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Article

Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis

by
Antonio Doronzo
1,†,
Letizia Porcelli
2,†,
Donatello Marziliano
3,
Gianfranco Inglese
3,
Antonella Argentiero
4,
Amalia Azzariti
2,‡ and
Antonio Giovanni Solimando
3,*,‡
1
U.O.C. Oncologia—Ospedale Mons. R. Dimiccoli, 76121 Barletta, Italy
2
Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
3
Guido Baccelli Unit of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area—(DiMePRe-J), School of Medicine, Aldo Moro University of Bari, 70124 Bari, Italy
4
Medical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Medicina 2023, 59(5), 872; https://doi.org/10.3390/medicina59050872
Submission received: 28 December 2022 / Revised: 23 April 2023 / Accepted: 28 April 2023 / Published: 30 April 2023
(This article belongs to the Section Gastroenterology & Hepatology)
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Abstract

Background: Over the past few decades, there has been much debate and research into the link between alcohol consumption and the development and progression of pancreatic ductal adenocarcinoma (PDAC). Objectives: To contribute to the ongoing discussion and gain further insights into this topic, our study analysed the gene expression differences in PDAC patients based on their alcohol consumption history. Methods: To this end, we interrogated a large publicly available dataset. We next validated our findings in vitro. Results: Our findings revealed that patients with a history of alcohol consumption showed significant enrichment in the TGFβ-pathway: a signaling pathway implicated in cancer development and tumor progression. Specifically, our bioinformatic dissection of gene expression differences in 171 patients with PDAC showed that those who had consumed alcohol had higher levels of TGFβ-related genes. Moreover, we validated the role of the TGFβ pathway as one of the molecular drivers in producing massive stroma, a hallmark feature of PDAC, in patients with a history of alcohol consumption. This suggests that inhibition of the TGFβ pathway could serve as a novel therapeutic target for PDAC patients with a history of alcohol consumption and lead to increased sensitivity to chemotherapy. Our study provides valuable insights into the molecular mechanisms underlying the link between alcohol consumption and PDAC progression. Conclusions: Our findings highlight the potential significance of the TGFβ pathway as a therapeutic target. The development of TGFβ-inhibitors may pave the way for developing more effective treatment strategies for PDAC patients with a history of alcohol consumption.
Keywords: pancreatic cancer; PDAC; history of alcohol; TGFβ; fibrotic stroma pancreatic cancer; PDAC; history of alcohol; TGFβ; fibrotic stroma

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MDPI and ACS Style

Doronzo, A.; Porcelli, L.; Marziliano, D.; Inglese, G.; Argentiero, A.; Azzariti, A.; Solimando, A.G. Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis. Medicina 2023, 59, 872. https://doi.org/10.3390/medicina59050872

AMA Style

Doronzo A, Porcelli L, Marziliano D, Inglese G, Argentiero A, Azzariti A, Solimando AG. Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis. Medicina. 2023; 59(5):872. https://doi.org/10.3390/medicina59050872

Chicago/Turabian Style

Doronzo, Antonio, Letizia Porcelli, Donatello Marziliano, Gianfranco Inglese, Antonella Argentiero, Amalia Azzariti, and Antonio Giovanni Solimando. 2023. "Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis" Medicina 59, no. 5: 872. https://doi.org/10.3390/medicina59050872

APA Style

Doronzo, A., Porcelli, L., Marziliano, D., Inglese, G., Argentiero, A., Azzariti, A., & Solimando, A. G. (2023). Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis. Medicina, 59(5), 872. https://doi.org/10.3390/medicina59050872

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