Abstract 423A: A tumor-associated mRNA localizing in circulating exosomes as a novel serological marker for pancreatic cancer: the retrospective clinical study

Abstract

Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in the Western world. Early diagnosis of PDAC is difficult, and no biomarkers in blood can identify patients with pancreatic cancer at an early stage. Serum cancer antigen 19-9 (CA19-9) remains the gold standard serum marker for patients with PDAC; however, inadequate sensitivity and specificity limit the use of CA19-9 in the early diagnosis of PDAC. Therefore, the discovery of biomarkers derived from blood that facilitate the distinction of PDAC would greatly affect patient management. Exosomes are extracellular lipid microvesicles, secreted by nearly all cells in body fluids such as peripheral blood. The exosome-associated RNA is called exosomal shuttle RNA that includes microRNAs and messenger RNAs (mRNAs). Methods: The aims of the present study are to assess if the mRNA that we found in the intracellular exosomes of PDAC cells is secreted from PDAC cells, and it is useful as a serum diagnostic marker for differentiating PDAC from individuals without pancreatic disorders compared with CA19-9. 20 PDAC patients (stage III: n = 5, stage IVa: n = 7 and stage IVb: n = 8 according to the classification of pancreatic carcinoma of the Japan Pancreas Society) and 30 control individuals without pancreatic diseases were analyzed in a retrospective cohort study. Circulating exosomes were isolated from serum, and then the mRNA localizing in exosomes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results: We confirmed that the mRNA was localized in secreted exosomes from cultured PDAC cells: a moderately differentiated PDAC cell line (S2-013) by the use of condition media real-time RT-PCR. Furthermore, the retrospective clinical study showed that the area under the curve (AUC) of reciever operating characteristic curves (ROC curves) was 0.805 (95%CI 0.691-0.9199) for this RNA and 0.8 (95%CI 0.675-0.926) for CA19-9. If the mRNA was combined with serum CA19-9, the AUC increased (0.921 [95%CI 0.851-0.991]). Conclusions: Our data suggest that measuring the level of this exosome-associated mRNA has the potential to improve detection of PDAC. Further research is necessary to understand whether this mRNA has clinical implications for early detection of PDAC (stage I and II) and how much this information adds to serum CA19-9. Citation Format: Keisuke Taniuchi. A tumor-associated mRNA localizing in circulating exosomes as a novel serological marker for pancreatic cancer: the retrospective clinical study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 423A.