Clinical significance of exosomes as potential biomarkers in cancer

BACKGROUND Exosomes are microvesicles, measuring 30-100 nm in diameter. They are widely distributed in body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, proteins and lipids, and may serve as novel biomarkers in cancer.AIM To summarize the performance of exosomal biomarkers in cancer diagnosis and prognosis.METHODS Relevant publications in the literature were identified by search of the "PubMed"database up to September 11, 2018. The quality of the included studies was assessed by QUADAS-2 and REMARK. For assessment of diagnostic biomarkers,47 biomarkers and 2240 patients from 30 studies were included.RESULTS Our results suggested that these exosomal biomarkers had excellent diagnostic ability in various types of cancer, with good sensitivity and specificity. For assessment of prognostic markers, 50 biomarkers and 4797 patients from 42 studies were included. We observed that exosomal biomarkers had prognostic values in overall survival, disease-free survival and recurrence-free survival.CONCLUSION Exosomes can function as potential biomarkers in cancer diagnosis and prognosis.

Therapeutic potential of targeting acinar cell reprogramming in pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRasG12 D mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinarto-ductal-metaplasia(ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia(Pan IN) and eventually PDAC. During ADM, the activation of mitogen-activated protein kinases, Wnt, Notch and phosphatidylinositide 3-kinases/Akt signaling inhibits the transcription of acinar-specific genes, including Mist and amylase, but promotes the expression of ductal genes, such as cytokeratin-19. Inhibition of this transdifferentiation process hinders the development of Pan IN and PDAC. In addition, the transdifferentiated cells regain acinar identity, indicating ADM may be a reversible process. This provides a new therapeutic direction in treating PDAC through cancer reprogramming. Many studies have already demonstrated the success of switching Pan IN/PDAC back to normal cells through the use of PD325901, the expression of E47, and the knockdown of Dickkopf-3. In this review, we discuss the signaling pathways involved in ADM and the therapeutic potential of targeting reprogramming in order to treat PDAC.