Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Clinical and experimental studies regarding the expression and diagnostic value of carcinoembryonic antigen-related cell adhesion molecule 1 in non-small-cell lung cancer

Authors: Mu-qing Zhou, Yan Du, Yi-wen Liu, Ying-zhi Wang, Yi-qing He, Cui-xia Yang, Wen-juan Wang, Feng Gao

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in non-small-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC.

Methods

The expression of the serum CEACAM1 was determined by enzyme-linked immunosorbent assay. The protein expression and the location of CEACAM1 in tumours were observed by immunohistochemical staining. The CEACAM1 mRNA levels in tumour and normal adjacent tissues were measured using quantitative real-time PCR, and the expression patterns and the rate of CEACAM1-S and CEACAM1-L were analysed by reverse transcription-PCR.

Results

Serum CEACAM1 levels were significantly higher in NSCLC patients compared with that from normal healthy controls (P <0.0001). 17 patients (81%) among 21 showed high expression of CEACAM1 by immunohistochemical staining. Although no significant differences were found between tumour and normal tissues on mRNA expression levels of CEACAM1 (P >0.05), the CEACAM1-S and the CEACAM1-S/L (S: L) ratios were significantly higher in tumour than normal tissues (P <0.05).

Conclusions

Our data indicated that the serum levels of CEACAM1 could discriminate lung cancer patients from health donors and that CEACAM1 might be a useful marker in early diagnosis of NSCLC. Moreover, our results showed that the expression patterns of CEACAM1 isoforms could be changed during oncogenesis, even when total CEACAM1 in tumour tissues did not show significant changes. Our study suggested that the expression ratios of CEACAM1-S/CEACAM1-L might be a better diagnostic indicator in NSCLC than the quantitative changes of CEACAM1.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Canc J Clin. 2011, 61: 69-90. 10.3322/caac.20107.CrossRef
2.
Gray-Owen SD, Blumberg RS: CEACAM1: contact-dependent control of immunity. Nat Rev Immunol. 2006, 6: 433-446. 10.1038/nri1864.CrossRefPubMed
3.
Yokoyama S, Chen CJ, Nguyen T, Shively JE: Role of CEACAM1 isoforms in an in vivo model of mammary morphogenesis: mutational analysis of the cytoplasmic domain of CEACAM1-4S reveals key residues involved in lumen formation. Oncogene. 2007, 26: 7637-7646. 10.1038/sj.onc.1210577.CrossRefPubMed
4.
Gu A, Tsark W, Holmes KV, Shively JE: Role of Ceacam1 in VEGF induced vasculogenesis of murine embryonic stem cell-derived embryoid bodies in 3D culture. Exp Cell Res. 2009, 315: 1668-1682. 10.1016/j.yexcr.2009.02.026.CrossRefPubMedPubMedCentral
5.
Klaile E, Müller MM, Kannicht C, Singer BB, Lucka L: CEACAM1 functionally interacts with filamin A and exerts a dual role in the regulation of cell migration. J Cell Sci. 2005, 118: 5513-5524. 10.1242/jcs.02660.CrossRefPubMed
6.
Abou-Rjaily GA, Lee SJ, May D, Al-Share QY, DeAngelis AM, Ruch RJ, Neumaier M, Kalthoff H, Lin S-H, Najjar SM: CEACAM1 modulates epidermal growth factor receptor–mediated cell proliferation. J Clin Invest. 2004, 114: 944-952.CrossRefPubMedPubMedCentral
7.
Scheffrahn I, Singer BB, Sigmundsson K, Lucka L, Obrink B: Control of density-dependent, cell state-specific signal transduction by the cell adhesion molecule CEACAM1, and its influence on cell cycle regulation. Exp Cell Res. 2005, 307: 427-435. 10.1016/j.yexcr.2005.03.030.CrossRefPubMed
8.
Müller MM, Singer BB, Klaile E, Öbrink B, Lucka L: Transmembrane CEACAM1 affects integrin-dependent signaling and regulates extracellular matrix protein–specific morphology and migration of endothelial cells. Blood. 2005, 105: 3925-3934. 10.1182/blood-2004-09-3618.CrossRefPubMed
9.
