Can we predict long-term survival in resectable pancreatic ductal adenocarcinoma?
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Tamara M.H. Gall1, Gareth Gerrard2,3, Adam E. Frampton1, Leandro Castellano1, Raida Ahmad4, Nagy Habib1, Duncan Spalding1, Madhava Pai1, Letizia Foroni4 and Long R. Jiao1
1Department of Surgery and Cancer, Imperial College, Hammersmith Hospital Campus, London W12 0HS, United Kingdom
2Faculty of Medicine, Imperial College, Hammersmith Hospital Campus, London W12 0HS, United Kingdom
3Current address: Sarah Cannon Molecular Diagnostics, HCA Healthcare UK, London WC1E 6JA, United Kingdom
4Department of Histopathology, Imperial College, Hammersmith Hospital Campus, London W12 0HS, United Kingdom
Long R. Jiao, email: [email protected]
Keywords: PDAC; ion torrent; next-generation sequencing; nanostring; cell-free DNA
Received: December 02, 2018 Accepted: December 12, 2018 Published: January 22, 2019
Objective: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumour associated with poor 5-year survival. We aimed to determine factors which differentiate short and long-term survivors and identify a prognostic biomarker.
Methods: Over a ten-year period, patients with resected PDAC who developed disease recurrence within 12 months (Group I) and those who had no disease recurrence for 24 months (Group II) were identified. Clinicopathological data was analysed. Ion Torrent high-throughput sequencing on DNA extracted from FFPE tumour samples was used to identify mutations. Additionally, peripheral blood samples were analysed for variants in cell-free DNA, circulating tumour cells (CTCs), and microRNAs.
Results: Multivariable analysis of clinicopathological factors showed that a positive medial resection margin was significantly associated with short disease-free survival (p = 0.007). Group I patients (n = 21) had a higher frequency of the KRAS mutant mean variant allele (16.93% ± 11.04) compared to those in Group II (n = 13; 7.55% ± 5.76, p = 0.0078). Group I patients also trended towards having a KRAS c.35G>A p.Gly12Asp mutation in addition to variants in other genes, such as TP53, CDKN2A, and SMAD4. Mutational status of cell-free DNA, and number of CTCs, was not found to be useful in this study. A circulating miRNA (hsa-miR-548ah-5p) was found to be significantly differentially expressed.
Conclusions: Medial resection margin status and the frequency of KRAS mutation in the tumour tissue are independent prognostic indicators for resectable PDAC. Circulating miRNA hsa-miR-548ah-5p has the potential to be used as a prognostic biomarker.
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