BIBR-1532

Background: Endometriosis results in dysmenorrhea, dyspareunia, chronic pelvic pain and infertility in reproductive-age women. However, no effective treatment methods have been applied to the disease, and the pathogenesis of endometriosis is unclear. Purpose: This study was performed to investigate the association between telomere maintenance and endometriosis development. Materials and methods: The telomere length of the postmenopausal endometria, eutopic endometria and their matched ectopic lesions in the proliferative and secretory phases was detected using fluorescence in situ hybridization (FISH) methods, and the effect of telomere length maintenance on the proliferation of endometrial cells derived from endometriotic patients was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with BIBR1532 treatment. Then all of the telomere maintenance genes were extracted from the Telnet database, and bioinformatics analysis was performed to uncover the role of telomere maintenance genes in endometriosis development. Results: Telomere length was longer in endometriotic patients' eutopic endometria during the proliferative and secretory phases, and treatment with a telomerase inhibitor inhibited the proliferation of epithelial cells and stromal cells. Furthermore, the telomere maintenance genes were enriched in several hormone-related pathways, with several genes differentially expressed between normal endometria and endometria derived from endometriotic patients. The nomogram constructed based on telomere maintenance genes also displayed good predictive value. Conclusions: Telomere maintenance may contribute to the development of endometriosis, with several related genes involved.

Gastric cancer remains a common malignancy with poor prognosis. While lactate metabolism is recognized as a significant factor in tumor progression, its potential as a predictive tool for treatment response remains unexplored. This study introduces a novel Lactate-Related Gene Signature (LRGS) designed to predict both survival outcomes and therapy responses in gastric cancer patients.

We comprehensively analyzed 335 lactate-related genes from 11 metabolic pathways using MSigDB, identifying 278 differentially expressed genes between gastric cancer and normal tissues. Employing the LASSO Cox regression model, we developed an innovative LRGS formula based on the expression of 16 key lactate-related genes. The impact of Solute Carrier Family 5 Member 12 (SLC5A12), a gene of particular interest, on gastric cancer cell functions was evaluated using in vitro assays and an in vivo zebrafish model.

Our newly established LRGS demonstrated robust capability in stratifying gastric cancer patients by survival risk. Notably, the LRGS-low subtype showed significantly improved overall and disease-free survival rates compared to the LRGS-high subtype. A key finding was LRGS's ability to predict patient responses to both adjuvant chemotherapy and immunotherapy. Random forest analysis identified SLC5A12 as the most significant gene differentiating gastric cancer from normal tissues. Functional experiments confirmed SLC5A12's role in promoting gastric cancer cell proliferation, invasion, and migration both in vitro and in vivo.

The LRGS is a dependable and efficient prognostic tool for assessing the survival outcomes in individuals with gastric cancer, as well as a predictor of patient response to adjuvant chemotherapy and immunotherapy.