Circulating Exosomal MicroRNA Of Oesophageal Adenocarcinoma Patients

Background: Oesophageal carcinoma is one of the most common diseasesof oesophagus, and is also the major human malignancy. It’s the sixth leadingcause of death in the world.Major pathohistology subtypes of oesophageal cancerare oesophageal squamous cell carcinoma (OSCC) and oesophagealadenocarcinoma (OAC). OSCC is predominantly found in Asian countries. Fromnorthern Iran through Central Asia to North-Central China, which is referred to asthe “Asian belt”, the incidence of OSCC is over100per100,000. In westerncountries, although OSCC is still the major pathohistology subtype ofoesophageal carcinoma; OAC morbidity keeps growing in recent years. In somecountries like Denmark and Scotland, the morbidity of OAC has exceeded that ofOSCC. In China, a morbidity trend similar to Western countries has beenobserved, that the number of OAC patients increases, as a result of bettereconomic status, changes in diet and increase of obesity. The importance of earlydiagnosis of oesophageal adenocarcinoma is more urgent. In the research of earlydiagonsis of oesophageal adenocarcinoma, esoxomes attract more attention.Exosomes are a cluster of nano particles released by cells. Initially they werefound in sheep reticulocytes, and later discovered in almost every kind of cells.Exosomes bear a range of components derived from host cells, such as proteins,lipids and RNAs. These components could be delivered to recipient cells byexosomes and play important roles in the recipient’s cells functions. In recentyears, exosomes miRNA as biomarkers for tumours has been studied intensively.MicroRNAs from cancer-patient-derived exosomes have shown its potential in arange of tumours such as lung cancer and ovarian cancer. Those findings indicatethat exosomes miRNA from cancer patients could be a group of promising cancerbiomarkers, and might contribute to early diagnosis of cancer.Methods: Ten OAC patients and ten non-cancer subjects were involved inthis study. As a strong male bias is observed in oesophageal adenocarcinoma, only male patients were included in our study. Written consents were obtained fromeach patient/subject. Blood of patients/subjects was collected and plasma andserum were isolated to eluminate noisy signals from some complex bloodcomponents. Exosomes were pelleted from each serum and plasma sample, andexosomal miRNAs were extracted. Expression levels of exosomal miRNA wereprofiled using OpenArray real-time PCR system and data were analysed by astatistical software package Statminer, GraphPad Prism and Microsoft Excel.Results: Data analysis showed that10serum exosomal miRNAs weredifferentially expressed between OAC and non-cancer people with P value lessthan0.05: hsa-miR-a，hsa-miR-b，hsa-miR-c，hsa-miR-d，hsa-miR-e，hsa-miR-f，hsa-miR-g，h，hsa-miR-i，hsa-miR-j. In plasma,16exosomal miRNAs weredifferentially expressed between OAC and non-cancer people with P value lessthan0.05: k，l，hsa-miR-m，hsa-miR-n，hsa-miR-o，hsa-miR-p，hsa-miR-q，hsa-miR-r，hsa-miR-s，hsa-miR-t，hsa-miR-u，hsa-miR-v，hsa-miR-w，x，hsa-miR-i，hsa-mR-j. IPA showed that these significant miRNAs were activelyinvolved in physiological functions and cellular functions highly related to cancer,like tumour morphology, cell proliferation and apoptosis, cellular movement, cellcycles and gastrointestinal disease, etc.Conclusions: Exosomal miRNAs from OAC patients may contribute to thescreening and early diagnosis of OAC.