Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers.
Elucidating the susceptibility to breast cancer: an in-depth proteomic and transcriptomic investigation into novel potential plasma protein biomarkers.
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DOI：
10.3389/fmolb.2023.1340917
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发表时间：
2023
影响因子：
5
通讯作者：
中科院分区：
文献类型：
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目的：本研究旨在通过结合孟德尔随机化的蛋白质组和转录组关联研究来鉴定与乳腺癌相关的血浆蛋白。 研究方法：利用高通量数据集，我们设计了一个两阶段的分析框架，旨在识别与乳腺癌相关和致病的新型血浆蛋白。最初，我们进行了蛋白质组/转录组关联研究（P/TWAS），以鉴定具有显著关联的血浆蛋白。随后，孟德尔随机化被用来确定因果关系。通过外部验证和各种敏感性分析，包括贝叶斯共定位，Steiger过滤，异质性和多效性，我们的研究结果的有效性和鲁棒性得到进一步加强。此外，我们对鉴定的蛋白质进行了功能富集分析，以更好地了解它们在乳腺癌中的作用，并评估它们作为可药用靶点的潜力。 结果：我们鉴定了5种血浆蛋白，它们与乳腺癌有很强的相关性和因果关系。具体而言，PEX 14（OR = 1.201，p = 0.016）和CTSF（OR = 1.114，p < 0.001）均显示与乳腺癌呈正相关和因果关系。相反，SNUPN（OR = 0.905，p < 0.001）、CSK（OR = 0.962，p = 0.038）和PARK 7（OR = 0.954，p < 0.001）与疾病呈负相关。对于ER阳性亚型，鉴定了3种血浆蛋白，其中CSK和CTSF表现出一致的趋势，而GDI 2（OR = 0.920，p < 0.001）与该亚型不同。在ER阴性亚型中，PEX 14（OR = 1.645，p < 0.001）作为唯一的蛋白质突出，甚至显示出比乳腺癌更强的因果作用。这些关联得到了共定位和敏感性分析的有力支持。 结论：整合多个数据维度，我们的研究成功地确定了与乳腺癌显著相关和致病的血浆蛋白，为未来的研究和潜在的新生物标志物和治疗靶点提供了有价值的见解。
Objectives: This study aimed to identify plasma proteins that are associated with and causative of breast cancer through Proteome and Transcriptome-wide association studies combining Mendelian Randomization. Methods: Utilizing high-throughput datasets, we designed a two-phase analytical framework aimed at identifying novel plasma proteins that are both associated with and causative of breast cancer. Initially, we conducted Proteome/Transcriptome-wide association studies (P/TWAS) to identify plasma proteins with significant associations. Subsequently, Mendelian Randomization was employed to ascertain the causation. The validity and robustness of our findings were further reinforced through external validation and various sensitivity analyses, including Bayesian colocalization, Steiger filtering, heterogeneity and pleiotropy. Additionally, we performed functional enrichment analysis of the identified proteins to better understand their roles in breast cancer and to assess their potential as druggable targets. Results: We identified 5 plasma proteins demonstrating strong associations and causative links with breast cancer. Specifically, PEX14 (OR = 1.201, p = 0.016) and CTSF (OR = 1.114, p < 0.001) both displayed positive and causal association with breast cancer. In contrast, SNUPN (OR = 0.905, p < 0.001), CSK (OR = 0.962, p = 0.038), and PARK7 (OR = 0.954, p < 0.001) were negatively associated with the disease. For the ER-positive subtype, 3 plasma proteins were identified, with CSK and CTSF exhibiting consistent trends, while GDI2 (OR = 0.920, p < 0.001) was distinct to this subtype. In ER-negative subtype, PEX14 (OR = 1.645, p < 0.001) stood out as the sole protein, even showing a stronger causal effect compared to breast cancer. These associations were robustly supported by colocalization and sensitivity analyses. Conclusion: Integrating multiple data dimensions, our study successfully pinpointed plasma proteins significantly associated with and causative of breast cancer, offering valuable insights for future research and potential new biomarkers and therapeutic targets.
DOI：
10.1007/s00262-017-2047-2
发表时间：
2017-12
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Shuptrine CW;Ajina R;Fertig EJ;Jablonski SA;Kim Lyerly H;Hartman ZC;Weiner LM
通讯作者：
Weiner LM
影响因子：
--
作者：
Huang K;Wu Y;Xie Y;Huang L;Liu H
通讯作者：
Liu H