Proteomics and liquid biopsy characterization of human EMT-related metastasis in colorectal cancer

ABSTRACT: Tumor cells undergo epithelial-mesenchymal transition (EMT), however, there is a room of disagreement in role of EMT heterogeneity to colorectal cancer metastasis (mCRC) evolution. To uncover new EMT-related metastasis proteins and pathways, we addressed the EMT status in colorectal cancer liver metastasis patient-derived CTCs to identify proteins that promote their distant metastasis. And then, we performed a comparative proteomic analysis in matched pairs of primary tumor tissues, adjacent mucosa tissues and liver metastases tissues. By integrative analysis we show that, unstable Epithelial/Mesenchymal (E/M)-type CTCs had the strongest liver metastases formation ability and the proportion of E/M-type CTCs correlated with distant metastases. Using an optimized proteomic workflow including data independent acquisition (DIA) and parallel reaction monitoring (PRM), we identified novel EMT-related protein cluster (e.g., GNG2, COL6A1, COL6A2, DCN, COL6A3, LAMB2, TNXB, CAVIN1) and well-described (e.g., KRAS and ERBB2) core protein level changes in EMT-related metastasis progression, and the proteomic data indicate KRAS, ERBB2, COL6A1 and CAVIN1 are promising EMT-related metastatic biomarker candidates. This study contributes to catch on EMT in CRC metastasis and in favor of heterogeneous EMT phenotypes as a key piece for tumor outcome and treatment. We further propose that therapies targeting this aggressive subset (E/M-type) of CTCs and related protein may be worthy of exploration as potential suppressors of metastatic evolution

ORGANISM(S): Homo Sapiens

SUBMITTER: Linhai Yan  

PROVIDER: PXD033788 | iProX | Mon May 09 00:00:00 BST 2022

REPOSITORIES: iProX