A protein microarray‐based serum proteomic investigation reveals distinct autoantibody signature in colorectal cancer

Abstract

Purpose Colorectal cancer (CRC) has been reported as the second leading cause of cancer death worldwide. The 5‐year annual survival is around 50%, mainly due to late diagnosis, striking necessity for early detection. This study aims to identify autoantibody in patients’ sera for early screening of cancer. Experimental Design The study used a high‐density human proteome array with approximately 17,000 recombinant proteins. Screening of sera from healthy individuals, CRC from Indian origin, and CRC from middle‐east Asia origin were performed. Bio‐statistical analysis was performed to identify significant autoantibodies altered. Pathway analysis was performed to explore the underlying mechanism of the disease. Results The comprehensive proteomic analysis revealed dysregulation of 15 panels of proteins including CORO7, KCNAB1, WRAP53, NDUFS6, KRT30, and COLGALT2. Further biological pathway analysis for the top dysregulated autoantigenic proteins revealed perturbation in important biological pathways such as ECM degradation and cytoskeletal remodeling etc. Conclusions and Clinical Relevance The generation of an autoimmune response against cancer‐linked pathways could be linked to the screening of the disease. The process of immune surveillance can be detected at an early stage of cancer. Moreover, AAbs can be easily extracted from blood serum through the least invasive test for disease screening.

Integrative Proteomic and Pharmacological Analysis of Colon Cancer Reveals the Classical Lipogenic Pathway with Prognostic and Therapeutic Opportunities

“…The increasing burden of CAC needs multimodal, non-invasive, and severe assessment of the disease using biochemical, molecular, cellular, and high-throughput systems biology approaches. Early detection and management of CAC need a more in-depth review of the condition with highly sensitive and accurate molecular markers that could serve as an essential tool in screening, diagnosis, and prognosis of CAC. , …”

“…Early detection and management of CAC need a more in-depth review of the condition with highly sensitive and accurate molecular markers that could serve as an essential tool in screening, diagnosis, and prognosis of CAC. 10,11 Recent studies have shown multiple genomic and proteomic alterations, including the de novo lipogenesis (DNL) pathway, revealing the heterogeneous nature of the disease at the molecular level. 9,12 Our previous deep proteomics of CAC has also identified the DNL to be dysregulated with the significant upregulation of the critical enzyme fatty acid synthase (FASN).…”

Metaproteomic Analysis of Nasopharyngeal Swab Samples to Identify Microbial Peptides in COVID-19 Patients

“…Orbitrap Fusion Tribrid Mass Spectrometer (Thermo Scientific) coupled to a nanoLC system (Thermo Scientific) was used for PRM experiments . The isolation generated above was imported in the instrument method for PRM and used further for data acquisition.…”

Metaproteomic analysis of nasopharyngeal swab samples to identify microbial peptides and potential co-infection status in COVID-19 patients

“…The MS RAW files from the 2020 MS dataset (PXD020580 and PXD023016), 2021 MS dataset (PXD029300), and blank MS datasets (See section 1 "MS Datasets" in supplement) were converted into Mascot Generic Format (MGF) files using msconvert tool on Galaxy Europe server (usegalaxy.eu). A large microbial protein sequences database was generated using the Uniprot XML Downloader tool within the Galaxy platform [20] to extract sequences for known genera (33,281,528 protein sequences from 72 genera; See section 2 "Protein Sequences Database" in Supplement) and species (242,901 protein sequences from 7 species; See section 2 "Protein Sequences Database" in Supplement) from nasopharyngeal samples. These large databases were merged with the Human SwissProt database (20,361 protein sequences) and contaminant sequences database (116 protein sequences) to generate a large database of protein sequences for further processing (26,269,124 protein sequences).…”

“…Orbitrap Fusion™ Tribrid™ Mass Spectrometer (Thermo Scientific, USA) coupled to a nanoLC system (Thermo Scientific, USA) was used for PRM experiments [33]. The isolation generated above was imported in the instrument method for PRM and used further for data acquisition.…”