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ANTXR1 (TEM8) overexpression in gastric adenocarcinoma makes the protein a potential target of immunotherapy

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Abstract

Background

Despite the promise of immunotherapy for gastric adenocarcinoma, choices for the selection of effective antigenic targets are very limited. Previously published data and our own in-house computational analysis have suggested that ANTXR1 is a potential target, simultaneously expressed in malignant tumor cells and the endothelial cells of the tumors. However, the expression pattern of ANTXR1 protein in clinical samples of gastric adenocarcinoma has not been fully evaluated.

Methods

Using immunohistochemistry (IHC), we recorded the percentage of ANTXR1 positive cells separately in tumor cells and endothelial cells in the primary tumor, non-tumor gastric tissue adjacent to the primary tumor, and tumor in metastatic sites of 140 gastric adenocarcinoma patients. We also evaluated the association of ANTXR1 expression with the Lauren histological classification of the primary tumors, the patient’s history of neoadjuvant chemotherapy and/or radiotherapy, and the patient’s overall survival.

Results

ANTXR1 was expressed in a mean of 73.89 ± 30.12% of tumor cells and 13.55 ± 20.53% of endothelial cells in the primary tumors. Intestinal adenocarcinomas had lower ANTXR1 expression in the tumor cells and higher ANTXR1 expression in the endothelial cells of the tumor regions, and a history of neoadjuvant therapy was associated with increased ANTXR1 expression in the endothelial cells of the tumor regions. Finally, above median expression of ANTXR1 in the tumor cells of the tumor regions was associated with significantly lower overall patient survival.

Conclusions

Our findings suggest that ANTXR1 is a promising candidate for preclinical and clinical evaluation for gastric adenocarcinoma immunotherapy.

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Abbreviations

ANTXR1:

ANTXR cell adhesion molecule 1

CAR T cell:

Chimeric antigen receptor T cells

ERBB2:

Erb-b2 receptor tyrosine kinase 2

KDR:

Kinase insert domain receptor

MT:

Metastatic tumor

NT:

Non-tumor region

PDCD1:

Programmed cell death 1

PDX:

Patient-derived xenograft

PT:

Primary tumor

TMA:

Tissue microarray

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Funding

This project was funded by Tehran University of Medical Sciences, Digestive Disease Research Institute grant number 38435-37-02-97.

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Authors and Affiliations

  1. Digestive Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Masoud Sotoudeh

  2. Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Ramin Shakeri

  3. Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

    Sanford M. Dawsey

  4. Department of Genetics, Colleague of Science, Kazerun Branch, Islamic Azad University, Kazerun, Iran

    Bahareh Sharififard

  5. Cell-Based Therapies Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Shariati Hospital, P.O. Box 14117-13135, Tehran, Iran

    Naser Ahmadbeigi & Mahmood Naderi

Authors
  1. Masoud Sotoudeh
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  2. Ramin Shakeri
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  3. Sanford M. Dawsey
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  4. Bahareh Sharififard
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  5. Naser Ahmadbeigi
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  6. Mahmood Naderi
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Contributions

MS, NA, and MN designed the study; MS and BS performed the IHC evaluations; RS performed the statistical data analyses; and MN and SMD prepared the manuscript.

Corresponding author

Correspondence to Mahmood Naderi.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

This study was performed after the approval of Institutional Review Board of Tehran University of Medical Sciences (approval ID: IR.TUMS.DDRI.REC.1397.007).

Informed consent

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.

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Sotoudeh, M., Shakeri, R., Dawsey, S.M. et al. ANTXR1 (TEM8) overexpression in gastric adenocarcinoma makes the protein a potential target of immunotherapy. Cancer Immunol Immunother 68, 1597–1603 (2019). https://doi.org/10.1007/s00262-019-02392-y

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  • DOI: https://doi.org/10.1007/s00262-019-02392-y

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