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

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
• mucin
• antigenic targets
• immunotherapy

Article highlights

• Previous reports from clinical trials involving therapeutic agents in solid tumors have indicated that a minimum expression of 50% for antigenic targets is necessary to observe any clinical response.

• In our previous report, we bioinformatically emphasized the potential of MUC3A as a target for immunotherapy in gastric adenocarcinoma, albeit relying on transcriptomic data. Hence, it is reasonable to evaluate the protein expression of MUC3A on tumor cells (IHC approach) in order to make predictions about the efficacy of future immunotherapies.

• More than 50% of the patients exhibited MUC3A expression levels higher than 50 and 70% in PT and MT, respectively. The expression levels were significantly higher in the third and fourth quartiles of the samples, with the fourth quartile showing fluctuations between 85% and 100% in PT sites, and 90% to 100% in MT sites. Notably, there was a positive association between MUC3A expression in PT and MT sites, and higher MUC3A expression was correlated with higher survival rates.

• Based on our prior bioinformatics data suggesting the suitability of MUC3A for immunotherapy in gastric adenocarcinoma, coupled with recent findings showing consistent high expression of MUC3A on gastric tumor cells, we strongly encourage the scientific community to advance their exploration of the experimental aspects related to anti-MUC3A immunotherapy. Furthermore, the correlation between better survival rates and higher expression of MUC3A in gastric adenocarcinoma may support the concept that immunotherapy against MUC3A aligns with the patients’ native immune response.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contributions

MS, NS, and MN designed the study; MS and BS performed the IHC evaluations; RS performed the statistical data analyses; VM, VH, and MN prepared the manuscript.

Acknowledgments

We deeply thank patients and their families who participated in this research with no expectations.

Ethics approval

This study was performed after the approval of Institutional Review Board of Tehran University of Medical Sciences (approval ID: IR.TUMS.DDRI.REC.1397.017).

Consent to participate

Informed consent was obtained from all patients at the time of surgery for the use of their paraffin-embedded tissue blocks in research after finalizing their diagnostic procedure.

Availability of data and materials

All the data analyzed in this study are included in this published manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14728222.2023.2293764

Additional information

Funding

This project was funded by Tehran University of Medical Sciences, Digestive Disease Research Institute (ID: 40230-37-03-97).