Levels of CEACAM6 in Peripheral Blood Are Elevated in Patients with Plasma Cell Disorders: A Potential New Diagnostic Marker and a New Therapeutic Target?
Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
30809317
PubMed Central
PMC6369456
DOI
10.1155/2019/1806034
Knihovny.cz E-zdroje
- MeSH
- CD antigeny krev metabolismus MeSH
- GPI-vázané proteiny krev metabolismus MeSH
- kostní dřeň metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom krev MeSH
- molekuly buněčné adheze krev metabolismus MeSH
- nádorové biomarkery krev metabolismus MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- CD antigeny MeSH
- CEACAM6 protein, human MeSH Prohlížeč
- GPI-vázané proteiny MeSH
- molekuly buněčné adheze MeSH
- nádorové biomarkery MeSH
INTRODUCTION: The prognosis of multiple myeloma is still unfavorable due to inherent characteristics of the disease and the often-delayed diagnosis due to widespread and unspecific symptoms such as back pain and fatigue. Therefore, a simple diagnostic blood test would be helpful to speed up the diagnostic procedure in such patients (pts.). Here, we evaluated the diagnostic value of plasma levels of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in the peripheral blood and bone marrow of pts. with plasma cell disorders and in healthy controls. MATERIALS AND METHODS: Immunoreactive CEACAM6 was determined in the peripheral blood and bone marrow (n = 95/100) of pts. with monoclonal gammopathy of unknown significance (MGUS: 28/37), newly diagnosed multiple myeloma (NDMM: 42/40), and relapsed/refractory multiple myeloma (RRMM: 25/23) by sandwich ELISA. RESULTS: Median CEACAM6 levels in the peripheral blood of pts. with plasma cell disorders were significantly higher than those of healthy controls (healthy controls: 15.2 pg/ml (12.1-17.1); MGUS: 19.0 pg/ml (16.4-22.5); NDMM: 18.0 pg/ml (13.4-21.2); and RRMM: 18.9 pg/ml (15.2-21.5); p < 0.001). Plasma levels of CEACAM6 discriminated healthy subjects from MGUS/NDMM pts. (AUC = 0.71, 95% CI: 0.6-0.8); i.e., a CEACAM6 level > 17.3 pg/ml has an 82% (95% CI: 70-90) predictive probability for the identification of MGUS or NDMM. Moreover, CEACAM6 levels in the bone marrow were significantly higher in RRMM pts. than in NDMM pts. (p = 0.04), suggesting a role of this molecule in disease progression. CONCLUSION: CEACAM6 plasma levels can noninvasively identify pts. with a plasma cell disorder and should be evaluated prospectively as a potential diagnostic marker. Moreover, due to high CEACAM6 levels in the bone marrow in RRMM pts., this adhesion molecule might be a therapeutic target in multiple myeloma pts.
Department of Clinical Hematology University Hospital Brno Brno Czech Republic
Department of Hematooncology University Hospital Ostrava Ostrava Czech Republic
Department of Internal Medicine 5 Medical University of Innsbruck Innsbruck Austria
Faculty of Medicine University of Ostrava Ostrava Czech Republic
Zobrazit více v PubMed
Jantscheff P., Terracciano L., Lowy A., et al. Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance. Journal of Clinical Oncology. 2003;21(19):3638–3646. doi: 10.1200/JCO.2003.55.135. PubMed DOI
Zhao Z. S., Li L., Wang H. J., Wang Y. Y. Expression and prognostic significance of CEACAM6, ITGB1, and CYR61 in peripheral blood of patients with gastric cancer. Journal of Surgical Oncology. 2011;104(5):525–529. doi: 10.1002/jso.21984. PubMed DOI
Blumenthal R. D., Leon E., Hansen H. J., Goldenberg D. M. Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers. BMC Cancer. 2007;7(1):p. 2. doi: 10.1186/1471-2407-7-2. PubMed DOI PMC
Zang M., Zhang Y., Zhang B., et al. CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2015;1852(5):1020–1028. doi: 10.1016/j.bbadis.2015.02.005. PubMed DOI
