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整合功能蛋白质组学和下一代测序技术揭示台湾地区乳腺癌的潜在治疗靶点。

Integrating functional proteomics and next generation sequencing reveals potential therapeutic targets for Taiwanese breast cancer.

作者信息

Ku Wei-Chi, Liu Chih-Yi, Huang Chi-Jung, Liao Chen-Chung, Huang Yen-Chun, Kong Po-Hsin, Chen-Chan Hsieh, Tseng Ling-Ming, Huang Chi-Cheng

机构信息

School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, 242, Taiwan.

Division of Pathology, Cathay General Hospital, Taipei, 106, Taiwan.

出版信息

Clin Proteomics. 2025 Jan 22;22(1):4. doi: 10.1186/s12014-025-09526-8.

Abstract

Integrating functional proteomics and next-generation sequencing (NGS) offers a comprehensive approach to unraveling the molecular intricacies of breast cancer. This study investigates the functional interplay between genomic alterations and protein expression in Taiwanese breast cancer patients. By analyzing 61 breast cancer samples using tandem mass tag (TMT) labeling and mass spectrometry, coupled with whole-exome sequencing (WES) or targeted sequencing, we identified key genetic mutations and their impact on protein expression. Notably, pathogenic variants in BRCA1, BRCA2, PTEN, and PIK3CA were found to be clinically relevant, potentially guiding targeted therapy decisions. Additionally, we discovered trans correlations between specific gene alterations (FANCA, HRAS, PIK3CA, MAP2K1, JAK2) and the expression of 22 proteins, suggesting potential molecular mechanisms underlying breast cancer development and progression. These findings highlight the power of integrating proteomics and NGS to identify potential therapeutic targets and enhance personalized medicine strategies for Taiwanese breast cancer patients.

摘要

整合功能蛋白质组学和下一代测序(NGS)为揭示乳腺癌的分子复杂性提供了一种全面的方法。本研究调查了台湾乳腺癌患者基因组改变与蛋白质表达之间的功能相互作用。通过使用串联质谱标签(TMT)标记和质谱分析61个乳腺癌样本,并结合全外显子测序(WES)或靶向测序,我们确定了关键基因突变及其对蛋白质表达的影响。值得注意的是,发现BRCA1、BRCA2、PTEN和PIK3CA中的致病变体具有临床相关性,可能指导靶向治疗决策。此外,我们发现特定基因改变(FANCA、HRAS、PIK3CA、MAP2K1、JAK2)与22种蛋白质的表达之间存在反式相关性,提示了乳腺癌发生和进展的潜在分子机制。这些发现凸显了整合蛋白质组学和NGS以识别潜在治疗靶点并加强台湾乳腺癌患者个性化医疗策略的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bcb/11753163/f7c38371cb80/12014_2025_9526_Fig1_HTML.jpg

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