遗传2024,Vol.46Issue(10) :871-885.DOI:10.16288/j.yczz.24-167

计算解析异常代谢对乳腺癌微环境重塑的调控机制

Computational dissection of the regulatory mechanisms of aberrant metabolism in remodeling the microenvironment of breast cancer

万羽鑫 朱欣雨 赵宇 孙娜 江天彤妃 徐娟
遗传2024,Vol.46Issue(10) :871-885.DOI:10.16288/j.yczz.24-167

计算解析异常代谢对乳腺癌微环境重塑的调控机制

Computational dissection of the regulatory mechanisms of aberrant metabolism in remodeling the microenvironment of breast cancer

万羽鑫 1朱欣雨 1赵宇 1孙娜 1江天彤妃 1徐娟1
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作者信息

  • 1. 哈尔滨医科大学生物信息科学与技术学院,哈尔滨 150081
  • 折叠

摘要

肿瘤微环境(tumor microenvironment,TME)中T细胞亚群的组成和肿瘤特异的T细胞互作促进了乳腺癌异质性的形成.此外,肿瘤的异常代谢通常与T细胞的抗肿瘤免疫功能失调关联密切,识别影响免疫细胞互作的关键代谢基因能够为乳腺癌治疗提供潜在靶点.本研究利用乳腺癌单细胞转录组数据,重点研究了乳腺癌发展过程中肿瘤特异性T细胞亚群及其互作子网,进一步评估肿瘤特异性激活的T细胞亚群的代谢通路活性.结果显示,肠促胰岛素的合成、分泌和失活的代谢通路以及果糖分解代谢通路显著影响了多个T细胞亚群的互作.整合肿瘤中T细胞显著上调以及影响互作的代谢通路,依此筛选出核心T细胞互作相关的异常代谢基因,并进一步构建乳腺癌风险评估模型.利用异常代谢显著相关预后基因表达谱与药物IC50值预测靶向药物,最终获得潜在靶向药物GSK-J4、PX-12等.本研究整合分析乳腺癌微环境中T细胞互作的重塑与代谢通路异常在癌症恶性进展中的作用,为新型乳腺癌抗癌疗法提供线索.

Abstract

The composition of T cell subsets and tumor-specific T cell interactions within the tumor microenvironment(TME)contribute to the heterogeneity observed in breast cancer.Moreover,aberrant tumor metabolism is often intimately linked to dysregulated anti-tumor immune function of T cells.Identifying key metabolic genes that affect immune cell interactions thus holds promise for uncovering potential therapeutic targets in the treatment of breast cancer.This study leverages single-cell transcriptomic data from breast cancer to investigate tumor-specific T-cell subsets and their interacting subnetworks in the TME during cancer progression.We further assess the metabolic pathway activities of tumor-specifically activated T-cell subsets.The results reveal that metabolic pathways involved in insulin synthesis,secretion,degradation,as well as fructose catabolism,significantly influence multiple T cell interactions.By integrating the metabolic pathways that significantly up-regulate T cells in tumors and influence their interactions,we identify key abnormal metabolic genes associated with T-cell collaboration and further develop a breast cancer risk assessment model.Additionally,using gene expression profiles of prognosis-related genes significantly associated with aberrant metabolism and drug IC50 values,we predict targeted drugs,yielding potential candidates like GSK-J4 and PX-12.This study integrate the analysis of abnormal T-cell interactions and metabolic pathway abnormalities in the breast cancer TME,elucidating their roles in cancer progression and providing leads for novel breast cancer therapeutic strategies.

关键词

乳腺癌/微环境重塑/异常代谢/T细胞互作

Key words

breast cancer/microenvironmental remodelling/aberrant metabolism/T-cell interactions

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基金项目

国家自然科学基金项目(32170676)

出版年

2024
遗传
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传

CSTPCD北大核心
影响因子:1.082
ISSN:0253-9772
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