IMP3 overexpression occurs in various important cancer types and is linked to aggressive tumor features: A tissue microarray study on 8,877 human cancers and normal tissues

Abstract

IMP3 is an RNA binding protein required for ribosomal RNA processing, which has been suggested to be a prognostic marker in a large variety of human types of cancer. However, available data on the prevalence of IMP3 expression are largely discrepant. To systematically investigate the epidemiology and clinical relevance of IMP3 expression in human cancers we employed a two-step tissue microarrays (TMAs) approach. First, a normal tissue TMA and a multi-tumor TMA were analyzed for immunohistochemically detectable expression of IMP3 in 76 different normal tissue types and 3889 cancer samples from 95 different tumor categories. In a second step, we searched for associations between IMP3 expression and tumor phenotype and patient prognosis in TMAs containing 697 urinary bladder cancers, 1711 colon cancers, 343 esophageal adenocarcinomas, 251 esophageal squamous cell cancers, 673 lung cancers), 275 pancreatic cancers and 230 stomach cancers. In normal tissues, unequivocal IMP3 expression was found in placenta, lymphocytes and some types of glandular epithelial cells. In cancers, at least one case with weak expression could be found in 76 out of 95 (80%) different tumor types and 64 entities (67%) had at least one tumor with strong positivity. IMP3 expression was most frequently found in testicular cancer (including 71% seminomas and 96% non-seminomas), neuroblastoma (88%), and squamous cell cancer of various origins. Significant associations were found between IMP3 and adverse tumor features in esophageal adenocarcinomas and cancers of the urinary bladder, lung, stomach, and pancreas. In summary, IMP3 was frequently expressed in many different tumor types, and was typically associated with aggressive tumor features.

Overexpression of IGF2BP3 as a Potential Oncogene in Ovarian Clear Cell Carcinoma

“…The siRNA effect will diminish after a few days so that we believe that the reduced tumor size was due to a transient inhibition, which amounted to a delayed start in tumor growth. Further, we reported another mechanism by which IGF2BP3 knockdown reduced the MMP2 and MMP9 protein levels in OCCC, as shown in triple negative breast cancer before (20). Because IGF2BP3 is able to bind multiple target RNAs, thereby altering their stability, translatability and/or localization, we predict that it may function directly or indirectly to modify the expression of the various gene products, including MMPs, PCNA or other proteins involved in the control of cell proliferation, death, migration and invasion as shown in this study.…”

“…IGF2BP3 has been reported to be involved in the progression of various cancers, including those in the pancreas (11), colon or rectum (17), lungs (18), and ovaries (19). According to a study with microarray assays of 8,877 human cancers and normal tissues, IGF2BP3 is associated with aggressive tumor features and unfavorable outcomes (20). In lung adenocarcinoma, overexpression of IGF2BP3 may induce the proliferation of cancer cells by mRNA degradation (21).…”

Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma

“…The upregulated RBPs were remarkably enriched in ncRNA processing, tRNA metabolic process, cytoplasmic ribonucleoprotein granule, RNA transport, spliceosome, and mRNA surveillance pathway. Burdelski et al had previously reported the role of RNA processing in various cancer types [36]. In some cases, tumors utilize the mRNA surveillance pathway to downregulate gene expression by destroying key tumor-suppressor mRNAs, whereas in other cases, tumors adapt to their microenvironment by regulating the activity of mRNA surveillance pathway [37].…”

Circulating and tissue IMP3 levels are correlated with poor survival in renal cell carcinoma

“…IMP3 (Insulin‐like growth factor mRNA‐binding protein 3) is a member of the IMP family and has shown to be expressed at low or undetectable protein levels in normal adult tissues . In contrast, in several malignant tumors IMP3 protein expression is strongly up‐regulated . Furthermore, IMP3 protein expression has been identified as an independent prognostic factor in a series of tumors such as oral, breast, colorectal and bladder cancer .…”