Abstract
BackgroundPancreatic ductal adenocarcinoma (PDAC) remains a dismal disease, with very little improvement in survival over the past 50 years. Recent large-scale genomic studies have improved understanding of the genomic and transcriptomic landscape of the disease, yet very little is known about molecular heterogeneity according to tumour location in the pancreas; body and tail PDACs especially tend to have a significantly worse prognosis. The aim was to investigate the molecular differences between PDAC of the head and those of the body and tail of the pancreas.MethodsDetailed correlative analysis of clinicopathological variables, including tumour location, genomic and transcriptomic data, was performed using the Australian Pancreatic Cancer Genome Initiative (APGI) cohort, part of the International Cancer Genome Consortium study.ResultsClinicopathological data were available for 518 patients recruited to the APGI, of whom 421 underwent genomic analyses; 179 of these patients underwent whole-genome and 96 RNA sequencing. Patients with tumours of the body and tail had significantly worse survival than those with pancreatic head tumours (12·1 versus 22·0 months; P = 0·001). Location in the body and tail was associated with the squamous subtype of PDAC. Body and tail PDACs enriched for gene programmes involved in tumour invasion and epithelial-to-mesenchymal transition, as well as features of poor antitumour immune response. Whether this is due to a molecular predisposition from the outset, or reflects a later time point on the tumour molecular clock, requires further investigation using well designed prospective studies in pancreatic cancer.ConclusionPDACs of the body and tail demonstrate aggressive tumour biology that may explain worse clinical outcomes.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is expected to become the third leading cause of cancer-related death in Western societies, and to overtake breast cancer for the first time in 20171
The present study has demonstrated distinct molecular differences between resectable PDAC from the head and body/tail
Body and tail pancreatic cancer is associated with the squamous subtype of pancreatic cancer and enriched for gene programmes associated with inflammation, epithelial-tomesenchymal transition (EMT) and potential immune avoidance mechanisms
Summary
Pancreatic ductal adenocarcinoma (PDAC) is expected to become the third leading cause of cancer-related death in Western societies, and to overtake breast cancer for the first time in 20171. Numerous studies[5,6,7,8,9] have demonstrated meaningful differences in outcome of pancreatic cancers located in the head, compared with those of the body and tail. Recent large-scale genomic studies have improved understanding of the genomic and transcriptomic landscape of the disease, yet very little is known about molecular heterogeneity according to tumour location in the pancreas; body and tail PDACs especially tend to have a significantly worse prognosis. Body and tail PDACs enriched for gene programmes involved in tumour invasion and epithelial-to-mesenchymal transition, as well as features of poor antitumour immune response Whether this is due to a molecular predisposition from the outset, or reflects a later time point on the tumour molecular clock, requires further investigation using well designed prospective studies in pancreatic cancer. Conclusion: PDACs of the body and tail demonstrate aggressive tumour biology that may explain worse clinical outcomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
