Multi-omics analysis of the dynamic role of STAR+ cells in regulating platinum-based chemotherapy responses and tumor microenvironment in serous ovarian carcinoma DOI Creative Commons

Hongwei Lan,

Wei‐Hua Yan, Xiao Hu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Background Serous ovarian carcinoma (SOC) is the most lethal subtype of cancer, with chemoresistance to platinum-based chemotherapy remaining a major challenge in improving clinical outcomes. The role tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), modulating responses not yet fully understood. Methods To explore relationship between CAF subtypes and sensitivity, we employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry (IHC), immunofluorescence (IF). This multi-omics approach enabled identification, characterization, functional analysis both chemotherapy-sensitive chemotherapy-resistant SOC patients. Results We identified steroidogenic acute regulatory protein-positive (STAR+) cells as novel enriched STAR + exhibited unique transcriptional profiles were functionally pathways related P450 drug metabolism, lipid amino acid enhanced pathway activity observed groups. Spatial transcriptomics IF revealed that closely localized cells, suggesting potential cell-cell interactions. Further communication indicated may suppress WNT signaling contributing improved responses. Importantly, expression levels, validated by IHC, positively correlated sensitivity patient prognosis. Platinum-based was shown increase proportion underscoring their dynamic response treatment. Conclusion Our study identifies enhances SOC. By key metabolic potentially suppressing signaling, could contribute treatment These findings position promising biomarker for predicting efficacy SOC, which warrants further investigation.

Language: Английский

Multi-omics analysis of the dynamic role of STAR+ cells in regulating platinum-based chemotherapy responses and tumor microenvironment in serous ovarian carcinoma DOI Creative Commons

Hongwei Lan,

Wei‐Hua Yan, Xiao Hu

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Background Serous ovarian carcinoma (SOC) is the most lethal subtype of cancer, with chemoresistance to platinum-based chemotherapy remaining a major challenge in improving clinical outcomes. The role tumor microenvironment (TME), particularly cancer-associated fibroblasts (CAFs), modulating responses not yet fully understood. Methods To explore relationship between CAF subtypes and sensitivity, we employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry (IHC), immunofluorescence (IF). This multi-omics approach enabled identification, characterization, functional analysis both chemotherapy-sensitive chemotherapy-resistant SOC patients. Results We identified steroidogenic acute regulatory protein-positive (STAR+) cells as novel enriched STAR + exhibited unique transcriptional profiles were functionally pathways related P450 drug metabolism, lipid amino acid enhanced pathway activity observed groups. Spatial transcriptomics IF revealed that closely localized cells, suggesting potential cell-cell interactions. Further communication indicated may suppress WNT signaling contributing improved responses. Importantly, expression levels, validated by IHC, positively correlated sensitivity patient prognosis. Platinum-based was shown increase proportion underscoring their dynamic response treatment. Conclusion Our study identifies enhances SOC. By key metabolic potentially suppressing signaling, could contribute treatment These findings position promising biomarker for predicting efficacy SOC, which warrants further investigation.

Language: Английский

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