title: Analysis of exosome release and its prognostic value in human colorectal cancer.
abstract: A significant proportion of extracellular nucleic acids in plasma circulate highly protected in tumor-specific exosomes, but it is unclear how the release of exosomes is modulated in carcinogenesis. We quantified by cytometry exosomes in plasma of 91 colorectal cancer patients to evaluate their potential as a tumor indicator and their repercussions on diagnosis and prognosis. We examined the involvement of TSAP6, a TP53-regulated gene involved in the regulation of vesicular secretion, in levels of circulating exosomes in plasma of colorectal patients and in HCT116 TP53-(wild-type and null) human colorectal cancer cell lines. The fraction of exosomes in cancer patients was statistically higher than in healthy controls (mean rank ¼ 53.93 vs. 24.35). High levels of exosomes in plasma of patients correlated with high levels of carcino-embryonic antigen (P ¼ 0.029) and with poorly differentiated tumors (P ¼ 0.039) and tended to have shorter overall survival than patients with low levels (P ¼ 0.056). Release of exosomes did not correlate with TSAP6 expression; and regulation of TSAP6 by TP53 was not shown either in tumor samples or in HCT116 cell lines. Although it was not suggested that the TP53/TSAP6 pathway regulates the release of exosomes into the plasma of colorectal cancer patients, the level of circulating exosomes may be used as a tumor indicator, because it correlates with poor prognosis parameters and shorter survival.
authors.affiliation: Departmentof MedicalOncology, University Hospital Puerta de Hierro, Majadahonda, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Silva
authors.forename: V
authors.initials: V
authors.lastname: Garcia
authors.forename: M
authors.initials: M
authors.lastname: Rodriguez
authors.forename: M
authors.initials: M
authors.lastname: Compte
authors.forename: E
authors.initials: E
authors.lastname: Cisneros
authors.forename: P
authors.initials: P
authors.lastname: Veguillas
authors.forename: J M
authors.initials: JM
authors.lastname: Garcia
authors.forename: G
authors.initials: G
authors.lastname: Dominguez
authors.forename: Y
authors.initials: Y
authors.lastname: Campos-Martin
authors.forename: J
authors.initials: J
authors.lastname: Cuevas
authors.forename: C
authors.initials: C
authors.lastname: Peña
authors.forename: M
authors.initials: M
authors.lastname: Herrera
authors.forename: R
authors.initials: R
authors.lastname: Diaz
authors.forename: N
authors.initials: N
authors.lastname: Mohammed
authors.forename: F
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000097:blood; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000401:mortality; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016158:Genes, p53; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D022142:Secretory Vesicles / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D018797:Cell Cycle Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D010088:Oxidoreductases; C486677:STEAP3 protein, human