Juntendo University, Japan
Title: ERC/mesothelin as a biomarker for mesothelioma and gastrointestinal cancer
Biography: Tomoaki Ito
Previously, we found that the ERC (Expressed in Renal Carcinoma) gene was preferentially expressed in renal cancers in the Eker rat. Furthermore, we subsequently confirmed that ERC is a homolog of the human mesothelin gene, a gene that is strongly expressed in normal mesothelial cells, mesotheliomas, and non-mucinous ovarian carcinomas. The ERC/mesothelin gene (MSLN) encodes a 71 kDa precursor protein, which is cleaved to yield 31 kDa N-terminal (N-ERC/mesothelin) and 40 kDa C-terminal (C-ERC/mesothelin) proteins. N-ERC/mesothelin (also known as megakaryocyte-potentiating factor; MPF) is a soluble protein and is released into the extracellular space and blood. C-ERC/mesothelin is a glycoprotein that is tethered to the cell surface by a glycosylphosphatidylinositol anchor. C-ERC/mesothelin expression of tumor by immunohistochemistry can be correlated with patient’s survival in several human cancers. Soluble mesothelin-related peptide (SMRP) has proven to be a promising biomarker in the sera of patients with mesothelioma and ovarian cancer. As for secreted N-ERC/mesothelin, we previously devised a novel enzyme-linked immunosorbent assay (ELISA) system for determining its concentration in serum and showed that it is useful for diagnosing human mesothelioma and ovarian cancer. In addition, we demonstrated that C-ERC/mesothelin was expressed in gastric cancer and pancreatic cancer tissues. Meanwhile, increased serum N-ERC/mesothelin concentrations are not specific to these patients with gastric cancer or pancreatic cancer. Although N-ERC/mesothelin is established as a reliable marker for mesothelioma, N-ERC/mesothelin is not useful as a diagnostic marker of gastric cancer and pancreatic cancer.