The cancer testis antigens CABYR-a/b and CABYR-c are expressed in a subset of colorectal cancers and hold promise as targets for specific immunotherapy
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H.M.C. Shantha Kumara1, Elie Sutton2, Otavia L. Caballero3,9, Tao Su4, Xiaohong Yan1, Aqeel Ahmed4, Sonali A.C. Herath5, Vesna Cekic1, Linda Njoh6, Daniel D. Kirchoff7 and Richard L. Whelan1,8
1 Division of Colon and Rectal Surgery, Department of Surgery, Lenox Hill Hospital, Northwell Health, New York, NY 10028, USA
2 Department of Surgery, Mount Sinai West Hospital, New York, NY 10019, USA
3 Ludwig Institute for Cancer Research Ltd., New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering, New York, NY, USA
4 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA
5 University of Vermont Medical Center, Internal Medicine Hospitalist Service, Burlington, VT 05401, USA
6 Department of Mathematics, City University of New York at Lehman College, Bronx, NY 10468, USA
7 Roper St. Francis Physician Partners Surgical Oncology, Charleston, SC 29403, USA
8 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
9 Current address: Orygen Biotecnologia S.A., São Paulo, Brazil
|Richard L. Whelan,||email:||Rwhelan1@northwell.edu|
Keywords: cancer testis antigens; colorectal cancer; CABYR a/b, c
Received: December 08, 2020 Accepted: February 01, 2021 Published: March 02, 2021
Introduction: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is expressed in the human germ line but not in adult human tissues, thus, it is considered a cancer testis protein. The aim of this study is to evaluate the CABYR isoforms: a/b and c mRNA expression in colorectal cancer (CRC) and to determine if these proteins hold promise as vaccine targets.
Materials and Methods: CABYR mRNA expression in a set of normal human tissues, including the testis, were determined and compared using semi-quantitative PCR. As regards the tumor and normal mucosal samples from study patients, RNA was extracted and cDNA generated after which quantitative PCR was carried out. Analysis of CABYR protein expressions by immunohistochemistry in tumor and normal colon tissues was also performed.
Results: A total of 47 paired CRC and normal tissue specimens were studied. The percent of patients with a relative expression ratio of malignant to normal (M/N) tissues over 1 was 70% for CABYR a/b and 72% for CABYR c. The percent with both a M/N ratio over 1 and expression levels over 0.1% of testis was 23.4% for CABYR-a/b and 25.5% for CABYR c. CABYR expression in tumors was further confirmed by immunohistochemistry.
Conclusions: CABYR a/b and c hold promise as specific immunotherapy targets, however, a larger and more diverse group of tumors (Stage 1-4) needs to be assessed and evaluation of blood for anti-CABYR antibodies is needed to pursue this concept.
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