SWATH‐based proteomics reveals processes associated with immune evasion and metastasis in poor prognosis colorectal tumours

• Published in: Journal of cellular and molecular medicine 2019-12, Vol.23 (12), p.8219-8232
• Main Authors: López‐Sánchez, Laura M., Jiménez‐Izquierdo, Rafael, Peñarando, Jon, Mena, Rafael, Guil‐Luna, Silvia, Toledano, Marta, Conde, Francisco, Villar, Carlos, Díaz, César, Ortea, Ignacio, De la Haba‐Rodríguez, Juan R., Aranda, Enrique, Rodríguez‐Ariza, Antonio
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer therapies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - classification; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Consortia; Drug development; Epigenetics; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Ontology; Gene Regulatory Networks; Histone deacetylase; Humans; Immune Evasion; Immunosuppressive agents; Kaplan-Meier Estimate; Libraries; Male; Medical prognosis; Medical research; mesenchymal; Mesenchyme; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis; Original; Osteopontin; Patients; Peptides; Prognosis; Proteins; Proteome - genetics; Proteome - metabolism; Proteomics; Proteomics - methods; Ribosomal proteins; Software; Studies; SWATH; Tumors; Wound healing
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.14693

Newly emerged proteomic methodologies, particularly data‐independent acquisition (DIA) analysis–related approaches, would improve current gene expression–based classifications of colorectal cancer (CRC). Therefore, this study was aimed to identify protein expression signatures using SWATH‐MS DIA and targeted data extraction, to aid in the classification of molecular subtypes of CRC and advance in the diagnosis and development of new drugs. For this purpose, 40 human CRC samples and 7 samples of healthy tissue were subjected to proteomic and bioinformatic analysis. The proteomic analysis identified three different molecular CRC subtypes: P1, P2 and P3. Significantly, P3 subtype showed high agreement with the mesenchymal/stem‐like subtype defined by gene expression signatures and characterized by poor prognosis and survival. The P3 subtype was characterized by decreased expression of ribosomal proteins, the spliceosome, and histone deacetylase 2, as well as increased expression of osteopontin, SERPINA 1 and SERPINA 3, and proteins involved in wound healing, acute inflammation and complement pathway. This was also confirmed by immunodetection and gene expression analyses. Our results show that these tumours are characterized by altered expression of proteins involved in biological processes associated with immune evasion and metastasis, suggesting new therapeutic options in the treatment of this aggressive type of CRC.