Proteomic landscape of colorectal cancer liver metastasis

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.

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.

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.

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.