Academic Journal
SALL4‐related gene signature defines a specific stromal subset of pancreatic ductal adenocarcinoma with poor prognostic features
| العنوان: | SALL4‐related gene signature defines a specific stromal subset of pancreatic ductal adenocarcinoma with poor prognostic features |
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| المؤلفون: | Vienot, Angélique, Monnien, Franck, Truntzer, Caroline, Mougey, Virginie, Bouard, Adeline, Pallandre, Jean‐René, Molimard, Chloé, Loyon, Romain, Asgarov, Kamal, Averous, Gerlinde, Ghiringhelli, François, Bibeau, Frédéric, Peixoto, Paul, Borg, Christophe |
| المصدر: | Molecular Oncology ; volume 17, issue 7, page 1356-1378 ; ISSN 1574-7891 1878-0261 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2023 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Pancreatic ductal adenocarcinoma (PDAC) is marked by molecular heterogeneity and poor prognosis. Among the stemness‐related transcription factors, Spalt‐like Transcription Factor 4 (SALL4) is correlated with unfavorable outcomes; however, its roles in PDAC remain unclear. SALL4 high expression defines a PDAC subpopulation characterized by a shortened patient survival. Although SALL4 expression was mostly evaluated in tumor cells, our findings identify this embryonic transcription factor as a new biomarker in PDAC‐derived stroma. Gene expression analysis reveals that the SALL4 high PDAC subset is enriched in cancer stem cell properties and stromal enrichment pathways; notably, an interaction with cancer‐associated fibroblasts (CAF) activated by TGF‐β. A particular oncogenic network was unraveled where Netrin‐1 and TGF‐β1 collaborate to induce SALL4 expression in CAF and drive their cancer‐stemness‐promoting functions. A 7‐gene stromal signature related to SALL4 high PDAC samples was highlighted and validated by immunochemistry for prognosis and clinical application. This SALL4 ‐related stroma discriminated pancreatic preinvasive from invasive lesions and was enriched in short‐term survivors. Our results show that SALL4 transcriptional activity controls a molecular network defined by a specific stromal signature that characterizes PDAC invasiveness and worse clinical outcomes. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/1878-0261.13370 |
| الاتاحة: | http://dx.doi.org/10.1002/1878-0261.13370 https://onlinelibrary.wiley.com/doi/pdf/10.1002/1878-0261.13370 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/1878-0261.13370 https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/1878-0261.13370 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.5A6D4EA |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/1878-0261.13370 |
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