Abstract
Purpose
Exosomes are gradually detected as an indicator for diagnosis and prognosis of breast cancer in clinic and a systematic review was conducted.
Methods
A search for clinical studies published before July 1, 2017 was performed. Methods of exosome purification and identification from all studies were extracted. For diagnosis evaluation, the comparison of exosome biomarkers expression between breast cancer patients and healthy women was obtained; for prognosis prediction, the correlation between exosome biomarkers expression and chemotherapy resistance, overall survival (OS), disease-free survival (DFS), recurrence and metastasis of breast cancer was also extracted.
Results
A total of 11 studies with 921 breast cancer patients were included. Ultracentrifugation is the most frequent method to purify exosomes and transmission electron microscopy is commonly used to identify exosomes. Exosome biomarkers (such as HER2, CD47, Del-1, miR-1246 and miR-21) in breast cancer patients are significantly higher than those in healthy controls, exosomal GSTP1 and TRPC5 are related to chemotherapy resistance, exosome-carrying TRPC5, NANOG, NEUROD1, HTR7, KISS1R and HOXC are correlated to PFS, DFS or OS, and some exosomal proteins (HER2, KDR, CD49d, CXCR4 and CD44) as well as miRNAs (miR-340-5p, miR-17-5p, miR-130a-3p, miR-93-5p) are associated with tumor recurrence or distant organ metastasis.
Conclusions
Exosome biomarkers can be used for early diagnosis and prognosis of breast cancer patients in clinic.
Similar content being viewed by others
References
Harbeck N, Gnant M. Breast cancer. Lancet. 2017;18(389):1134–50. https://doi.org/10.1016/S0140-6736(16)31891-8.
Rugo HS, Olopade OI, DeMichele A, Yau C, van ‘t Veer LJ, Buxton MB, et al. Adaptive randomization of veliparib–carboplatin treatment in breast cancer. N Engl J Med. 2016;375(1):23–34. https://doi.org/10.1056/NEJMoa1513749.
Hannafon BN, Trigoso YD, Calloway CL, Zhao YD, Lum DH, Welm AL, et al. Plasma exosome microRNAs are indicative of breast cancer. Breast Cancer Res. 2016;18(1):90. https://doi.org/10.1186/s13058-016-0753-x.
Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363(20):1938–48. https://doi.org/10.1056/NEJMra1001389.
Hannafon BN, Ding WQ. Intercellular communication by exosome-derived microRNAs in cancer. Int J Mol Sci. 2013;14(7):14240–69. https://doi.org/10.3390/ijms140714240.
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329–35. https://doi.org/10.1038/nature15756.
Donnarumma E, Fiore D, Nappa M, Roscigno G, Adamo A, Iaboni M, et al. Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer. Oncotarget. 2017;8(12):19592–608. https://doi.org/10.18632/oncotarget.14752.
Goodarzi H, Nguyen HC, Zhang S, Dill BD, Molina H, Tavazoie SF. Modulated expression of specific tRNAs drives gene expression and cancer progression. Cell. 2016;165(6):1416–27. https://doi.org/10.1016/j.cell.2016.05.046.
Bliss SA, Sinha G, Sandiford OA, Williams LM, Engelberth DJ, Guiro K, et al. Mesenchymal stem cell-derived exosomes stimulate cycling quiescence and early breast cancer dormancy in bone marrow. Can Res. 2016;76(19):5832–44. https://doi.org/10.1158/0008-5472.can-16-1092.
Huang MB, Gonzalez RR, Lillard J, Bond VC. Secretion modification region-derived peptide blocks exosome release and mediates cell cycle arrest in breast cancer cells. Oncotarget. 2017;8(7):11302–15. https://doi.org/10.18632/oncotarget.14513.
Lowry MC, Gallagher WM, O’Driscoll L. The role of exosomes in breast cancer. Clin Chem. 2015;61(12):1457–65. https://doi.org/10.1373/clinchem.2015.240028.
