The putative pleiotropic functions of meprin β in gastric cancer.

Abstract

BACKGROUND:

The gastric microbiome and inflammation play a key role in gastric cancer (GC) by regulating the immune response in a complex manner and by inflammatory events supporting carcinogenesis. Meprin β is a zinc endopeptidase and participates in tissue homeostasis, intestinal barrier function and immunological processes. It influences local inflammatory processes, dysbiosis and the microbiome. Here, we tested the hypothesis that meprin β is expressed in GC and of tumor biological significance.

PATIENTS AND METHODS:

Four hundred forty whole mount tissue sections of patients with therapy-naive GC were stained with an anti-meprin β antibody. The histoscore and staining pattern were analyzed for each case. Following dichotomization at the median histoscore into a "low" and "high" group, the expression was correlated with numerous clinicopathological patient characteristics.

RESULTS:

Meprin β was found intracellularly and at the cell membrane of GC. Cytoplasmic expression correlated with the phenotype according to Lauren, microsatellite instability and PD-L1 status. Membranous expression correlated with intestinal phenotype, mucin-1-, E-cadherin-, β-catenin status, mucin typus, microsatellite instability, KRAS mutation and PD-L1-positivity. Patients with cytoplasmic expression of meprin β showed a better overall and tumor-specific survival.

CONCLUSIONS:

Meprin β is differentially expressed in GC and has potential tumor biological relevance. It might function as a tumor suppressor or promotor depending on histoanatomical site and context.

• Authors: Wiebke Siemsen, Christine Halske, Hans-Michael Behrens, Sandra Krüger, Christoph Becker-Pauly, Christoph Röcken
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 26 Issue 4 Pg. 542-552 (07 2023) ISSN: 1436-3305 [Electronic] Japan
• PMID: 36976399 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• B7-H1 Antigen
• Mucins

Topics

• Humans
• B7-H1 Antigen (genetics)
• Stomach Neoplasms (pathology)
• Microsatellite Instability
• Mucins (genetics)
• Cell Membrane (metabolism)