Oncotarget

Research Papers:

Proteomic profiling of antibody-inducing immunogens in tumor tissue identifies PSMA1, LAP3, ANXA3, and maspin as colon cancer markers

Qian Yang, Michael H. Roehrl _ and Julia Y. Wang

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Oncotarget. 2018; 9:3996-4019. https://doi.org/10.18632/oncotarget.23583

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Abstract

Qian Yang1,2, Michael H. Roehrl1,2,3 and Julia Y. Wang1,2,4

1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

2Ontario Cancer Institute, University Health Network, Toronto, Canada

3Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

4Curandis, Boston, MA, USA

Correspondence to:

Michael H. Roehrl, email: roehrlm@mskcc.org

Julia Y. Wang, email: julia@wangresearchlab.org

Keywords: colon cancer; antibody; immunogen; precision diagnostics; immunotherapy

Abbreviations: ANXA3: annexin A3; IHC: immunohistochemistry; LAP3: leucine aminopeptidase 3; MS: mass spectrometry; PSMA1: proteasome subunit alpha type-1

Received: June 05, 2017     Accepted: June 27, 2017     Published: December 22, 2017

ABSTRACT

We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer.

Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry.

170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases.

These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins.


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