Whole‐transcriptome sequencing analyses identified exosomal circular RNAs in the plasma of pancreatic cancer patients as novel blood‐based biomarkers of disease

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Abstract Pancreatic cancer (PaCa) patients have a low rate of curative resection and a high frequency of relapse. Exosomes from plasma can carry molecules such as proteins, DNAs, mRNAs, and noncoding RNAs; among these molecules, those that are differentially expressed may be novel diagnostic biomarkers for PaCa. To obtain PaCa‐associated exosomal RNA signatures, we employed whole‐transcriptome sequencing of plasma exosomes from PaCa patients and found that a total of 1522 mRNAs and 23 circular RNAs (circRNAs) were differentially expressed in plasma exosomes from PaCa patients. Five circRNAs (hsa_circ_0000690, hsa_circ_0002130, hsa_circ_0037096, hsa_circ_0000976, and hsa_circ_0001821) were overexpressed, which was consistent with the expression levels of their host genes (integrin subunit alpha L [ITGAL], complement C3 [C3], proprotein convertase subtilisin/kexin type 6 [PCSK6], hippocalcin‐like 1 [HPCAL1], and Pvt1 oncogene (nonprotein coding) [PVT1]) in the plasma exosomes from PaCa patients. Furthermore, hsa_circ_0000976, hsa_circ_0002130, and hsa_circ_0037096 were verified to be highly expressed in the plasma of PaCa patients by qRT‐PCR analyses. The areas under the curve (AUCs) of hsa_circ_0000976, hsa_circ_0002130, hsa_circ_0037096, and carbohydrate antigen 19‐9 (CA19‐9) were 0.851, 0.675, 0.696, and 0.843, respectively, and the combination of hsa_circ_0000976 with CA19‐9 significantly increased the AUC to 0.914. Collectively, our findings underscore that hsa_circ_0000976, hsa_circ_0002130, and hsa_circ_0037096 can serve as novel biomarkers and potential therapeutic targets for PaCa and that differential circRNAs may present an enormous opportunity in PaCa diagnostics.

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