Identification of tumor-associated antigens with diagnostic ability of colorectal cancer by in-depth immunomic and seroproteomic analysis



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Garranzo Asensio, María and San Segundo Acosta, Pablo and Povés Francés, Carmen and Fernández Aceñero, María Jesús and Martínez Useros, Javier and Montero Calle, Ana and Solís Fernández, Guillermo and Sánchez Martínez, Mari Cruz and Rodríguez, Nuria and Cerón, María Ángeles and Fernández Díez, Servando and Domínguez Muñóz, Gemma and Ríos, Vivian de los and Peláez García, Alberto, Alberto and Guzmán Aránguez, Ana Isabel and Barderas, Rodrigo (2020) Identification of tumor-associated antigens with diagnostic ability of colorectal cancer by in-depth immunomic and seroproteomic analysis. Journal of proteomics, 214 . p. 103635. ISSN 1874-3919

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Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related death worldwide. Its diagnosis at early stages would significantly improve the survival of CRC patients. The humoral immune response has been demonstrated useful for cancer diagnosis, predating clinical symptoms up to 3 years. Here, we employed an in-depth seroproteomic approach to identify proteins that elicit a humoral immune response in CRC patients. The seroproteomic approach relied on the immunoprecipitation with patient-derived autoantibodies of proteins from CRC cell lines with different metastatic properties followed by LC-MS/MS. After bioinformatics, we focused on 31 targets of CRC autoantibodies. After WB and IHC validation, ERP44 and TALDO1 showed potential to discriminate disease-free and metastatic CRC patients, and time to recurrence of CRC patients in stage II. Using plasma samples of 30 healthy individuals, 28 premalignant individuals, and 32 CRC patients, nine out of 13 selected targets for seroreactive analysis showed significant diagnostic ability to discriminate either CRC patients or premalignant subjects from controls. Our results suggest that the here defined panel of CRC autoantibodies and their target proteins should be included in CRC blood-based biomarker panels to get a clinically useful blood-based diagnostic signature for CRC detection.
Significance: Colorectal cancer is one of the deadliest cancer types mainly due to its late diagnosis. Its early diagnosis, therefore, is of great importance since it would significantly improve the survival of CRC patients. In our work, the in-depth seroproteomic analysis of colorectal cancer using isolated IgGs from colorectal cancer patients and controls and protein extract of colorectal cancer cells provide the identification of valuable biomarkers with diagnostic and prognostic ability of the disease.

Item Type:Article
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Received 19 September 2019, Revised 2 January 2020, Accepted 5 January 2020, Available online 7 January 2020.

Uncontrolled Keywords:Tumors; Antigens; Cancer diagnosis; Colorectal cancer; Seroproteomic analysis; Immunomic analysis; CRC; IgGs; Biomarkers
Subjects:Sciences > Chemistry > Molecular biology
Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Oncology
ID Code:58701
Deposited On:02 Mar 2020 09:04
Last Modified:02 Mar 2020 09:40

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