Abstract
BackgroundThe aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers.MethodsExpression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n = 165), ampullary cancer (n=59), duodenal cancer (n = 6), distal common bile duct cancer (n = 21), and gastric cancer (n = 20); chronic pancreatitis (n = 39); and normal pancreas (n = 35). The microRNAs were analyzed by PCR using the Fluidigm platform.ResultsTwenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, −23a-3p, −31-5p, −34c-5p, −93-3p, −135b-3p, −155-5p, −186-5p, −196b-5p, −203, −205-5p, −210, −222-3p, −451, −492, −614, and miR-622) and 5 were downregulated (miR-122-5p, −130b-3p, −216b, −217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, −34a-5p, −125a-3p, −146a-5p, −187, −205-5p, −212-3p, −222-5p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices).ConclusionThe study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer.
Highlights
The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers
Pancreatic cancer (PC) located in the head of the pancreas constitutes the majority (60–70%) of the group of cancers in the region, which includes of ampullary adenocarcinomas (A-AC), accounting for 15–25%; and duodenal cancers (DC); and distal common bile duct (CBD) cancers, each accounting for approximately 10%[6]
The computer-generated index II performed in the same way with regard to PC vs. healthy subjects (HS), but was inferior for separating the other malignancies from HS except for distal CBD cancer, where it performed better than index I
Summary
The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers. Pancreatic cancer (PC) is the fourth most common cause of cancer-related death in the Western world, it only represents 3% of all new cancer cases [1, 2]. Due to locally advanced or metastatic disease, only 20% of PC located in the head of the pancreas constitutes the majority (60–70%) of the group of cancers in the region, which includes of ampullary adenocarcinomas (A-AC), accounting for 15–25%; and duodenal cancers (DC); and distal common bile duct (CBD) cancers, each accounting for approximately 10%[6]. Cancer antigen 19–9 (CA 19–9, named carbohydrate antigen 19–9 and sialylated Lewis antigen) is the most widely used biomarker for patients with PC. There is an obvious need for better biomarkers in PC, and microRNAs (miRNAs, miRs) could be interesting in this regard
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