Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays
Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/11/2718 |
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| author | María González-González José María Sayagués Luis Muñoz-Bellvís Carlos Eduardo Pedreira Marcello L. R. de Campos Jacinto García José Antonio Alcázar Patrick F. Braz Breno L. Galves Luis Miguel González Oscar Bengoechea María del Mar Abad Juan Jesús Cruz Lorena Bellido Emilio Fonseca Paula Díez Pablo Juanes-Velasco Alicia Landeira-Viñuela Quentin Lecrevisse Enrique Montalvillo Rafael Góngora Oscar Blanco José Manuel Sánchez-Santos Joshua LaBaer Alberto Orfao Manuel Fuentes |
| author_facet | María González-González José María Sayagués Luis Muñoz-Bellvís Carlos Eduardo Pedreira Marcello L. R. de Campos Jacinto García José Antonio Alcázar Patrick F. Braz Breno L. Galves Luis Miguel González Oscar Bengoechea María del Mar Abad Juan Jesús Cruz Lorena Bellido Emilio Fonseca Paula Díez Pablo Juanes-Velasco Alicia Landeira-Viñuela Quentin Lecrevisse Enrique Montalvillo Rafael Góngora Oscar Blanco José Manuel Sánchez-Santos Joshua LaBaer Alberto Orfao Manuel Fuentes |
| author_sort | María González-González |
| collection | DOAJ |
| description | Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (<i>n</i> = 38) and metastatic (<i>n</i> = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers. |
| first_indexed | 2024-03-10T10:51:12Z |
| format | Article |
| id | doaj.art-e468ffae94664263ae7e73fd33932ba7 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T10:51:12Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e468ffae94664263ae7e73fd33932ba72023-11-21T22:12:52ZengMDPI AGCancers2072-66942021-05-011311271810.3390/cancers13112718Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein ArraysMaría González-González0José María Sayagués1Luis Muñoz-Bellvís2Carlos Eduardo Pedreira3Marcello L. R. de Campos4Jacinto García5José Antonio Alcázar6Patrick F. Braz7Breno L. Galves8Luis Miguel González9Oscar Bengoechea10María del Mar Abad11Juan Jesús Cruz12Lorena Bellido13Emilio Fonseca14Paula Díez15Pablo Juanes-Velasco16Alicia Landeira-Viñuela17Quentin Lecrevisse18Enrique Montalvillo19Rafael Góngora20Oscar Blanco21José Manuel Sánchez-Santos22Joshua LaBaer23Alberto Orfao24Manuel Fuentes25Department of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainDepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainDepartment of General & Gastrointestinal Surgery, Salamanca University Hospital-IBSAL, 37007 Salamanca, SpainSystems and Computing Department (COPPE-PESC), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-914, BrazilEngineering Graduate Program, Polytechnique School and COPPE, UFRJ/Federal University of Rio de Janeiro, Rio de Janeiro 21941-972, BrazilDepartment of General & Gastrointestinal Surgery, Salamanca University Hospital-IBSAL, 37007 Salamanca, SpainDepartment of General & Gastrointestinal Surgery, Salamanca University Hospital-IBSAL, 37007 Salamanca, SpainEngineering Graduate Program, Polytechnique School and COPPE, UFRJ/Federal University of Rio de Janeiro, Rio de Janeiro 21941-972, BrazilEngineering Graduate Program, Polytechnique School and COPPE, UFRJ/Federal University of Rio de Janeiro, Rio de Janeiro 21941-972, BrazilDepartment of General & Gastrointestinal Surgery, Salamanca University Hospital-IBSAL, 37007 Salamanca, SpainPathology Service, Salamanca University Hospital-IBSAL, 37007 Salamanca, SpainPathology Service, Salamanca University Hospital-IBSAL, 37007 Salamanca, SpainMedical Oncology Service, Hospital Universitario de Salamanca-IBSAL, 37007 Salamanca, SpainMedical Oncology Service, Hospital Universitario de Salamanca-IBSAL, 37007 Salamanca, SpainMedical Oncology Service, Hospital Universitario de Salamanca-IBSAL, 37007 Salamanca, SpainDepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainDepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainDepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainDepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainDepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainDepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainPathology Service, Salamanca University Hospital-IBSAL, 37007 Salamanca, SpainStatistics Department, University of Salamanca, 37008 Salamanca, SpainVirginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, School of Molecular Sciences, Arizona State University, Tempe, AZ 85281, USADepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainDepartment of Medicine and General Cytometry Service-Nucleus, CIBERONC ISCIII, Cancer Research Center (IBMCC/CSIC/USAL/IBSAL), 37007 Salamanca, SpainSporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (<i>n</i> = 38) and metastatic (<i>n</i> = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.https://www.mdpi.com/2072-6694/13/11/2718metastasescolorectal cancerauto-antibody profilingtumor-associated antigen proteinsNAPPArraysprotein antigen array |
| spellingShingle | María González-González José María Sayagués Luis Muñoz-Bellvís Carlos Eduardo Pedreira Marcello L. R. de Campos Jacinto García José Antonio Alcázar Patrick F. Braz Breno L. Galves Luis Miguel González Oscar Bengoechea María del Mar Abad Juan Jesús Cruz Lorena Bellido Emilio Fonseca Paula Díez Pablo Juanes-Velasco Alicia Landeira-Viñuela Quentin Lecrevisse Enrique Montalvillo Rafael Góngora Oscar Blanco José Manuel Sánchez-Santos Joshua LaBaer Alberto Orfao Manuel Fuentes Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays Cancers metastases colorectal cancer auto-antibody profiling tumor-associated antigen proteins NAPPArrays protein antigen array |
| title | Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays |
| title_full | Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays |
| title_fullStr | Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays |
| title_full_unstemmed | Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays |
| title_short | Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays |
| title_sort | tracking the antibody immunome in sporadic colorectal cancer by using antigen self assembled protein arrays |
| topic | metastases colorectal cancer auto-antibody profiling tumor-associated antigen proteins NAPPArrays protein antigen array |
| url | https://www.mdpi.com/2072-6694/13/11/2718 |
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