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Correlation between the immune checkpoints and EMT genes proposes potential prognostic and therapeutic targets in ESCC

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Abstract

PD-1, PD-L1, CTLA-4, TIM-3, and LAG-3, crucial immune checkpoint molecules in the tumor microenvironment, identify as key targets for cancer immunotherapy. There is a correlation between immune cells and epithelial-mesenchymal transition (EMT)-related genes expression in varies human cancers. In this study, we aimed to investigate the probable association between expression of immune checkpoints and EMT in esophageal squamous cell carcinoma (ESCC) with clinical treats for providing the new therapeutic targets and prognostic value for the disease. Quantitative real-time PCR was used to investigate the gene expression profile of immune checkpoints (PD-1, PD-L1, CTLA-4, TIM-3, and LAG-3) and EMT (TWIST1 and MMP-13) genes based on the mRNA expression levels in 51 ESCC tissues. The upregulation of CTLA-4, PD-1, PD-L1, TIM-3, LAG-3, MMP-13, and TWIST1 were observed in 31.37%, 29.41%, 21.56%, 39.21%, 25.49%, 60.78%, and 56.86% of ESCC cases at the mRNA level, respectively. Dysregulation of immune checkpoints was related to lymph node involvement, stage of tumor progression, and depth of tumor invasion (P < 0.05). While overexpression of MMP-13 and TWIST1 was associated with lymph node involvement, stage of tumor progression, and grade of tumor differentiation (P < 0.05). The mRNA expression of immune checkpoint genes was significantly correlated to each other's (P = 0.000). Of importance, the data explored the significant association between the concomitant expression of immune checkpoints and EMT-related genes with each other in a variety of clinicopathological traits (P < 0.05). Consequently, immune checkpoints were positively correlated with EMT status in ESCC. The correlation between tumor immune microenvironment with the elevation of multiple immune checkpoints and EMT status may help to identify potential biomarkers for the simultaneous clinical use of multiple immune checkpoints blockade and other immunotherapies approaches for advanced ESCC patients.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors acknowledge the colleagues at the Division of Human Genetics, Avicenna Research Institute, MUMS, for preparing ESCC tissue specimens.

Funding

This study was supported by a Grant from Vice-chancellor of Mashhad University of Medical Sciences (#960741).

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Author notes

  1. Reihaneh Alsadat Mahmoudian and Sahar Mozhgani have contributed equally to this work.

Authors and Affiliations

  1. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Reihaneh Alsadat Mahmoudian, Sahar Mozhgani & Mehran Gholamin

  2. Medical Genetics Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Reza Abbaszadegan

  3. School of Pharmacy, Goethe-University, Frankfurt a. M., Germany

    Leila Mokhlessi

  4. Department of Pathology, Mashhad University of Medical Sciences, Mashhad, Iran

    Mehdi Montazer

  5. Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, P.O.Box, 345-91357, Mashhad, Iran

    Mehran Gholamin

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  1. Reihaneh Alsadat Mahmoudian
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  2. Sahar Mozhgani
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  3. Mohammad Reza Abbaszadegan
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Correspondence to Mehran Gholamin.

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Mahmoudian, R.A., Mozhgani, S., Abbaszadegan, M.R. et al. Correlation between the immune checkpoints and EMT genes proposes potential prognostic and therapeutic targets in ESCC. J Mol Histol 52, 597–609 (2021). https://doi.org/10.1007/s10735-021-09971-3

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