Abstract
Pancreatic ductal adenocarcinoma is an aggressive form of pancreatic cancer and the fourth leading cause of cancer-related death. When possible, curative approaches are based on surgical resection, though not every patient is a candidate for surgery. There are clinical guidelines for the management of these patients that offer different treatment options depending on the clinical and pathologic characteristics. However, the survival rates seen in this kind of patients are still low. The CDSE1 gene is located upstream of NRAS and encodes an RNA-binding protein termed UNR. The aim of this study was to analyze UNR expression and its correlation with outcome in patients with resectable pancreatic ductal adenocarcinoma (PDAC). For this, samples from resectable PDAC patients who underwent duodenopancreatectomy were used to evaluate UNR protein expression by immunohistochemistry using a tissue microarray. Here, we observed that low UNR expression was significantly associated with shorter progression-free survival after surgery (P = 0.010). Moreover, this prognostic marker remained significant after Cox proportional hazards model (P = 0.036). We further studied the role of CDSE1 expression in patient’s prognosis using data from public repositories (GEO and TGCA), confirming our results. Interestingly, CDSE1 expression correlated with that of genes characteristic of an immunogenic molecular subtype of pancreatic cancer. Based on these findings, UNR may be considered a potential prognostic biomarker for resectable PDAC and may serve to guide subsequent adjuvant treatment decisions.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) has higher incidence in industrialised countries [1] and is the fourth leading cause of cancer death in both sexes in the USA, where 53,070 new cases of PDAC were diagnosed in 2016 [2]
Preoperative levels of carbohydrate antigen 19–9 (CA 19–9) are the only prognostic biomarker approved by the Food and Drug Administration (FDA) for use in cases of resectable PDAC [12]
We find a direct correlation between CSDE1 and NRAS messenger RNA (mRNA) levels in PDAC samples from the TGCA database
Summary
Pancreatic ductal adenocarcinoma (PDAC) has higher incidence in industrialised countries [1] and is the fourth leading cause of cancer death in both sexes in the USA, where 53,070 new cases of PDAC were diagnosed in 2016 [2]. Preoperative levels of carbohydrate antigen 19–9 (CA 19–9) are the only prognostic biomarker approved by the Food and Drug Administration (FDA) for use in cases of resectable PDAC [12]. This marker shows a relatively high sensitivity and specificity for PDAC [13], providing results that are superior to those of other markers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 50 (CA-50), and DUPAN-2 [14, 15]. The applicability of CA 19–9 is compromised by the fact that biliary obstruction can increase its serum levels [16], and up to 10% of the population cannot synthesise this antigen [17]
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