Abstract
Diagnostic biomarkers for the early diagnosis of pancreatic cancer are needed to improve prognosis for this disease. The aim of this study was to investigate differences in the expression of four messenger RNAs (mRNAs: CCDC88A,ARF6, Vav3, and WASF2) and five small nucleolar RNAs (snoRNAs: SNORA14B,SNORA18,SNORA25,SNORA74A, and SNORD22) in serum of patients with pancreatic cancer and control participants for use in the diagnosis of pancreatic cancer. Results were compared with the expression of sialylated Lewis (a) blood group antigen CA19‐9, the standard clinical tumor biomarker. Reverse transcription quantitative real‐time PCR showed that all of the mRNAs and snoRNAs, except CCDC88A, were encapsulated in exosomes and secreted from cultured pancreatic cancer cells, and present in cell culture medium. In a discovery‐stage clinical study involving 27 pancreatic cancer patients and 13 controls, the area under the receiver operating characteristic curve (AUC) of two mRNAs (WASF2 and ARF6) and two snoRNAs (SNORA74A and SNORA25) was > 0.9 for distinguishing pancreatic cancer patients from controls; the AUC of CA19‐9 was 0.897. Comparing serum levels of WASF2,ARF6,SNORA74A,SNORA25, and CA19‐9 revealed that levels of WASF2 were the most highly correlated with the risk of pancreatic cancer. The AUCs of WASF2,ARF6,SNORA74A, and SNORA25 in serum from patients in the early stages of pancreatic cancer (stages 0, I, and IIA) were > 0.9, compared with an AUC of 0.93 for the level of CA19‐9. The results of this study suggest that WASF2,ARF6,SNORA74A, and SNORA25 may be useful tools for the early detection of pancreatic cancer. Monitoring serum levels of WASF2 mRNA may be particularly useful, as it was the most highly correlated with pancreatic cancer risk.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the Western world (Siegel et al, 2013)
We used RNA fluorescence in situ hybridization to determine the subcellular localization of messenger RNA (mRNA) for CCDC88A, ARF6, Vav3, and WASF2 and small nucleolar RNA (snoRNA) for SNORA14B, SNORA22, SNORA25, SNORA74A, and SNORD22 in moderately differentiated S2-013 PDAC cells
All of these mRNAs and snoRNAs were concentrated in S2-013 cells positive for the cytoplasmic exosome marker CD63 (Fig. 1A)
Summary
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related mortality in the Western world (Siegel et al, 2013). No biomarkers that identify patients with PDAC in the early stages are available (Locker et al, 2006), and the absence of reliable serum biomarkers for PDAC. Abbreviations AUC, area under the receiver operating characteristic curve; CI, confidence interval; lncRNA, long noncoding RNA; mRNA, messenger RNA; OR, odds ratio; PDAC, pancreatic ductal adenocarcinoma; ROC, receiver operating characteristic; snoRNA, small nucleolar RNA. Exosomal RNAs are useful as diagnostic markers reduces the potential effectiveness of screening strategies in at-risk populations, such as patients with diabetes mellitus and chronic pancreatitis. Better diagnostic markers of PDAC could improve the early diagnosis of this disease and enable more patients to undergo curative surgical resection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
