Glycosylated protein-related microenvironmental features in breast cancer are associated with patient prognosis.

IF 2.7 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Mammalian Genome Pub Date : 2025-05-24 DOI:10.1007/s00335-025-10137-9

Xiaoxiao Zhong, Jiaxuan Han, Huan Li, Xiangyu Shen, Bowen Yu, Ting Chen, Haobing Li, Jun Li, Jin Pang, Liyuan Qian, Wei Wu, Xiaoliang Tong, Boni Ding

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引用次数: 0

Abstract

The tumor microenvironment (TME) and aberrant glycosylation have been suggested to play key roles in cancer. This study integrated differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA) to identify tumor microenvironment-related genes and construct a TME-risk prognostic signature (TMERS) through LASSO Cox regression. After batch effect removal, 44 TME-prognosis-related genes (TMEPGs) were identified and classified into three molecular subtypes via K-means clustering. The finalized 22-gene TMERS model demonstrated robust prognostic predictive capacity in GEO datasets. The results revealed distinct immune profiles and prognostic stratifications among genetic subtypes and risk groups, confirming that the TMERS is an independent prognostic indicator for breast cancer (BRCA). Glycosyltransferase genes (GTs) have potential therapeutic relevance through immune regulation, with TMEPG member killer cell lectin like receptor B1 (KLRB1) significantly correlated with BRCA prognosis. Cellular experiments demonstrated that KLRB1 overexpression suppressed BRCA cell proliferation and migration. This work establishes a novel prognostic model for BRCA while highlighting KLRB1 as a potential biomarker, providing new insights into TME-targeted therapeutic strategies.

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乳腺癌中糖基化蛋白相关微环境特征与患者预后相关。

肿瘤微环境（tumor microenvironment， TME）和异常糖基化在肿瘤发生中起关键作用。本研究结合差异表达基因（DEGs）和加权基因共表达网络分析（WGCNA），鉴定肿瘤微环境相关基因，并通过LASSO Cox回归构建tme风险预后特征（TMERS）。去除批效应后，鉴定出44个tme预后相关基因（tmepg），并通过K-means聚类将其分为三个分子亚型。最终的22基因TMERS模型在GEO数据集中显示出强大的预后预测能力。结果揭示了不同基因亚型和风险组的不同免疫特征和预后分层，证实了TMERS是乳腺癌（BRCA）的独立预后指标。糖基转移酶基因（GTs）通过免疫调节具有潜在的治疗相关性，TMEPG成员杀伤细胞凝集素样受体B1 （KLRB1）与BRCA预后显著相关。细胞实验表明，KLRB1过表达可抑制BRCA细胞的增殖和迁移。这项工作建立了一种新的BRCA预后模型，同时突出了KLRB1作为潜在的生物标志物，为tme靶向治疗策略提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Mammalian Genome 生物-生化与分子生物学

CiteScore

4.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Mammalian Genome focuses on the experimental, theoretical and technical aspects of genetics, genomics, epigenetics and systems biology in mouse, human and other mammalian species, with an emphasis on the relationship between genotype and phenotype, elucidation of biological and disease pathways as well as experimental aspects of interventions, therapeutics, and precision medicine. The journal aims to publish high quality original papers that present novel findings in all areas of mammalian genetic research as well as review articles on areas of topical interest. The journal will also feature commentaries and editorials to inform readers of breakthrough discoveries as well as issues of research standards, policies and ethics.