Single-cell transcriptomics reveals the aggressive landscape of high-grade serous carcinoma and therapeutic targets in tumor microenvironment

被引：8

作者：

Xu, Junfen ^{[1
,2
]}

Lu, Weiguo ^{[1
,2
]}

Wei, Xinyi ^{[1
]}

Zhang, Bo ^{[3
]}

Yang, Haihua ^{[3
]}

Tu, Mengyan ^{[1
]}

Chen, Xin ^{[1
]}

Wu, Shenglong ^{[1
]}

Guo, Tianchen ^{[1
]}

机构：

[1] Zhejiang Univ, Womens Hosp, Sch Med, Dept Gynecol Oncol, Hangzhou 310006, Zhejiang, Peoples R China

[2] Zhejiang Prov Clin Res Ctr Obstet & Gynecol, Hangzhou 310006, Zhejiang, Peoples R China

[3] Novel Bioinformat Co Ltd, Shanghai, Peoples R China

来源：

CANCER LETTERS | 2024年 / 593卷

关键词：

OVARIAN-CANCER; EXPRESSION; TRANSFORMATION; DISSECTION; PATTERNS; INVASION; MUTATION;

D O I：

10.1016/j.canlet.2024.216928

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

High-grade serous carcinoma (HGSC) is characterized by early abdominal metastasis, leading to a dismal prognosis. In this study, we conducted single -cell RNA sequencing on 109,573 cells from 34 tumor samples of 18 HGSC patients, including both primary tumors and their metastatic sites. Our analysis revealed a distinct S100A9 + tumor cell subtype present in both primary and metastatic sites, strongly associated with poor overall survival. This subtype exhibited high expression of S100A8, S100A9, ADGRF1, CEACAM6, CST6, NDRG2, MUC4, PI3, SDC1, and C15orf48. Individual knockdown of these ten marker genes, validated through in vitro and in vivo models, significantly inhibited ovarian cancer growth and invasion. Around S100A9 + tumor cells, a population of HK2 + _CAF was identified, characterized by activated glycolysis metabolism, correlating with shorter overall survival in patients. Notably, similar to CAFs, immunosuppressive tumor -associated macrophage (TAM) subtypes underwent glycolipid metabolism reprogramming via PPARgamma regulation, promoting tumor metastasis. These findings shed light on the mechanisms driving the aggressiveness of HGSC, offering crucial insights for the development of novel therapeutic targets against this formidable cancer.

引用

页数：16

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