Liberati AAD, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–34. https://doi.org/10.1016/j.jclinepi.2009.06.006.
Fang S, Tian H, Li X, Jin D, Li X, Kong J, et al. Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification. PLoS ONE. 2017;12(4):e0175050. https://doi.org/10.1371/journal.pone.0175050.
Domenyuk V, Zhong Z, Stark A, Xiao N, O’Neill HA, Wei X, et al. Plasma exosome profiling of cancer patients by a next generation systems biology approach. Sci Rep. 2017;7:42741. https://doi.org/10.1038/srep42741.
Lee SJ, Lee J, Jung JH, Park HY, Lee C-H, Moon P-G, et al. Exosomal Del-1 as a potent diagnostic marker for breast cancer: a prospective cohort study. J Clin Oncol. 2017;35(15_suppl):11548. https://doi.org/10.1200/JCO.2017.35.15_suppl.11548.
Kibria G, Ramos EK, Lee KE, Bedoyan S, Huang S, Samaeekia R, et al. A rapid, automated surface protein profiling of single circulating exosomes in human blood. Sci Rep. 2016;6:36502. https://doi.org/10.1038/srep36502.
Yang SJ, Wang DD, Li J, Xu HZ, Shen HY, Chen X et al. Predictive role of GSTP1-containing exosomes in chemotherapy-resistant breast cancer. Gene. 2017. https://doi.org/10.1016/j.gene.2017.04.031.
Wang T, Ning K, Lu TX, Sun X, Jin L, Qi X, et al. Increasing circulating exosomes-carrying TRPC5 predicts chemoresistance in metastatic breast cancer patients. Cancer Sci. 2017;108(3):448–54. https://doi.org/10.1111/cas.13150.
Ning K, Wang T, Sun X, Zhang P, Chen Y, Jin J et al. UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer. J Surg Oncol. 2017. https://doi.org/10.1002/jso.24614.
Sueta A, Yamamoto Y, Tomiguchi M, Takeshita T, Ibusuki M, Iwase H. Differential expression of exosomal miRNAs between breast cancer patients with recurrence and no-recurrence. Cancer Res. 2017;77:4. https://doi.org/10.1158/1538-7445.SABCS16-P1-02-13.
Gerratana L, Toffoletto B, Bulfoni M, Cesselli D, Beltrami AP, Di Loreto C, et al. Metastatic breast cancer and circulating exosomes. Hints from an exploratory analysis. Ann Oncol. 2015;26:23–5. https://doi.org/10.1093/annonc/mdv336.37.
Rodriguez M, Silva J, Herrera A, Herrera M, Pena C, Martin P, et al. Exosomes enriched in stemness/metastatic-related mRNAS promote oncogenic potential in breast cancer. Oncotarget. 2015;6(38):40575–87. https://doi.org/10.18632/oncotarget.5818.
Kanbayashi C, Iwata H. Current approach and future perspective for ductal carcinoma in situ of the breast. Jpn J Clin Oncol. 2017. https://doi.org/10.1093/jjco/hyx059.
Kazarian A, Blyuss O, Metodieva G, Gentry-Maharaj A, Ryan A, Kiseleva EM, et al. Testing breast cancer serum biomarkers for early detection and prognosis in pre-diagnosis samples. Br J Cancer. 2017;116(4):501–8. https://doi.org/10.1038/bjc.2016.433.
Orlando L, Viale G, Bria E, Lutrino ES, Sperduti I, Carbognin L, et al. Discordance in pathology report after central pathology review: implications for breast cancer adjuvant treatment. Breast. 2016;30:151–5. https://doi.org/10.1016/j.breast.2016.09.015.
Navani N, Nankivell M, Woolhouse I, Harrison RN, Munavvar M, Oltmanns U, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of intrathoracic lymphadenopathy in patients with extrathoracic malignancy: a multicenter study. J Thorac Oncol. 2011;6(9):1505–9. https://doi.org/10.1097/JTO.0b013e318223c3fe.
