Alvaro Ingles R. Garces

Proteomic Landscapes of 3D and 2D Models of High-Grade Serous Ovarian Carcinoma: Implications for Carboplatin Response

High-grade serous ovarian carcinoma (HGSOC) is the most common form of ovarian cancer, and finding new treatments remains an unmet need. While drug discovery is typically performed in two-dimensional (2D) monolayers, three-dimensional (3D) culture systems better mimic the in vivo conditions. However, a comprehensive comparison of 3D versus 2D ovarian cancer models is lacking. Here, we quantitatively compared the whole cell proteomic signatures of four ovarian cell lines─PEO1, PEO4, UWB1.289, and UWB1.289+BRCA1─with different status of BRCA genes grown in 2D and 3D. Using isobaric labeling proteomics, we quantified 6404 proteins and identified 371 significantly and commonly altered proteins between 2D and 3D. Proteins upregulated in 3D were enriched for transmembrane transport and NADH:ubiquinone oxidoreductase complex I, while energy metabolism and cell growth pathways also showed dimensionality-dependent changes. Notably, membrane-associated proteins were downregulated in spheroids, particularly EGFR in PEO1. Furthermore, the 3D culture modulated the response to carboplatin, with an increased expression of drug resistance-associated proteins, including NDUF family members in all spheroid models. These findings underscore how culture dimensionality influences both the molecular landscape and the chemotherapeutic response of HGSOC cells and highlights candidate targets for overcoming carboplatin resistance.

Racial Disparities in Endometrial Cancer Incidence and Outcomes in Brazil: Insights From Population-Based Registries

PURPOSE This study aimed to examine trends in the incidence and mortality rates of endometrial cancer (EC) across ethnic groups in Brazil and to analyze the demographic and clinicopathological characteristics associated with these trends. METHODS The incidence of EC was analyzed from 2010 to 2015 using data from Brazilian Population–Based Cancer Registries (PBCRs), including crude rates and annual percentage changes (APCs). Clinical and sociodemographic information from 2000 to 2019 was gathered from Hospital-Based Cancer Registries. Mortality data between 2000 and 2021 were obtained from the National Mortality Information System, allowing for comparisons between White women and Black women. RESULTS From 2010 to 2015, a total of 32,831 new cases of EC were reported across 13 PBCRs, with Black patients accounting for 35.7% of these cases. The median age at diagnosis was 63 years, with Black women diagnosed at a younger age than White women. Black patients experienced a significant increase in incidence rate (APC +6.7% v +3.0%). A greater proportion of Black patients lived without partners (54.0%), had higher rates of alcohol consumption (15%) and smoking (25.8%), and resided in less developed regions (54.6%) with lower education levels (77.5%). From 2000 to 2021, Brazil recorded 72,189 EC-related deaths, showing higher mortality rates among White women (3.8 per 100,000) than Black women (2.4 per 100,000), although the downward trend was steeper among White women (–1.2%) than Black women (–0.6%). CONCLUSION Racial disparities in EC incidence and mortality in Brazil may be closely linked to unfavorable sociodemographic factors faced by Black women. Targeted public health initiatives are critical for improving early detection and access to equitable care for Black women.