Open AccessCirculating pancreatic cancer exosomal RNA s for detection of pancreatic cancer
Author(s) -
Kitagawa Tatsuya,
Taniuchi Keisuke,
Tsuboi Makiko,
Sakaguchi Masahiko,
Kohsaki Takuhiro,
Okabayashi Takehiro,
Saibara Toshiji
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12398
Subject(s) - pancreatic cancer , messenger rna , rna , biomarker , medicine , ca19 9 , microrna , cancer , cancer research , real time polymerase chain reaction , reverse transcription polymerase chain reaction , area under the curve , microvesicles , pancreas , pathology , biology , gene , biochemistry
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 RNA s ( mRNA s: CCDC 88A , ARF 6 , Vav3 , and WASF 2 ) and five small nucleolar RNA s (sno RNA s: SNORA 14B , SNORA 18 , SNORA 25 , SNORA 74A , and SNORD 22 ) 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 CA 19‐9, the standard clinical tumor biomarker. Reverse transcription quantitative real‐time PCR showed that all of the mRNA s and sno RNA s, except CCDC 88A , 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 mRNA s ( WASF 2 and ARF 6 ) and two sno RNA s ( SNORA 74A and SNORA 25 ) was > 0.9 for distinguishing pancreatic cancer patients from controls; the AUC of CA 19‐9 was 0.897. Comparing serum levels of WASF 2 , ARF 6 , SNORA 74A , SNORA 25 , and CA 19‐9 revealed that levels of WASF 2 were the most highly correlated with the risk of pancreatic cancer. The AUC s of WASF 2 , ARF 6 , SNORA 74A , and SNORA 25 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 CA 19‐9. The results of this study suggest that WASF 2 , ARF 6 , SNORA 74A , and SNORA 25 may be useful tools for the early detection of pancreatic cancer. Monitoring serum levels of WASF 2 mRNA may be particularly useful, as it was the most highly correlated with pancreatic cancer risk.