Martin M, Ito H. Incidentally discovered intraperitoneal masses. JAMA Surg. 2015;150(7):677–8. https://doi.org/10.1001/jamasurg.2015.0260.
Tang S, Wei L, Sun Y, Zhou F, Zhu S, Yang R, et al. CA153 in breast secretions as a potential molecular marker for diagnosing breast cancer: a meta analysis. PLoS ONE. 2016;11(9):e0163030. https://doi.org/10.1371/journal.pone.0163030.
Fang C, Cao Y, Liu X, Zeng XT, Li Y. Serum CA125 is a predictive marker for breast cancer outcomes and correlates with molecular subtypes. Oncotarget. 2017. https://doi.org/10.18632/oncotarget.19246.
Zhang L, Pan L, Xiang B, Zhu H, Wu Y, Chen M, et al. Potential role of exosome-associated microRNA panels and in vivo environment to predict drug resistance for patients with multiple myeloma. Oncotarget. 2016;7(21):30876–91. https://doi.org/10.18632/oncotarget.9021.
Wen SW, Sceneay J, Lima LG, Wong CS, Becker M, Krumeich S, et al. The biodistribution and immune suppressive effects of breast cancer-derived exosomes. Can Res. 2016;76(23):6816–27. https://doi.org/10.1158/0008-5472.can-16-0868.
Ohuchi N, Suzuki A, Sobue T, Kawai M, Yamamoto S, Zheng YF, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial. Lancet. 2016;387(10016):341–8. https://doi.org/10.1016/s0140-6736(15)00774-6.
Aktas B, Kasimir-Bauer S, Muller V, Janni W, Fehm T, Wallwiener D, et al. Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients. BMC Cancer. 2016;16:522. https://doi.org/10.1186/s12885-016-2587-4.
Madic J, Kiialainen A, Bidard FC, Birzele F, Ramey G, Leroy Q, et al. Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients. Int J Cancer. 2015;136(9):2158–65. https://doi.org/10.1002/ijc.29265.
Chollet-Hinton L, Anders CK, Tse CK, Bell MB, Yang YC, Carey LA, et al. Breast cancer biologic and etiologic heterogeneity by young age and menopausal status in the Carolina Breast Cancer Study: a case–control study. Breast Cancer Res. 2016;18(1):79. https://doi.org/10.1186/s13058-016-0736-y.
Natrajan R, Sailem H, Mardakheh FK, Arias Garcia M, Tape CJ, Dowsett M, et al. Microenvironmental heterogeneity parallels breast cancer progression: a histology-genomic integration analysis. PLoS Med. 2016;13(2):e1001961. https://doi.org/10.1371/journal.pmed.1001961.
Meng F, Liu B, Xie G, Song Y, Zheng X, Qian X et al. Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast. Breast Cancer Res Treat. 2017. https://doi.org/10.1007/s10549-017-4407-1.
Lee MV, Katabathina VS, Bowerson ML, Mityul MI, Shetty AS, Elsayes KM, et al. BRCA-associated cancers: role of imaging in screening, diagnosis, and management. Radiographics. 2017;37(4):1005–23. https://doi.org/10.1148/rg.2017160144.
Reyes ME, Fujii T, Branstetter D, Krishnamurthy S, Masuda H, Wang X, et al. Poor prognosis of patients with triple-negative breast cancer can be stratified by RANK and RANKL dual expression. Breast Cancer Res Treat. 2017;164(1):57–67. https://doi.org/10.1007/s10549-017-4233-5.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants performed by any of the authors.
Rights and permissions
About this article
Cite this article
Wang, M., Ji, S., Shao, G. et al. Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients. Clin Transl Oncol 20, 906–911 (2018). https://doi.org/10.1007/s12094-017-1805-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-017-1805-0