Abstract
Pancreatic cancer is a dismal disease with a mortality rate almost similar to its incidence rate. To date, there are neither validated predictive nor prognostic biomarkers for this lethal disease. Thus, the aim of the present study was to retrospectively investigate the capability of biochemical parameters and molecular profiles to predict survival of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who participated in a phase II clinical trial to test the safety and efficacy of the combination treatment of capecitabine plus nab-paclitaxel. Herein, we investigated the association of 18 biochemical parameters obtained from routine diagnosis and the clinical outcome of the 30 patients enrolled in the clinical trial. Furthermore, we analysed formalin-fixed paraffin-embedded (FFPE) tumour tissue to identify molecular biomarkers via RNA seq and the Illumina TruSeq Amplicon Cancer panel which covers 48 hotspot genes. Our analysis identified SERPINB7 as a novel transcript and a DNA mutation signature that might predict a poor outcome of disease. Moreover, we identified the bilirubin basal level as an independent predictive factor for overall survival in our study cohort.
Highlights
This page was generated automatically upon download from the ETH Zurich Research Collection
The discouraging results from the vast majority of studies focussed on pancreatic cancer might suggest that the gene dysregulation in PDAC might be regulated by other mechanisms, such as epigenetic or post-transcriptional regulation, and we are convinced that finding RNA biomarkers for PDAC could be extremely useful to provide a deeper understanding of PDAC and to advance therapeutic strategies
The results presented are very promising, this study contains three main limitations
Summary
This page was generated automatically upon download from the ETH Zurich Research Collection. In 2012, pancreatic cancer was reported as the seventh most common cause of cancer-related deaths worldwide and according to the Pancreatic Cancer Action Network, it will be the second one by the year 20302, 3 This discouraging prognosis is partly due to the absence of reliable biomarkers and the insufficient understanding of the molecular mechanisms underlying the pathology of pancreatic cancer. In 2013, this phase III clinical trial demonstrated that patients treated with nab-paclitaxel and gemcitabine had a prolonged overall survival (OS) and progression free survival (PFS) in comparison to patients treated with gemcitabine alone[4] These results have prompted several studies exploring nab-paclitaxel in combination with other therapeutic agents to treat pancreatic cancer. Characteristics Age Median, years [range] ≥65 years Sex Female ECOG PS 0 1 Site(s) of metastasis Lung Liver Peritoneum n [%]
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