Ru G. Q., Han Y., Wang W., et al. CEACAM6 is a prognostic biomarker and potential therapeutic target for gastric carcinoma. Oncotarget. 2017;8(48):83673–83683. doi: 10.18632/oncotarget.19415. PubMed DOI PMC
Duxbury M. S., Matros E., Clancy T., et al. CEACAM6 is a novel biomarker in pancreatic adenocarcinoma and PanIN lesions. Annals of Surgery. 2005;241(3):491–496. doi: 10.1097/01.sla.0000154455.86404.e9. PubMed DOI PMC
Gebauer F., Wicklein D., Horst J., et al. Carcinoembryonic antigen-related cell adhesion molecules (CEACAM) 1, 5 and 6 as biomarkers in pancreatic cancer. PLoS One. 2014;9(11, article e113023) doi: 10.1371/journal.pone.0113023. PubMed DOI PMC
Cheng T. M., Murad Y. M., Chang C. C., et al. Single domain antibody against carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) inhibits proliferation, migration, invasion and angiogenesis of pancreatic cancer cells. European Journal of Cancer. 2014;50(4):713–721. doi: 10.1016/j.ejca.2012.07.019. PubMed DOI
Rodia M. T., Ugolini G., Mattei G., et al. Systematic large-scale meta-analysis identifies a panel of two mRNAs as blood biomarkers for colorectal cancer detection. Oncotarget. 2016;7(21):30295–30306. doi: 10.18632/oncotarget.8108. PubMed DOI PMC
Hong K. P., Shin M. H., Yoon S., et al. Therapeutic effect of anti CEACAM6 monoclonal antibody against lung adenocarcinoma by enhancing anoikis sensitivity. Biomaterials. 2015;67:32–41. doi: 10.1016/j.biomaterials.2015.07.012. PubMed DOI
Niu G., Murad Y. M., Gao H., et al. Molecular targeting of CEACAM6 using antibody probes of different sizes. Journal of Controlled Release. 2012;161(1):18–24. doi: 10.1016/j.jconrel.2012.04.043. PubMed DOI PMC
Witzens-Harig M., Hose D., Junger S., et al. Tumor cells in multiple myeloma patients inhibit myeloma-reactive T cells through carcinoembryonic antigen-related cell adhesion molecule-6. Blood. 2013;121(22):4493–4503. doi: 10.1182/blood-2012-05-429415. PubMed DOI
The International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. British Journal of Haematology. 2003;121(5):749–757. doi: 10.1046/j.1365-2141.2003.04355.x. PubMed DOI
Steiner N., Hajek R., Sevcikova S., et al. High levels of FLT3-ligand in bone marrow and peripheral blood of patients with advanced multiple myeloma. PLoS One. 2017;12(7, article e0181487) doi: 10.1371/journal.pone.0181487. PubMed DOI PMC
Kariyawasan C. C., Hughes D. A., Jayatillake M. M., Mehta A. B. Multiple myeloma: causes and consequences of delay in diagnosis. QJM: An International Journal of Medicine. 2007;100(10):635–640. doi: 10.1093/qjmed/hcm077. PubMed DOI
Graziani G., Herget G. W., Ihorst G., et al. Time from first symptom onset to the final diagnosis of multiple myeloma — possible risks and future solutions: large retrospective and confirmatory prospective ‘Deutsche Studiengruppe Multiples Myelom’ (DSMM) analysis. Blood. 2017;130, article 4710 PubMed
Blumenthal R. D., Hansen H. J., Goldenberg D. M. Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (carcinoembryonic antigen) Cancer Research. 2005;65(19):8809–8817. doi: 10.1158/0008-5472.CAN-05-0420. PubMed DOI
Zang M., Hu L., Cao S., et al. Dual role of carcinoembryonic antigen-related cell adhesion molecule 6 expression in predicting the overall survival of gastric cancer patients. Scientific Reports. 2017;7(1, article 10773) doi: 10.1038/s41598-017-11482-9. PubMed DOI PMC
Johnson B., Mahadevan D. Emerging role and targeting of carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) in human malignancies. Clinical Cancer Drugs. 2015;2(2):100–111. doi: 10.2174/2212697X02666150602215823. PubMed DOI PMC
Imakiire T., Kuroki M., Shibaguchi H., et al. Generation, immunologic characterization and antitumor effects of human monoclonal antibodies for carcinoembryonic antigen. International Journal of Cancer. 2004;108(4):564–570. doi: 10.1002/ijc.11608. PubMed DOI