Expression of the cancer testis antigen IGF2BP3 in colorectal cancers; IGF2BP3 holds promise as a specific immunotherapy target
HMC Shantha Kumara1, Daniel Kirchoff1, Otavia L. Caballero2,5, Tao Su3, Aqeel Ahmed3, Sonali AC. Herath1, Linda Njoh1, Vesna Cekic1, Andrew J. Simpson4,5, Carlos Cordon-Cardo6,7, Richard L. Whelan1,7
1 Division of Colon and Rectal Surgery, Department of Surgery, Mount Sinai Roosevelt Hospital Center, Suite 7B, New York, USA
2 Ludwig Institute for Cancer Research Ltd, New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering, New York, USA
3 Herbert Irving Comprehensive Cancer Center, Columbia University, New York, USA
4 Ludwig Institute for Cancer Research, New York, USA
5 Orygen Biotecnologia S.A., São Paulo, Brazil
6 Department of Pathology, Annenberg Building, New York, USA
7 Icahn School of Medicine at Mount Sinai, New York, USA
Correspondence:
Richard L. Whelan, email:
Keywords: IGF2BP3, colorectal cancer, immunotherapy target
Received: June 16, 2015 Accepted: June 30, 2015 Published: July 1, 2015
Abstract
Introduction: IGF2BP3 (IMP3) is a mRNA binding protein that regulates IGF2 translation and function during embryogenesis. Because IGF2BP3 is undetectable in adult human tissues except the testis, and increased IGF2BP3 expression has been noted in several cancers, it is considered a cancer testis (CT) protein. IGF2BP3 mRNA expression in colorectal cancers (CRC) has not been well studied. This study’s aim was to quantitatively assess IGF2BP3 mRNA expression in CRC and, thus, determine if IGF2BP3 has potential as a vaccine target. Method: Data were collected prospectively from CRC patients in an IRB-approved tissue and data bank. Total RNA was isolated and purified from tumor and normal colonic tissue samples and cDNA synthesized. IGF2BP3 expression was analyzed by quantitative PCR (QPCR). Expression levels of IGF2BP3 in tumors and testis were determined and compared. Tumors with levels greater than 0.1% or more of the testis levels were considered positive. Analysis of IGF2BP3 protein expression by immunohistochemistry (IHC) in tumor and normal tissues was also performed. Results: A total of 84 paired tumor and normal tissue specimens were assessed from patients with Stage 2 and 3 CRC; 43% of tumors had IGF2BP3 mRNA expression levels greater than 0.1 % of that of testis and were considered positive. The median tumor expression level was higher in women (p=0.042). No correlation was found between IGF2BP3 mRNA expression and tumor stage or lymph node involvement. IHC was carried out on paired tumor and normal tissue sections from 46 patients; IGF2BP3 staining was noted in 50% of the tumor sections and in 5% of the normal tissue sections. Discussion: IGF2BP3 mRNA was over expressed in 43% of the tumors whereas the protein was noted in 50% of samples. No correlation between mRNA expression and disease severity was noted. This protein holds promise as a vaccine target, however, a larger study that assesses a more diverse population of patients (Stage 1-4) as well as a study of preoperative serum samples for auto-antibodies to IGF2BP3 are needed to pursue this concept.
