Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alteration
The incidence and mortality of pancreatic adenocarcinoma (PC) are expected to increase in the coming years, with survival rates remaining poor due to limited treatment options. KRAS mutations, present in over 70% of PC cases, drive aggressive tumor behavior through metabolic reprogramming and immune...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1613773/full |
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| author | Giuseppe Defazio Federico Scolari Sara Fancelli Simone Polvani Daniele Lavacchi Lucia Picariello Alessandro Tubita Michaela Luconi Lorenzo Antonuzzo Lorenzo Antonuzzo Andrea Galli Serena Pillozzi |
| author_facet | Giuseppe Defazio Federico Scolari Sara Fancelli Simone Polvani Daniele Lavacchi Lucia Picariello Alessandro Tubita Michaela Luconi Lorenzo Antonuzzo Lorenzo Antonuzzo Andrea Galli Serena Pillozzi |
| author_sort | Giuseppe Defazio |
| collection | DOAJ |
| description | The incidence and mortality of pancreatic adenocarcinoma (PC) are expected to increase in the coming years, with survival rates remaining poor due to limited treatment options. KRAS mutations, present in over 70% of PC cases, drive aggressive tumor behavior through metabolic reprogramming and immune evasion; however, clinically effective inhibitors for the most common mutations are still lacking. In this study, we analyzed RNA sequencing data from TCGA datasets, comparing tumor versus normal pancreatic tissues and stratifying samples based on KRAS mutation status. Our findings reveal significant dysregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in PC, particularly in the context of KRAS mutations. These findings were validated through RT-qPCR in an independent cohort of primary samples. Key genes, including CD36, FABP4, PLIN1, PLIN4, SCD5, and ACSLs, were consistently downregulated in tumor tissues, with further reductions observed in KRAS-mutated samples. Overall, this study highlights the critical role of PPAR pathway disruption in KRAS-mutated PC, which should be further addressed to improve current treatment strategies. |
| format | Article |
| id | doaj-art-a0b5c3b0fb5341f9adf4cb349966a736 |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-a0b5c3b0fb5341f9adf4cb349966a7362025-08-20T02:58:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16137731613773Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alterationGiuseppe Defazio0Federico Scolari1Sara Fancelli2Simone Polvani3Daniele Lavacchi4Lucia Picariello5Alessandro Tubita6Michaela Luconi7Lorenzo Antonuzzo8Lorenzo Antonuzzo9Andrea Galli10Serena Pillozzi11Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyClinical Oncology Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyThe incidence and mortality of pancreatic adenocarcinoma (PC) are expected to increase in the coming years, with survival rates remaining poor due to limited treatment options. KRAS mutations, present in over 70% of PC cases, drive aggressive tumor behavior through metabolic reprogramming and immune evasion; however, clinically effective inhibitors for the most common mutations are still lacking. In this study, we analyzed RNA sequencing data from TCGA datasets, comparing tumor versus normal pancreatic tissues and stratifying samples based on KRAS mutation status. Our findings reveal significant dysregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in PC, particularly in the context of KRAS mutations. These findings were validated through RT-qPCR in an independent cohort of primary samples. Key genes, including CD36, FABP4, PLIN1, PLIN4, SCD5, and ACSLs, were consistently downregulated in tumor tissues, with further reductions observed in KRAS-mutated samples. Overall, this study highlights the critical role of PPAR pathway disruption in KRAS-mutated PC, which should be further addressed to improve current treatment strategies.https://www.frontiersin.org/articles/10.3389/fonc.2025.1613773/fullpancreatic cancerKRAS mutationsPPAR signaling pathwaytranscriptomic analysislipid metabolismmolecular profiling |
| spellingShingle | Giuseppe Defazio Federico Scolari Sara Fancelli Simone Polvani Daniele Lavacchi Lucia Picariello Alessandro Tubita Michaela Luconi Lorenzo Antonuzzo Lorenzo Antonuzzo Andrea Galli Serena Pillozzi Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alteration Frontiers in Oncology pancreatic cancer KRAS mutations PPAR signaling pathway transcriptomic analysis lipid metabolism molecular profiling |
| title | Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alteration |
| title_full | Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alteration |
| title_fullStr | Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alteration |
| title_full_unstemmed | Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alteration |
| title_short | Transcriptomic analysis on pancreatic adenocarcinoma patients uncovers KRAS-mediated PPAR pathway alteration |
| title_sort | transcriptomic analysis on pancreatic adenocarcinoma patients uncovers kras mediated ppar pathway alteration |
| topic | pancreatic cancer KRAS mutations PPAR signaling pathway transcriptomic analysis lipid metabolism molecular profiling |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1613773/full |
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