Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.
Background
The superior mesenteric artery-first approach has been proved superior in pancreatoduodenectomy compared with the standard procedure. It is unclear whether similar benefits could be obtained in distal pancreatectomy with celiac axis resection.
Methods
Perioperative and survival outcomes of patients who underwent distal pancreatectomy with celiac axis resection with the modified artery-first approach or traditional approach between January 2012 and September 2021 were compared.
Results
The entire cohort comprised 106 patients (modified artery-first approach, n = 35; traditional approach, n = 71). The most common complication was postoperative pancreatic fistula (n = 18, 17.0 per cent), followed by ischaemic complications (n = 17, 16.0 per cent) and surgical site infection (n = 15, 14.0 per cent). Intraoperative blood loss (400 versus 600 ml, P = 0.017) and intraoperative transfusion rate (8.6 versus 29.6 per cent, P = 0.015) were lower in the modified artery-first approach group compared with the traditional approach group. A higher number of harvested lymph nodes (18 versus 13, P = 0.030) and R0 resection rate (88.6 versus 70.4 per cent, P = 0.038) and a lower incidence of ischaemic complications (5.7 versus 21.1 per cent, P = 0.042) was observed in the modified artery-first approach group compared with the traditional approach group. In multivariable analysis, the modified artery-first approach (OR 0.006, 95 per cent c.i., 0 to 0.447; P = 0.020) was protective against ischaemic complications.
Conclusions
Compared with the traditional approach, the modified artery-first approach was associated with lower blood loss and fewer ischaemic complications, and a higher number of harvested lymph nodes and R0 resection rate. Thus, it might improve the safety, staging and prognosis of distal pancreatectomy with celiac axis resection for pancreatic cancer.
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