Tao Zhang

Phosphorylation of IDH1 Facilitates Progestin Resistance in Endometrial Cancer

Abstract The progestin regimen is one of the main therapeutic strategies for women with endometrial cancer who undergo conservative management. Although many patients respond well to initial therapy, progestin‐refractory disease inevitably emerges, and the molecular basis underlying progestin resistance has not been comprehensively elucidated. Herein, they demonstrated progestin results in p38‐dependent IDH1 Thr 77 phosphorylation (pT77‐IDH1). pT77‐IDH1 translocates into the nucleus and is recruited to chromatin through its interaction with OCT6. IDH1‐produced α‐ketoglutarate (αKG) then facilitates the activity of OCT6 to promote focal adhesion related target gene transcription to confer progestin resistance. Pharmacological inhibition of p38 or focal adhesion signaling sensitizes endometrial cancer cells to progestin in vivo. The study reveals p38‐dependent pT77‐IDH1 as a key mediator of progestin resistance and a promising target for improving the efficacy of progestin therapy.

Lymphocyte and macrophage infiltration in omental metastases indicates poor prognosis in advance stage epithelial ovarian cancer

Objective To investigate the prognostic value of immune cells within omental metastases originating from advanced epithelial ovarian cancer (EOC). Methods We performed immunohistochemical analysis to determine the levels of CD4+/CD8+ tumor-infiltrating lymphocytes (TILs) and CD68+ tumor-associated microphages (TAMs) in omental specimens from 100 patients with advanced EOC. Significant prognostic factors, including immune cells and clinical parameters, were assessed by Kaplan–Meier survival analysis and Cox models. Results Cox regression analysis showed that elevated levels of CD68+ TAMs and intra-islet CD4+ TILs in omental metastases were the main risk factors associated with worse survival outcomes for advanced EOC. Moreover, the survival analysis of relationships between omental immune cells and favorable clinical predictors revealed additional prognostic stratification information. Conclusion Omental immune cells (TAMs and TILs) provide alternative prognostic factors in advanced EOC. In contrast to markers of the EOC tumor microenvironment at the primary site, elevated CD68+ TAMs and intra-islet CD4+ TILs in omental metastases serve as negative prognostic markers in advanced EOC and imply an unfavorable outcome.

A Nomogram for Predicting Cancer-Specific Survival in Patients With Stage I Vulvar Squamous Cell Carcinoma: A Study Based on the SEER Database and External Validation

Introduction Vulvar squamous cell carcinoma (VSCC) is a rare but increasingly prevalent gynecological malignancy. This study aimed to identify risk factors for stage I VSCC, which accounts for approximately 70% of VSCC patients, and to develop a nomogram to predict cancer-specific survival (CSS) for this large subgroup. Methods This study analyzed the datasets consisting of public training and independent external validation sets of patients diagnosed with stage I VSCC between 2010 and 2019. Prognostic factors were discerned through Cox regression analyses and the least absolute shrinkage and selection operator (LASSO) method. A nomogram for CSS was developed and evaluated using the C-index, Kaplan-Meier curves, and decision curve analysis (DCA) plots. Results Our analysis revealed variations in predictors of CSS and overall survival (OS) in stage I VSCC cases from the Surveillance, Epidemiology, and End Results (SEER) database. The multivariate Cox model suggested associations between CSS and age, grade, and number of tumors (NMT), while the LASSO model indicated potential roles for age, stage, invasion depth, NMT, and surgical method. The nomogram showed reasonable discriminative ability in the training (C-index: 0.785) and validation cohorts (C-index: 0.729), with supporting Kaplan-Meier and DCA analyses. Conclusion This study proposes a prognostic model for CSS in stage I VSCC, identifying exploratory associations with multifocal tumors and surgical extent. Further prospective studies are needed to validate these findings and clarify their clinical implications.