ERC/mesothelin is expressed in human gastric cancer tissues and cell lines

Our plain-English summary of ERC/mesothelin is expressed in human gastric cancer tissues and cell lines, by T. Ito, K. Kajino, M. Abe, et al (Oncology Reports, 2014).

The study

• Authors: T. Ito, K. Kajino, M. Abe, K. Sato, H. Maekawa, M. Sakurada, H. Orita, R. Wada, Y. Kajiyama, O. Hino
• Journal: Oncology Reports
• Published: 2014;31(1):27-33
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

ERC/mesothelin is expressed in mesothelioma and other malignancies. 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 is a soluble protein and has been reported to be a diagnostic serum marker of mesothelioma and ovarian cancer. Gastric cancer tissue also expresses C-ERC/mesothelin, but the significance of serum N-ERC levels for diagnosing gastric cancer has not yet been studied. We examined the latter issue in the present study as well as C-ERC/mesothelin expression in human gastric cancer tissues and cell lines. We immunohistochemically examined C-ERC/mesothelin expression in tissue samples from 50 cases of gastric cancer, and we also assessed the C-ERC/mesothelin expression in 6 gastric cancer cell lines (MKN-1, MKN-7, MKN-74, NUGC-3, NUGC-4 and TMK-1) using reverse transcription-polymerase chain reaction, flow cytometry, immunohistochemistry and immunoblotting. We also examined the N-ERC/mesothelin concentrations in the supernatants of cultured cells and in the sera of gastric cancer patients using an enzyme-linked immunosorbent assay (ELISA). N-ERC/mesothelin was detected in the supernatants of 3 gastric cancer cell lines (MKN-1, NUGC-4 and TMK-1) by ELISA, but its concentration in the sera of gastric cancer patients was almost same as that observed in the sera of the normal controls. In the gastric cancer tissues, C-ERC/mesothelin expression was associated with lymphatic invasion. N-ERC/mesothelin was secreted into the supernatants of gastric cancer cell lines, but does not appear to be a useful serum marker of gastric cancer.

In plain English

This study from Juntendo University in Japan examined whether stomach (gastric) cancer makes a protein called ERC/mesothelin, which the authors had earlier used in a blood test for mesothelioma, and whether its blood level could help diagnose gastric cancer. It did not study asbestos exposure. Five of six gastric cancer cell lines made the protein, at lower levels than a mesothelioma cell line, and three released its soluble form into their culture fluid. In tumor tissue from 50 patients, 29 (58%) stained positive. Staining on the inner (luminal) cell surface was linked to cancer spread into lymphatic vessels (P=0.0286). Blood levels in 38 patients did not differ significantly from those in 37 healthy people of similar age (P=0.3986). An earlier comparison without age-matching showed higher levels in patients, which the authors attributed to the patients being older. The authors concluded that the soluble protein does not appear useful as a blood marker of gastric cancer. They noted the study was small and included no cases of cancer spread to the peritoneum (abdominal lining).

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study of gastric cancer cell lines combined with a hospital study of tumor tissue and blood from gastric cancer patients compared with healthy controls
• Who was studied: 50 gastric cancer patients (40 men and 10 women, aged 33 to 89, mean 71.5) diagnosed between January 2009 and September 2011 at Juntendo Shizuoka Hospital, Japan. The comparison groups were 37 healthy controls in the main blood comparison and 102 healthy controls in an earlier unmatched comparison. The laboratory work used 6 gastric cancer cell lines (MKN-1, MKN-7, MKN-74, NUGC-3, NUGC-4, TMK-1).
• Exposure: No asbestos or other exposure was studied. The study measured the protein ERC/mesothelin: its cell-bound form (C-ERC/mesothelin) in cells and tissue, and its soluble form (N-ERC/mesothelin) in culture fluid and blood.
• Main results:
  • In the cell lines, ERC/mesothelin mRNA and C-ERC protein were detected in 5 of 6 gastric cancer cell lines. NUGC-3 was the exception.
  • Expression levels in the gastric cancer cell lines were lower than in the H226 human mesothelioma cells used as a positive control.
  • By ELISA, 3 cell lines (MKN-1, NUGC-4 and TMK-1) released N-ERC into the culture medium. Western blotting detected it in only 2 (NUGC-4 and TMK-1).
  • In patient tumor tissue, 29 of 50 tumors (58%) were positive for C-ERC/mesothelin. Luminal membrane expression was seen in 15 cases (30%).
  • Overall C-ERC/mesothelin positivity was not associated with any clinicopathological parameter. Luminal membrane expression was correlated with lymphatic invasion (P=0.0286).
  • Serum N-ERC/mesothelin concentrations in 38 age-matched gastric cancer patients did not differ significantly from those in 37 healthy controls (P=0.3986).
  • Among the gastric cancer patients, serum N-ERC/mesothelin concentration did not correlate significantly with TNM stage (P=0.7948).
  • Without age-matching, all 50 patients had significantly higher serum levels than 102 healthy controls (P<0.0001). The authors considered this result biased because the patients tended to be older.
• The authors' conclusion: The authors concluded that N-ERC/mesothelin was secreted by gastric cancer cell lines but does not appear to be useful as a serum marker of gastric cancer.
• Limitations the authors state:
  • The study was small and requires further validation.
  • No cases with spread of cancer cells to the peritoneum were included.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Stomach cancer.

Medical terms in this study, explained in our Lexicon: Mesothelin, Stomach Cancer, Mesothelioma, Ovarian Cancer, Immunohistochemistry.

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