P2RX7B is a new theranostic marker for lung adenocarcinoma patients

Benzaquen, Jonathan; Dit Hreich, Serena Janho; Heeke, Simon; Juhel, Thierry; Lalvee, Salomé; Bauwens, Serge; Saccani, Simona; Lenormand, Philippe; Hofman, Véronique; Butori, Mathilde; Leroy, Sylvie; Berthet, Jean-Philippe; Marquette, Charles-Hugo; Hofman, Paul; Vouret-Craviari, Valérie

doi:10.7150/thno.48229

Nanotheranostics

International Journal of Biological Sciences

International Journal of Medical Sciences

Journal of Cancer

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Theranostics 2020; 10(24):10849-10860. doi:10.7150/thno.48229 This issue Cite

Research Paper

P2RX7B is a new theranostic marker for lung adenocarcinoma patients

Jonathan Benzaquen^1,4,5,6, Serena Janho Dit Hreich^1,5, Simon Heeke^1,2, Thierry Juhel^1,5, Salomé Lalvee^2,3, Serge Bauwens¹, Simona Saccani¹, Philippe Lenormand¹, Véronique Hofman^1,2,3,4, Mathilde Butori¹, Sylvie Leroy^4,6,7, Jean-Philippe Berthet⁸, Charles-Hugo Marquette^1,4,6, Paul Hofman^1,2,3,4, Valérie Vouret-Craviari^1,4,5✉

1. Université Côte d'Azur, CNRS, INSERM, IRCAN UMR 7284, 06108 Nice, France.
2. Laboratory of Clinical and Experimental Pathology and Biobank, Pasteur Hospital, Nice, France.
3. Hospital-Related Biobank (BB-0033-00025), Pasteur Hospital, Nice, France.
4. FHU OncoAge, Nice, France.
5. Centre Antoine Lacassagne, 06107 Nice, France.
6. Department of Pulmonary Medicine and Oncology, Pasteur Hospital, Nice, France.
7. Université Côte d'Azur, CNRS UMR 7275 - IPMC, Sophia Antipolis, France.
8. Department of Thoracic surgery, Pasteur Hospital, Nice, France.

Citation:

Benzaquen J, Dit Hreich SJ, Heeke S, Juhel T, Lalvee S, Bauwens S, Saccani S, Lenormand P, Hofman V, Butori M, Leroy S, Berthet JP, Marquette CH, Hofman P, Vouret-Craviari V. P2RX7B is a new theranostic marker for lung adenocarcinoma patients. Theranostics 2020; 10(24):10849-10860. doi:10.7150/thno.48229. https://www.thno.org/v10p10849.htm

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Abstract

Rationale: The characterization of new theranostic biomarkers is crucial to improving the clinical outcome of patients with advanced lung cancer. Here, we aimed at characterizing the P2RX7 receptor, a positive modulator of the anti-tumor immune response, in patients with lung adenocarcinoma.

Methods: The expression of P2RX7 and its splice variants was analyzed by RT-qPCR using areas of tumor and non-tumor lung adenocarcinoma (LUAD) tissues on both immune and non-immune cells. The biological activity of P2RX7 was studied by flow cytometry using fluorescent dyes. Bi-molecular fluorescence complementation and confocal microscopy were used to assess the oligomerization of P2RX7. Tumor immune infiltrates were characterized by immunohistochemistry.

Results: Fifty-three patients with LUAD were evaluated. P2RX7A, and 3 alternative splice variants were expressed in LUAD tissues and expression was down regulated in tumor versus adjacent non-tumor tissues. The protein retained biological activity only in immune cells. The P2RX7B splice variant was differentially upregulated in immune cells (P < 0.001) of the tumor and strong evidence of oligomerization of P2RX7A and B was observed in the HEK expression model, which correlated with a default in the activity of P2RX7. Finally, LUAD patients with a high level of P2RX7B had non-inflamed tumors (P = 0.001).

Conclusion: Our findings identified P2RX7B as a new theranostic tool to restore functional P2RX7 activity and open alternative therapeutic opportunities to improve LUAD patient outcome.

Keywords: lung cancer, P2X7R, purinergic signaling, ATP, splice variant

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APA

Benzaquen, J., Dit Hreich, S.J., Heeke, S., Juhel, T., Lalvee, S., Bauwens, S., Saccani, S., Lenormand, P., Hofman, V., Butori, M., Leroy, S., Berthet, J.P., Marquette, C.H., Hofman, P., Vouret-Craviari, V. (2020). P2RX7B is a new theranostic marker for lung adenocarcinoma patients. Theranostics, 10(24), 10849-10860. https://doi.org/10.7150/thno.48229.

ACS

Benzaquen, J.; Dit Hreich, S.J.; Heeke, S.; Juhel, T.; Lalvee, S.; Bauwens, S.; Saccani, S.; Lenormand, P.; Hofman, V.; Butori, M.; Leroy, S.; Berthet, J.P.; Marquette, C.H.; Hofman, P.; Vouret-Craviari, V. P2RX7B is a new theranostic marker for lung adenocarcinoma patients. Theranostics 2020, 10 (24), 10849-10860. DOI: 10.7150/thno.48229.

NLM

CSE

Benzaquen J, Dit Hreich SJ, Heeke S, Juhel T, Lalvee S, Bauwens S, Saccani S, Lenormand P, Hofman V, Butori M, Leroy S, Berthet JP, Marquette CH, Hofman P, Vouret-Craviari V. 2020. P2RX7B is a new theranostic marker for lung adenocarcinoma patients. Theranostics. 10(24):10849-10860.

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