Decoding the expression pattern of MUC3A in gastric adenocarcinoma: unveiling the key to successful immunotherapy

Expert Opin Ther Targets. 2023 Jul-Dec;27(12):1299-1305. doi: 10.1080/14728222.2023.2293764. Epub 2023 Dec 30.

Abstract

Aims: Despite the promise of immunotherapy for gastric adenocarcinoma, resistance is common, necessitating the validation of new targets. Based on our previous bioinformatics analysis, the MUC3A antigen emerged as a promising candidate for immunotherapy against gastric adenocarcinoma. However, a comprehensive understanding of its expression at protein level remains elusive, despite its crucial role in determining clinical response. We also sought to establish a connection between the expression pattern and relevant clinical variables of the disease, whenever feasible.

Methods: Immunohistochemistry was used to determine the percentage of MUC3A-positive tumor cells in primary (PT) and metastatic tumor (MT) sites of 190 gastric adenocarcinoma patients. We also evaluated the association between MUC3A expression and variables such as Lauren classification, history of neoadjuvant chemotherapy and/or radiotherapy, and overall patient survival.

Results: Median MUC3A expression was 50% in PT and 70% in MT sites, exhibiting a positive correlation. MT intestinal type showed significantly higher MUC3A expression compared to other types. Neoadjuvant therapy history did not affect MUC3A expression. Higher MUC3A expression correlated with improved survival.

Conclusions: Based on our previous bioinformatics data and the consistently high expression of MUC3A on gastric tumor cells, we propose advancing experimental aspects of anti-MUC3A immunotherapy for gastric adenocarcinoma.

Keywords: Gastric adenocarcinoma; MUC3A; antigenic targets; immunotherapy; mucin.

MeSH terms

  • Adenocarcinoma* / therapy
  • Humans
  • Immunotherapy
  • Mucin-3
  • Stomach Neoplasms* / therapy

Substances

  • MUC3A protein, human
  • Mucin-3