Laura L Meijer1, Ingrid Garajová2,3, Chiara Caparello4, Tessa Y S Le Large1,2,5, Adam E Frampton6, Enrico Vasile4, Niccola Funel7, Geert Kazemier1, Elisa Giovannetti2,7. 1. Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU University Amsterdam, the Netherlands. 2. Department of Medical Oncology, Cancer Center Amsterdam, VU University Amsterdam, The Netherlands. 3. Department of Medical Oncology, University Hospital S. Orsola-Malpighi, Bologna, Italy. 4. Department of Medical Oncology, University Hospital of Pisa, Pisa, Italy. 5. Laboratory of Experimental Oncology & Radiobiology, Academic Medical Center, Amsterdam, The Netherlands. 6. HPB Surgical Unit, Department of Surgery & Cancer, Imperial College, London, United Kingdom. 7. Cancer Pharmacology Lab, AIRC-Start-Up Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University Hospital of Pisa, Pisa, Italy.
Abstract
OBJECTIVE: The aim of the study was to identify plasma microRNA (miRNA) biomarkers for stratifying and monitoring patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX, and to investigate their functional roles. SUMMARY BACKGROUND DATA: FOLFIRINOX has become a standard therapy for patients with advanced PDAC and can be used to potentially downstage disease. However, only a subset of patients respond, and biomarkers to guide decision-making are urgently needed. METHODS: We used microarray-based profiling to discover deregulated miRNAs in pre- and postchemotherapy plasma samples from patients based on their progression-free survival (PFS) after FOLFIRINOX. Nine candidate plasma miRNAs were validated in an independent cohort (n = 43). The most discriminative plasma miRNA was correlated with clinicopathological factors and survival, and also investigated in an additional cohort treated with gemcitabine plus nab-paclitaxel. Expression patterns were further evaluated in matched tumor tissues. In vitro studies explored its function, key downstream gene-targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. RESULTS: Plasma miR-181a-5p was significantly downregulated in non-progressive patients after FOLFIRINOX. In multivariate analysis, this decline correlated with improved PFS and overall survival, especially when combined with CA19-9 decline [hazard ratio (HR) = 0.153, 95% confidence interval (CI), 0.067-0.347 and HR = 0.201, 95% CI, 0.070-0.576, respectively]. This combination did not correlate with survival in patients treated with gemcitabine plus nab-paclitaxel. Tissue expression of miR-181a-5p reflected plasma levels. Inhibition of miR-181a-5p coupled with oxaliplatin exposure in pancreatic cell lines decreased cell viability. CONCLUSIONS: Plasma miR-181a-5p is a specific biomarker for monitoring FOLFIRINOX response. Decline in plasma miR-181a-5p and CA19-9 levels is associated with better prognosis after FOLFIRINOX and may be useful for guiding therapeutic choices and surgical exploration.
OBJECTIVE: The aim of the study was to identify plasma microRNA (miRNA) biomarkers for stratifying and monitoring patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX, and to investigate their functional roles. SUMMARY BACKGROUND DATA: FOLFIRINOX has become a standard therapy for patients with advanced PDAC and can be used to potentially downstage disease. However, only a subset of patients respond, and biomarkers to guide decision-making are urgently needed. METHODS: We used microarray-based profiling to discover deregulated miRNAs in pre- and postchemotherapy plasma samples from patients based on their progression-free survival (PFS) after FOLFIRINOX. Nine candidate plasma miRNAs were validated in an independent cohort (n = 43). The most discriminative plasma miRNA was correlated with clinicopathological factors and survival, and also investigated in an additional cohort treated with gemcitabine plus nab-paclitaxel. Expression patterns were further evaluated in matched tumor tissues. In vitro studies explored its function, key downstream gene-targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. RESULTS: Plasma miR-181a-5p was significantly downregulated in non-progressive patients after FOLFIRINOX. In multivariate analysis, this decline correlated with improved PFS and overall survival, especially when combined with CA19-9 decline [hazard ratio (HR) = 0.153, 95% confidence interval (CI), 0.067-0.347 and HR = 0.201, 95% CI, 0.070-0.576, respectively]. This combination did not correlate with survival in patients treated with gemcitabine plus nab-paclitaxel. Tissue expression of miR-181a-5p reflected plasma levels. Inhibition of miR-181a-5p coupled with oxaliplatin exposure in pancreatic cell lines decreased cell viability. CONCLUSIONS: Plasma miR-181a-5p is a specific biomarker for monitoring FOLFIRINOX response. Decline in plasma miR-181a-5p and CA19-9 levels is associated with better prognosis after FOLFIRINOX and may be useful for guiding therapeutic choices and surgical exploration.
Authors: Olivia D Lara; Ying Wang; Amma Asare; Tao Xu; Hua-Sheng Chiu; Yuexin Liu; Wei Hu; Pavel Sumazin; Shitanshu Uppal; Lin Zhang; J Alejandro Rauh-Hain; Anil K Sood Journal: Cancer Date: 2019-11-15 Impact factor: 6.860
Authors: Elena Fernandez-Castañer; Maria Vila-Casadesus; Elena Vila-Navarro; Carolina Parra; Juan Jose Lozano; Antoni Castells; Meritxell Gironella Journal: Cancers (Basel) Date: 2021-05-14 Impact factor: 6.639
Authors: Emanuela Dell'Aquila; Claudia Angela Maria Fulgenzi; Alessandro Minelli; Fabrizio Citarella; Marco Stellato; Francesco Pantano; Marco Russano; Maria Concetta Cursano; Andrea Napolitano; Tea Zeppola; Bruno Vincenzi; Giuseppe Tonini; Daniele Santini Journal: Oncotarget Date: 2020-03-10