Exosomal miR-1290 is a potential biomarker of high-grade serous ovarian carcinoma and can discriminate patients from those with malignancies of other histological types
Tóm tắt
microRNAs (miRNAs) stably exist in circulating blood encapsulated in extracellular vesicles such as exosomes; therefore, serum miRNAs have the potential to serve as novel cancer biomarkers. New diagnostic markers to detect high grade serous ovarian cancer (HGSOC) are urgently needed. The aim of this study was to identify miRNAs specific to HGSOC and analyze whether serum miRNA can discriminate HGSOC patients from healthy controls or patients with ovarian malignancies of other histological types. Exosomes from ovarian cancer cell lines were collected and exosomal miRNAs extracted. miRNA microarray analysis revealed several elevated miRNAs specific to HGSOC. Among these, we focused on miR-1290. Sera from 70 ovarian cancer patients and 13 healthy controls were gathered and its expression levels detected by quantitative real-time polymerase chain reaction. In HGSOC patients, serum miR-1290 was significantly overexpressed compared to in healthy controls (3.52 fold; P = 0.03), unlike in patients with ovarian cancers of other histological types. The relative expression of miR-1290 was higher in advanced stages of HGSOC than in early stages (4.23 vs. 1.58; P = 0.23). Its expression significantly decreased after operation (5.87 to 1.17; P < 0.01), indicating that this miRNA reflects tumor burden. A receiver operating characteristic curve analysis showed that at the cut-off of 1.20, the sensitivity and specificity were 63% and 85% respectively for discriminating patients with HGSOC (area under the curve [AUC] = 0.71) from healthy controls, and at the cut-off of 1.55, the sensitivity and specificity were 47% and 85% respectively for discriminating patients with HGSOC (AUC = 0.76) from those with malignancies of other histological types. Serum miR-1290 is significantly elevated in patients with HGSOC and can be used to discriminate these patients from those with malignancies of other histological types; it is a new potential diagnostic biomarker for HGSOC.
Tài liệu tham khảo
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.
Cohen M, Petignat P. Purified autoantibodies against glucose-regulated protein 78 (GRP78) promote apoptosis and decrease invasiveness of ovarian cancer cells. Cancer Lett. 2011;309:104–9.
NIH Surveillance, Epidemiology, and End Results Program Database. http://seer.cancer.gov/statfacts/html/ovary.html. Updated November, 2017.
Badgwell D, Bast RC Jr. Early detection of ovarian cancer. Dis Markers 2007;23:397–410.
Montagnana M, Benati M, Danese E. Circulating biomarkers in epithelial ovarian cancer diagnosis: from present to future perspective. Ann Transl Med. 2017;5:276.
Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008;108:402–8.
Leung F, Bernardini MQ, Brown MD, Zheng Y, Molina R, Bast RC Jr, et al. Validation of a novel biomarker panel for the detection of ovarian Cancer. Cancer Epidemiol Biomark Prev. 2016;25:1333–40.
Montagnana M, Lippi G, Ruzzenente O, Bresciani V, Danese E, Scevarolli S, et al. The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass. J Clin Lab Anal. 2009;23:331–5.
Jacobs IJ, Menon U, Ryan A, Gentry-Maharaj A, Burnell M, Kalsi JK, et al. Ovarian cancer screening and mortality in the UK collaborative trial of ovarian Cancer screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387:945–56.
Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513–8.
Lötvall J, Hill AF, Hochberg F, Buzás EI, Di Vizio D, Gardiner C, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles. 2014;3:26913.
Nakamura K, Sawada K, Yoshimura A, Kinose Y, Nakatsuka E, Kimura T. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer. 2016;15:48.
Miyanishi M, Mandai M, Matsumura N, Yamaguchi K, Hamanishi J, Higuchi T, et al. Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression. Oncol Rep. 2007;17:329–33.
Nakamura K, Sawada K, Kinose Y, Yoshimura A, Toda A, Nakatsuka E, et al. Exosomes promote ovarian cancer cell invasion through transfer of CD44 to peritoneal mesothelial cells. Mol Cancer Res. 2017;15:78–92.
Lässer C, Eldh M, Lötvall J. Isolation and characterization of RNA-containing exosomes. J Vis Exp. 2012;59:e3037.
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.
Onda T, Satoh T, Saito T, Kasamatsu T, Nakanishi T, Nakamura K, et al. Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan clinical oncology group study JCOG0602. Eur J Cancer. 2016;64:22–31.
Morice P, Dubernard G, Rey A, Atallah D, Pautier P, Pomel C, et al. Results of interval debulking surgery compared with primary debulking surgery in advanced stage ovarian cancer. J Am Coll Surg. 2003;197:955–63.
Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363:943–53.
Tian C, Markman M, Zaino R, Ozols RF, McGuire WP, Muggia FM, et al. CA-125 change after chemotherapy in prediction of treatment outcome among advanced mucinous and clear cell epithelial ovarian cancers: a gynecologic oncology group study. Cancer. 2009;115:1395–403.
Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L, Sena-Esteves M, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10:1470–6.
Mo D, Gu B, Gong X, Wu L, Wang H, Jiang Y, et al. miR-1290 is a potential prognostic biomarker in non-small cell lung cancer. J Thorac Dis. 2015;7:1570–9.
Li A, Yu J, Kim H, Wolfgang CL, Canto MI, Hruban RH, et al. MicroRNA array analysis finds elevated serum miR-1290 accurately distinguishes patients with low-stage pancreatic cancer from healthy and disease controls. Clin Cancer Res. 2013;19:3600–10.
Wu J, Ji X, Zhu L, Jiang Q, Wen Z, Xu S, et al. Up-regulation of microRNA-1290 impairs cytokinesis and affects the reprogramming of colon cancer cells. Cancer Lett. 2013;329:155–63.
miRTargetLink Human Database. Available at: https://ccb-web.cs.uni-saarland.de/mirtargetlink/ Updated June, 2018.
Wang J, Liao QJ, Zhang Y, Zhou H, Luo CH, Tang J, et al. TRPM7 is required for ovarian cancer cell growth, migration and invasion. Biochem Biophys Res Commun. 2014;454:547–53.
Xu HT, Liu Y, Liu SL, Miao Y, Li QC, Wang EH. TC-1 (C8orf4) expression is correlated with differentiation in ovarian carcinomas and might distinguish metastatic ovarian from metastatic colorectal carcinomas. Virchows Arch. 2013;462:281–7.
Wang B, Li J, Ye Z, Li Z, Wu X. N-myc downstream regulated gene 1 acts as a tumor suppressor in ovarian cancer. Oncol Rep. 2014;31:2279–85.
Hu G, Drescher KM, Chen XM. Exosomal miRNAs: biological properties and therapeutic potential. Front Genet. 2012;3:56.
Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y, Furuta K, et al. Circulating Exosomal microRNAs as biomarkers of Colon Cancer. PLoS One. 2014;9:e92921.
Taylor DD, Gercel-Taylor C. MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 2008;110:13–21.
Yokoi A, Yoshioka Y, Hirakawa A, Yamamoto Y, Ishikawa M, Ikeda S, et al. A combination of circulating miRNAs for the early detection of ovarian cancer. Oncotarget. 2017;8:89811–23.
Shah JS, Gard GB, Yang J, Maidens J, Valmadre S, Soon PS, et al. Combining serum microRNA and CA-125 as prognostic indicators of preoperative surgical outcome in women with high-grade serous ovarian cancer. Gynecol Oncol. 2018;148:181–8.