Somatostatin Analogs Treated Small Intestinal Neuroendocrine Tumor Patients Circulating MicroRNAs.
We previously detected and investigated nine altered microRNAs in small intestinal neuroendocrine tumor (SI-NET) tissues at different stages of disease. The aims of this study are to: 1) analyze whether SI-NET tissue microRNAs can be also detected in patient serum samples, 2) investigate a potential somatostatin analogs (SSAs) role on microRNA levels regulation in SSA-treated patient samples and 3) elucidate whether the serum microRNA levels in samples collected in different hospitals are predictable and steady. Our results show that tissue microRNAs are detectable in patient serum samples, and miR-96, -182, -183, -196a and -200a levels are lower in SI-NET untreated patients than in SSA-treated patients at all different stages. Conversely, miR-31, -129-5p, -133a and -215 levels do not show any difference in untreated SI-NET patients and SSA-treated patients at all different stages. Our findings also show that miR-200a exhibits an atypical behavior with high levels in both untreated and SSA-treated patients at liver metastasis stage, and unequivocally never at the earlier stages. Serum samples collected in two hospitals keep alike microRNA level pattern, elucidating that the results are not dependent on samples handling. In conclusion, SI-NET tissue microRNAs are always detectable in untreated and SSA-treated patient serum samples, SSAs play an unknown role in eliciting SSA-treated patients' microRNA levels higher than in untreated patients, and this study enlightens that miR-200a might be involved in the liver metastasis during SI-NET progression.
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Su-Chen
SC
Li
Neuroendocrine Tumor Unit, Centre for Gastroenterology, Royal Free Hospital, London, United Kingdom; The Royal Marsden NHS Foundation Trust, London, United Kingdom.
Mohid
M
Khan
Neuroendocrine Tumor Unit, Centre for Gastroenterology, Royal Free Hospital, London, United Kingdom.
Martyn
M
Caplin
Department of Oncology, UCL Cancer Institute, University College London, London, United Kingdom.
Tim
T
Meyer
Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Endocrine Oncology Clinic, Uppsala University Hospital, Science for Life Laboratory, Uppsala, Sweden.
Kjell
K
Öberg
Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Endocrine Oncology Clinic, Uppsala University Hospital, Science for Life Laboratory, Uppsala, Sweden.
Valeria
V
Giandomenico
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007414:Intestinal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use*
D014408:Biomarkers, Tumor; D035683:MicroRNAs; D013004:Somatostatin