Expression of the cancer testis antigen IGF2BP3 in colorectal cancers; IGF2BP3 holds promise as a specific immunotherapy target

Abstract

IntroductionIGF2BP3 (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.MethodData 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.ResultsA 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.DiscussionIGF2BP3 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.

IGF2BP3 May Contributes to Lung Tumorigenesis by Regulating the Alternative Splicing of PKM

“…According to previous studies, IGF2BP3 is highly expressed in numerous cancer tissues, such as esophageal cancer, lung cancer, prostate cancer, gastric cancer, and colorectal malignancies ( Shantha Kumara et al, 2015 ; Zhang et al, 2017 ). At the tissue level, previous study has shown IGF2BP3 is higher expressed in squamous cell carcinoma and adenocarcinoma ( Zhao et al, 2017 ).…”

“…Studies showed that IGF2BP3 can induce cell proliferation and invasion through post-transcriptional regulation of IGF2 and promotes lung tumorigenesis via attenuating P53 stability which give us a hint to do more research on it ( Taniuchi et al, 2014 ; Zhao et al, 2017 ). In some cases, overexpression is associated with a worse prognosis or a later stage disease ( Shantha Kumara et al, 2015 ).…”

“…IGF2BP3 (also known as IMP3) is a member of the insulin-like growth factor 2 mRNA binding protein family ( Schmiedel et al, 2016 ). IGF2BP3 is a 580 amino acid protein which has two RNA recognition motifs and four K homology domains, which was encoded by a 4350-bp mRNA transcript generated by the IGF2BP3 gene on chromosome 7p11.5 ( Shantha Kumara et al, 2015 ). RNA binding protein (often abbreviated as RBP), as a crucial molecule, involves in almost all stages of post-transcriptional regulation, thus determining the destiny and function of each transcript in the cell and ensuring cell homeostasis ( Lukong et al, 2008 ; Pereira et al, 2017 ).…”

The RNA binding protein IMP3 facilitates tumor immune escape by downregulating the stress-induced ligands ULPB2 and MICB

“…IMP3 is absent in almost all healthy, adult tissues. However, expression of IMP3 could be observed in several kinds of cancer like in colon carcinoma ( Li et al, 2009 ; Lochhead et al, 2012 ; Kumara et al, 2015 ), adenocarcinomas ( Bellezza et al, 2009 ; Lu et al, 2009 ; Gao et al, 2014 ), urothelial carcinomas ( Sitnikova et al, 2008 ; Xylinas et al, 2014 ), lymphomas ( King et al, 2009 ; Tang et al, 2013 ; Hartmann et al, 2012 ) or renal cell carcinomas ( Hoffmann et al, 2008 ; Jiang et al, 2006 ; Jiang et al, 2008 ).…”

“…Besides the critical role of IMP3 in fetal development ( Mueller-Pillasch et al, 1999 ) and fertility ( Li et al, 2014 ; Hammer et al, 2005 ), its importance as an oncogene in several kinds of cancer was determined in the last few years: Expression of IMP3 could be observed in colon carcinoma ( Li et al, 2009 ; Lochhead et al, 2012 ; Kumara et al, 2015 ), adenocarcinomas ( Bellezza et al, 2009 ; Lu et al, 2009 ; Gao et al, 2014 ), urothelial carcinomas ( Sitnikova et al, 2008 ; Xylinas et al, 2014 ), lymphomas ( King et al, 2009 ; Tang et al, 2013 ; Hartmann et al, 2012 ), renal cell carcinomas ( Hoffmann et al, 2008 ; Jiang et al, 2006 ; 2008 ), and many more ( Hammer et al, 2005 ; Chen et al, 2013 ; Walter et al, 2009 ; Köbel et al, 2009 ; Zhou et al, 2014 ). Additionally, high expression of IMP3 often correlates with poor survival prognosis for patients ( Hoffmann et al, 2008 ; Jiang et al, 2006 ; Köbel et al, 2009 ; Yuan et al, 2009 ; Lin et al, 2013 ).…”