Integrating plasma proteome with genome reveals novel protein biomarkers in colorectal cancer.

IF 2.8 3区 医学 Q2 ONCOLOGY
Clinical & Translational Oncology Pub Date : 2025-02-01 Epub Date: 2024-07-17 DOI:10.1007/s12094-024-03616-z
Changchun Ye, Leizhou Xia, Ruimin Gong, Jingbo Chang, Qi Sun, Jiaxi Xu, Fanni Li
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引用次数: 0

Abstract

Background: Biomarkers for colorectal cancer (CRC) can complement population screening methods, but so far, few plasma proteins have been identified as biomarkers for CRC. This study aims to identify potential protein biomarkers and therapeutic targets for CRC within the proteome range.

Methods: We extracted summary-level data of circulating protein from 7 published genome-wide association studies (GWASs) of plasma proteome for Mendelian randomization (MR), summary-data-based MR (SMR), and co-localization analyses to screen and validate proteins with causal effects in CRC. In addition, we further conducted druggability evaluation, prognosis analysis at the transcriptional level, and enrichment expression at the single-cell level, highlighting the important role of these plasma protein biomarkers in CRC.

Results: We identified 117 plasma protein biomarkers associated with CRC risk, with 9 proteins showing stronger genetic correlations in Bayesian co-localization (PP.H4 > 0.70). Further, we found 26 protein-coding genes already used in targeted drug development and may potentially become therapeutic targets for CRC. In prognosis analysis, the encoding genes of plasma proteins exhibited consistent effects with MR analysis and can serve as prognostic biomarkers for CRC. Additionally, we also found that the differentially expressed proteins are mainly expressed in fibroblasts, endothelial cells, macrophages, and T cells.

Conclusion: Our study has identified plasma protein biomarkers associated with CRC risk, which may complement population screening methods for CRC and achieve more precise treatment for patients.

Abstract Image

血浆蛋白质组与基因组的整合揭示了结直肠癌的新型蛋白质生物标记物。
背景:大肠癌(CRC)的生物标志物可以补充人群筛查方法,但迄今为止,很少有血浆蛋白被确定为 CRC 的生物标志物。本研究的目的是在蛋白质组范围内确定潜在的蛋白质生物标志物和 CRC 的治疗靶点:方法:我们从 7 项已发表的血浆蛋白质组全基因组关联研究(GWAS)中提取了循环蛋白的摘要级数据,进行了孟德尔随机化(MR)、基于摘要数据的 MR(SMR)和共定位分析,以筛选和验证在 CRC 中具有因果效应的蛋白质。此外,我们还进一步进行了可药性评估、转录水平的预后分析以及单细胞水平的富集表达,强调了这些血浆蛋白生物标志物在 CRC 中的重要作用:结果:我们发现了117个与CRC风险相关的血浆蛋白生物标记物,其中9个蛋白在贝叶斯共定位中显示出较强的遗传相关性(PP.H4 > 0.70)。此外,我们还发现了 26 个已用于靶向药物开发的蛋白编码基因,它们有可能成为 CRC 的治疗靶点。在预后分析中,血浆蛋白的编码基因与 MR 分析显示出一致的效果,可作为 CRC 的预后生物标志物。此外,我们还发现差异表达的蛋白主要在成纤维细胞、内皮细胞、巨噬细胞和T细胞中表达:结论:我们的研究发现了与 CRC 风险相关的血浆蛋白生物标志物,这可能会补充 CRC 的人群筛查方法,并为患者提供更精确的治疗。
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
CiteScore
6.20
自引率
2.90%
发文量
240
审稿时长
1 months
期刊介绍: Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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