miR-1246 and miR-4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer

Abstract

Pancreatobiliary tract cancer is a highly fatal cancer. Detection of pancreatobiliary tract cancer is difficult because it lacks typical clinical symptoms and because of its anatomical location. Biomarker discovery is therefore important to detect pancreatobiliary tract cancer in its early stage. A study demonstrated that expression levels of miR‑1246, miR‑3976, miR‑4306, and miR‑4644 in serum exosomes were higher in pancreatic cancer patients than these levels in healthy control participants. Supposing that microRNA (miRNA) expression profiles in saliva are similar to those in serum, four miRNAs (miR‑1246, miR‑3976, miR‑4306, and miR‑4644) in salivary exosomes may also be useful for detection of pancreatobiliary tract cancer. In this study, it was examined whether these miRNAs could be used as biomarkers for pancreatobiliary tract cancer. Twelve pancreatobiliary tract cancer patients and 13 healthy control participants were analyzed as a cancer and a control group, respectively. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. Using quantitative real‑time PCR (RT‑qPCR), the relative expression ratios of miR‑1246 and miR‑4644 were significantly higher in the cancer group than these ratios in the control group. Receiver operating characteristic (ROC) curves were constructed to analyze the discrimination power of these miRNAs. For miR‑1246, the results yielded an area under the curve (AUC) of 0.814 (P=0.008). For miR‑4644, the results yielded an AUC of 0.763 (P=0.026). For the combination of miR‑1246 and miR‑4644, the results yielded an increased AUC of 0.833 (P=0.005). This pilot study suggests that miR‑1246 and miR‑4644 in salivary exosomes could be candidate biomarkers for pancreatobiliary tract cancer.

Salivary MicroRNA for Diagnosis of Cancer and Systemic Diseases: A Systematic Review

“…Eleven papers eventually fulfilled the inclusion and exclusion criteria. Table 2 shows the selected papers and their general characteristics such as title, authors, year of publication, disease investigated, selected biomarkers, analytical techniques used, and type of saliva collected [10][11][12][13][14][15][16][17][18][19][20].…”

“…Four studies investigated pancreatic oncological diseases. Specifically, paper 3 investigated the presence of two specific miRNAs in salivary exosomes, through a comparison between pancreatic-biliary tract cancer patients and HC [12].…”

“…Overall, 18 salivary miRNAs (miR-1246, miR-4644, miR-21, miR-34a, mir-155, miR-200b, miR-376a, miR-23a, miR-23b, miR-29c, miR-210, miR-216, miR-940, miR-3679-5p, miR-17, miR-18b, miR-18a, and miR-196a), detected through targeted and untargeted methods, have been studied in relation to the presence of pancreatic cancer, irrespective of the stage of development of the tumor [12][13][14][15]18].…”

A Novel Saliva-Based miRNA Signature for Colorectal Cancer Diagnosis

“…For instance, Xie et al identified a model composed by miR-3679-5p and miR-940 with 72.5% sensitivity and 70% specificity for differentiating pancreatic cancer patients from controls [19]. Further, in pancreatic cancer, the combination of miR-1246 and miR-4644 yielded 83.3% sensitivity and 92.3% specificity for this tumor diagnosis [20]. These findings demonstrate the potential of saliva as a source of biomarkers for non-oral cancers detection.…”

Research Progress on Exosomes Derived from Human Adipose Mesenchymal Stem Cells

“…Therefore, most cells can release exosomes. The exosomes can also be separated from human body's natural body fluids, such as urine 36 , plasma 37 ,breast milk 38 , saliva 39 , ascites 40 , etc.The exosome is formed by endocytosis. First, the plasma membrane recesses inward to form an endosomes body and encapsulates the contents.…”