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Volume 12
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Article

Immune-Complexome Analysis Identifies Immunoglobulin-Bound Biomarkers That Predict the Response to Chemotherapy of Pancreatic Cancer Patients

by
Giorgia Mandili
1,2,†,
Laura Follia
1,2,3,†,
Giulio Ferrero
3,4,
Hiroyuki Katayama
5,
Wang Hong
5,
Amin A. Momin
5,
Michela Capello
5,
Daniele Giordano
2,
Rosella Spadi
6,
Maria Antonietta Satolli
6,
Andrea Evangelista
7,
Samir M. Hanash
5,
Francesca Cordero
3 and
Francesco Novelli
1,2,7,*
1
Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Torino, Italy
2
Center for Experimental Research and Medical Studies (CeRMS), University of Turin, 10126 Torino, Italy
3
Department of Computer Science, University of Turin, 10149 Torino, Italy
4
Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, 10043 Orbassano, Turin, Italy
5
MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA
6
Centro Oncologico Ematologico Subalpino (COES), University of Turin, 10126 Torino, Italy
7
Cittá della salute e della scienza University Hospital of Turin, University of Turin, 10126 Torino, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(3), 746; https://doi.org/10.3390/cancers12030746
Submission received: 27 February 2020 / Revised: 14 March 2020 / Accepted: 18 March 2020 / Published: 21 March 2020
(This article belongs to the Special Issue The Cancer Proteome)
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Abstract

Pancreatic Ductal Adenocarcinoma (PDA) is an aggressive malignancy with a very poor outcome. Although chemotherapy (CT) treatment has poor efficacy, it can enhance tumor immunogenicity. Tumor-Associated Antigens (TAA) are self-proteins that are overexpressed in tumors that may induce antibody production and can be PDA theranostic targets. However, the prognostic value of TAA-antibody association as Circulating Immune Complexes (CIC) has not yet been elucidated, mainly due to the lack of techniques that lead to their identification. In this study, we show a novel method to separate IgG, IgM, and IgA CIC from sera to use them as prognostic biomarkers of CT response. The PDA Immune-Complexome (IC) was identified using a LTQ-Orbitrap mass spectrometer followed by computational analysis. The analysis of the IC of 37 PDA patients before and after CT revealed differential associated antigens (DAA) for each immunoglobulin class. Our method identified different PDA-specific CIC in patients that were associated with poor prognosis patients. Finally, CIC levels were significantly modified by CT suggesting that they can be used as effective prognostic biomarkers to follow CT response in PDA patients.
Keywords: proteomics; pancreatic cancer; chemotherapy; immune complexes; biomarkers; TAA; computational analysis proteomics; pancreatic cancer; chemotherapy; immune complexes; biomarkers; TAA; computational analysis

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MDPI and ACS Style

Mandili, G.; Follia, L.; Ferrero, G.; Katayama, H.; Hong, W.; Momin, A.A.; Capello, M.; Giordano, D.; Spadi, R.; Satolli, M.A.; et al. Immune-Complexome Analysis Identifies Immunoglobulin-Bound Biomarkers That Predict the Response to Chemotherapy of Pancreatic Cancer Patients. Cancers 2020, 12, 746. https://doi.org/10.3390/cancers12030746

AMA Style

Mandili G, Follia L, Ferrero G, Katayama H, Hong W, Momin AA, Capello M, Giordano D, Spadi R, Satolli MA, et al. Immune-Complexome Analysis Identifies Immunoglobulin-Bound Biomarkers That Predict the Response to Chemotherapy of Pancreatic Cancer Patients. Cancers. 2020; 12(3):746. https://doi.org/10.3390/cancers12030746

Chicago/Turabian Style

Mandili, Giorgia, Laura Follia, Giulio Ferrero, Hiroyuki Katayama, Wang Hong, Amin A. Momin, Michela Capello, Daniele Giordano, Rosella Spadi, Maria Antonietta Satolli, and et al. 2020. "Immune-Complexome Analysis Identifies Immunoglobulin-Bound Biomarkers That Predict the Response to Chemotherapy of Pancreatic Cancer Patients" Cancers 12, no. 3: 746. https://doi.org/10.3390/cancers12030746

APA Style

Mandili, G., Follia, L., Ferrero, G., Katayama, H., Hong, W., Momin, A. A., Capello, M., Giordano, D., Spadi, R., Satolli, M. A., Evangelista, A., Hanash, S. M., Cordero, F., & Novelli, F. (2020). Immune-Complexome Analysis Identifies Immunoglobulin-Bound Biomarkers That Predict the Response to Chemotherapy of Pancreatic Cancer Patients. Cancers, 12(3), 746. https://doi.org/10.3390/cancers12030746

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