结直肠癌肝转移的蛋白质组学研究。

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-09-29 DOI:10.1016/j.tranon.2025.102558

Ju Wu , Linlin Liu , Yaoyuan Chang , Xiaoyu Duan , Xi Chen , He Li , Zheng Wang , Lianyi Guo , Jiajun Yin

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引用次数: 0

摘要

背景：结直肠癌转移，尤其是肝转移，具有显著复杂的多样性，是导致患者死亡的主要原因。尽管其临床重要性，但驱动转移的精确分子机制仍然知之甚少。方法：为了研究转移异质性的分子驱动因素，我们对非转移性（NM）结直肠癌组织以及异时性（MM）和同步性（SM）转移组织进行了全面的蛋白质组学分析。结果：我们的分析揭示了与结直肠癌肝转移相关的独特生物学特征。值得注意的是，我们发现p53介导的过度增生是CRC发生的一个共同的启动因素。此外，代谢失调是结直肠癌肝转移的一个关键标志。重要的是，MM肿瘤表现出抑制铁下垂和TGF-β信号通路的激活，而SM肿瘤表现出抑制WNT信号通路的anoikis和激活，并伴有激活的血管生成。最引人注目的是，CEACAM6被鉴定为唯一一个从NM到MM再到SM表达逐渐减少的蛋白，强调了其在转移进展中的独特作用。结论：这些发现为了解结直肠癌肝转移的分子复杂性提供了新的见解。我们发现CEACAM6作为一种鉴别标志物，突出了其作为诊断标志物和治疗靶点的潜力，为转移性结直肠癌的治疗提供了新的途径。

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Proteomic landscape of colorectal cancer liver metastasis

Background

Colorectal cancer metastasis, especially liver metastasis, is characterized by significant intricate diversity and remains a major contributor to patient mortality. Despite its clinical importance, the precise molecular mechanisms driving metastasis remain poorly understood.

Methods

To investigate the molecular drivers of metastasis heterogeneity, we performed a comprehensive proteomic analysis of non-metastatic (NM) colorectal cancer tissues, as well as metachronous (MM) and synchronous (SM) metastatic tissues.

Results

Our analysis revealed distinct biological features associated with colorectal cancer liver metastasis. Notably, we identified P53-mediated hyperproliferation as a common initiating factor in the occurrence of CRC. Additionally, metabolic dysregulation emerged as a key hallmark of CRC liver metastasis. Importantly, MM tumors exhibited suppressed ferroptosis and activation of the TGF-β signaling pathway, while SM tumors displayed inhibited anoikis and activation of the WNT signaling pathway, accompanied by activated angiogenesis. Most strikingly, CEACAM6 was identified as the only protein exhibiting a stepwise decrease in expression from NM to MM and further to SM, underscoring its unique role in metastatic progression.

Conclusions

These findings provide new insights into the molecular complexities underpinning colorectal cancer liver metastasis. Our identification of CEACAM6 as a differential marker highlights its potential as a diagnosis marker and therapeutic target, offering new avenues for the treatment of metastatic CRC.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.