Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis
<i>Background</i>: 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). <i>Objectives</i>: To contribute to the ongoing discussion and gain...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/5/872 |
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| author | Antonio Doronzo Letizia Porcelli Donatello Marziliano Gianfranco Inglese Antonella Argentiero Amalia Azzariti Antonio Giovanni Solimando |
| author_facet | Antonio Doronzo Letizia Porcelli Donatello Marziliano Gianfranco Inglese Antonella Argentiero Amalia Azzariti Antonio Giovanni Solimando |
| author_sort | Antonio Doronzo |
| collection | DOAJ |
| description | <i>Background</i>: 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). <i>Objectives</i>: 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. <i>Methods</i>: To this end, we interrogated a large publicly available dataset. We next validated our findings in vitro. <i>Results</i>: 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. <i>Conclusions</i>: 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. |
| first_indexed | 2024-03-11T03:31:44Z |
| format | Article |
| id | doaj.art-de25d0a1a6ca4c7aa2a222d666c32d5f |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-11T03:31:44Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-de25d0a1a6ca4c7aa2a222d666c32d5f2023-11-18T02:21:29ZengMDPI AGMedicina1010-660X1648-91442023-04-0159587210.3390/medicina59050872Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory AnalysisAntonio Doronzo0Letizia Porcelli1Donatello Marziliano2Gianfranco Inglese3Antonella Argentiero4Amalia Azzariti5Antonio Giovanni Solimando6U.O.C. Oncologia—Ospedale Mons. R. Dimiccoli, 76121 Barletta, ItalyLaboratory of Experimental Pharmacology, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, ItalyGuido 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, ItalyGuido 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, ItalyMedical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, ItalyLaboratory of Experimental Pharmacology, IRCCS Istituto Tumori “Giovanni Paolo II” of Bari, 70124 Bari, ItalyGuido 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<i>Background</i>: 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). <i>Objectives</i>: 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. <i>Methods</i>: To this end, we interrogated a large publicly available dataset. We next validated our findings in vitro. <i>Results</i>: 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. <i>Conclusions</i>: 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.https://www.mdpi.com/1648-9144/59/5/872pancreatic cancerPDAChistory of alcoholTGFβfibrotic stroma |
| spellingShingle | Antonio Doronzo Letizia Porcelli Donatello Marziliano Gianfranco Inglese Antonella Argentiero Amalia Azzariti Antonio Giovanni Solimando Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis Medicina pancreatic cancer PDAC history of alcohol TGFβ fibrotic stroma |
| title | Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis |
| title_full | Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis |
| title_fullStr | Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis |
| title_full_unstemmed | Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis |
| title_short | Gene Expression Comparison between Alcohol-Exposed versus Not Exposed Pancreatic Ductal Adenocarcinoma Patients Reveals a Peculiar TGFβ-Related Phenotype: An Exploratory Analysis |
| title_sort | gene expression comparison between alcohol exposed versus not exposed pancreatic ductal adenocarcinoma patients reveals a peculiar tgfβ related phenotype an exploratory analysis |
| topic | pancreatic cancer PDAC history of alcohol TGFβ fibrotic stroma |
| url | https://www.mdpi.com/1648-9144/59/5/872 |
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