS AND METHODS: 509 patients who underwent bariatric surgery between 2019 to 2020 from 6 centers were retrieved and assessed. Multiple Imputation was used to replace missing data. Patients with %TWL ≥ 20% 1 year after bariatric surgery were classified as patients with optimal response, while the others were patients with suboptimal response. A web-based nomogram was constructed and validated. ROC curve and calibration curve were used to determine the predictive ability of our model. RESULTS: 56 (11.0%) patients were classified as patients with suboptimal response, and they showed advanced age, lower pre-operative BMI, smaller waist circumference, higher fasting glucose, higher HbA1c and lower fasting insulin compared to patients with optimal response. A forward likelihood ratio logistic regression analysis indicated that age (OR = 0.943, 95% CI: 0.915-0.971, p < 0.001), pre-operative BMI (OR = 1.109, 95% CI: 1.002-1.228, p = 0.046) and waist circumference (OR = 1.043, 95% CI: 1.000-1.088, p = 0.048) were essential factors contributing to the response to bariatric surgery. Lastly, a web-based nomogram was constructed to predict the response to bariatric surgery and demonstrated an AUC of 0.829 and 0.798 upon internal and external validation. CONCLUSION: Age, BMI and fasting glucose were proved to be essential factors influencing the response to bariatric surgery. The nomogram constructed in this study demonstrated good adaptivity.

Targeting histone demethylases as a potential cancer therapy (Review).

Post­translational modifications of histones by histone demethylases have an important role in the regulation of gene transcription and are implicated in cancers. Recently, the family of lysine (K)­specific demethylase (KDM) proteins, referring to histone demethylases that dynamically regulate histone methylation, were indicated to be involved in various pathways related to cancer development. To date, numerous studies have been conducted to explore the effects of KDMs on cancer growth, metastasis and drug resistance, and a majority of KDMs have been indicated to be oncogenes in both leukemia and solid tumors. In addition, certain KDM inhibitors have been developed and have become the subject of clinical trials to explore their safety and efficacy in cancer therapy. However, most of them focus on hematopoietic malignancy. This review summarizes the effects of KDMs on tumor growth, drug resistance and the current status of KDM inhibitors in clinical trials.