The potential of retinoic acid receptors as prognostic biomarkers and therapeutic targets in gastric cancer.

Autor:	Garattini SK; Department of Oncology, ASUFC University Hospital, Udine, Italy., Basile D; Department of Medical Oncology, San Giovanni di Dio Hospital, Crotone, Italy., De Re V; Immunopathology and Cancer Biomarkers/Bio-Proteomics Facility, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy., Brisotto G; Immunopathology and Cancer Biomarkers/Bio-Proteomics Facility, Centro di Riferimento Oncologico, IRCCS, Aviano, Italy., Miolo G; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy., Canzonieri V; Pathology Unit, IRCCS CRO National Cancer Institute, Aviano, Italy.; Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy., Aprile G; Department of Oncology, University and General Hospital, Udine, Italy.; Department of Oncology, San Bortolo General Hospital, Vicenza, Italy., Corvaja C; Division of Thoracic Oncology, European Institute of Oncology (IEO) IRCCS, Milano, Italy., Buriolla S; Department of Oncology, ASUFC University Hospital, Udine, Italy., Garattini E; Department of Biochemistry and Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy., Puglisi F; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.; Departiment of Medicine, University of Udine, Udine, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Sep 11; Vol. 14, pp. 1453934. Date of Electronic Publication: 2024 Sep 11 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1453934
Abstrakt:	Background: Gastric cancer is a heterogeneous collection of tumors characterized by low survival rates. All-trans retinoic acid (retinoic-acid) is a clinically useful therapeutic agent belonging to the chemical family of retinoids, which consists of both natural and synthetic derivatives of vitamin-A. Retinoids are essential components of the normal diet and they regulate different physiological processes. From a therapeutic point of view, retinoic-acid is the first example of clinically useful differentiating agent. Indeed, the differentiating properties of this compound have promoted the use of retinoic-acid as a standard of care in Acute-Promyelocytic-Leukemia, a rare form of acute myeloid leukemia. In this study, we determine the RNA expression of the six isoforms of Retinoic - Acid - Receptors ( RARα / RARβ / RARγ / RXRα / RXRβ / RXRγ ) in view of their potential use as gastric cancer progression markers and/or therapeutic targets. In addition, we evaluate associations between the expression of these receptors and a simplified molecular classification of stomach tumors as well as the clinical characteristics of the cohort of patients analyzed. Finally, we define the prognostic value of the various Retinoic - Acid - Receptors in gastric cancer. Methods: In this single institution and retrospective RAR-GASTRIC study, we consider 55 consecutive gastric cancer patients. We extract total RNA from the pathological specimens and we perform a NanoString Assay using a customized panel of genes. This allows us to determine the expression levels of the RAR and RXR mRNAs as well as other transcripts of interest. Results: Our data demonstrate ubiquitous expression of the RAR and RXR mRNAs in gastric cancers. High levels of RARα , RARβ , RXRα and RXRβ show a significant association with stage IV tumors, " de novo " metastatic disease, microsatellite-stable-status, epithelial-to-mesenchymal-transition, as well as PIK3CA and TP53 expression. Finally, we observe a worse overall - survival in gastric cancer patients characterized by high RARα / RARβ / RARγ / RXRβ mRNA levels. Conclusions: In gastric cancer, high expression levels of RARα / RARβ / RARγ / RXRβ transcripts are associated with poor clinical and molecular characteristics as well as with reduced overall - survival . Our data are consistent with the idea that RARα , RARβ , RARγ and RXRβ represent potential prognostic markers and therapeutic targets of gastric cancer. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Garattini, Basile, De Re, Brisotto, Miolo, Canzonieri, Aprile, Corvaja, Buriolla, Garattini and Puglisi.)
Databáze:	MEDLINE
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