Muller MM, Klaile E, Vorontsova O, Singer BB, Obrink B: Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and recruitment of SHP-2 and c-Src. J Cell Biol. 2009, 187: 569-581. 10.1083/jcb.200904150.CrossRefPubMedPubMedCentral
10.
Busch C, Hanssen TA, Wagener C, OB B: Down-regulation of CEACAM1 in human prostate cancer: correlation with loss of cell polarity, increased proliferation rate, and Gleason grade 3 to 4 transition. Hum Pathol. 2002, 33: 290-298. 10.1053/hupa.2002.32218.CrossRefPubMed
11.
Sundberg U, Beauchemin N, Öbrink B: The cytoplasmic domain of CEACAM1-L controls its lateral localization and the organization of desmosomes in polarized epithelial cells. J Cell Sci. 2004, 117: 1091-1104. 10.1242/jcs.00944.CrossRefPubMed
12.
Watt SM, Teixeira AM, Zhou GQ, Doyonnas R, Zhang Y, Grunert F, Blumberg RS, Kuroki M, Skubitz KM, Bates PA: Homophilic adhesion of human CEACAM1 involves N-terminal domain interactions: structural analysis of the binding site. Blood. 2001, 98: 1469-1479. 10.1182/blood.V98.5.1469.CrossRefPubMed
13.
Song J, Cao Z, Yoon J, Nam S, Kim S, Lee J, Park W: Genetic alterations and expression pattern of CEACAM1 in colorectal adenomas and cancers. Pathol Oncol Res. 2010, 17: 67-74.CrossRefPubMed
14.
Tanaka K, Hinoda Y, Takahashi H, Sakamoto H, Nakajima Y, Imai K: Decreased expression of biliary glycoprotein in hepatocellular carcinomas. Int J Canc. 1997, 74: 15-19. 10.1002/(SICI)1097-0215(19970220)74:1<15::AID-IJC3>3.0.CO;2-3.CrossRef
15.
Bamberger AM, Kappes H, Methner C, Rieck G, Brümmer J, Wagener C, Löning T, Milde-Langosch K: Expression of the adhesion molecule CEACAM1 (CD66a, BGP, C-CAM) in breast cancer is associated with the expression of the tumor-suppressor genes Rb, Rb2, and p27. Virchows Arch. 2002, 440: 139-144. 10.1007/s00428-001-0554-0.CrossRefPubMed
16.
Kammerer R, Riesenberg R, Weiler C, Lohrmann J, Schleypen J, Zimmermann W: The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma. J Pathol. 2004, 204: 258-267. 10.1002/path.1657.CrossRefPubMed
17.
Tilki D, Irmak S, Oliveira-Ferrer L, Hauschild J, Miethe K, Atakaya H, Hammerer P, Friedrich MG, Schuch G, Galalae R, et al: CEA-related cell adhesion molecule-1 is involved in angiogenic switch in prostate cancer. Oncogene. 2006, 25: 4965-4974. 10.1038/sj.onc.1209514.CrossRefPubMed
18.
Hsieh J, Luo W, Song W, Wang Y, Kleinerman D, Van N, Lin S: Tumor suppressive role of an androgen-regulated epithelial cell adhesion molecule (C-CAM) in prostate carcinoma cell revealed by sense and antisense approaches. Canc Res. 1995, 55: 190-197.
19.
Markel G, Ortenberg R, Seidman R, Sapoznik S, Koren-Morag N, Besser MJ, Bar J, Shapira R, Kubi A, Nardini G, et al: Systemic dysregulation of CEACAM1 in melanoma patients. Canc Immunol Immunother. 2010, 59: 365-374.CrossRef
20.
Liu W, Wei W, Winer D, Bamberger AM, Bamberger C, Wagener C, Ezzat S, Asa SL: CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases. Oncogene. 2006, 26: 2747-2758.CrossRefPubMed
21.
Simeone DM, Ji B, Banerjee M, Arumugam T, Li D, Anderson MA, Bamberger AM, Greenson J, Brand RE, Ramachandran V, Logsdon CD: CEACAM1, a novel serum biomarker for pancreatic cancer. Pancreas. 2007, 34: 436-443. 10.1097/MPA.0b013e3180333ae3.CrossRefPubMed
22.
Sivan S, Suzan F, Rona O, Tamar H, Vivian B, Tamar P, Jacob S, Gal M, Michal L: Serum CEACAM1 correlates with disease progression and survival in malignant melanoma patients. Clin Dev Immunol. 2010, 59: 215-230.
23.
Laack E, Nikbakht H, Peters A, Kugler C, Jasiewicz Y, Edler L, Brümmer J, Schumacher U, Hossfeld D: Expression of CEACAM1 in adenocarcinoma of the lung: a factor of independent prognostic significance. J Clin Oncol. 2002, 20: 4279-4284. 10.1200/JCO.2002.08.067.CrossRefPubMed
24.
Dango S, Sienel W, Schreiber M, Stremmel C, Kirschbaum A, Pantel K, Passlick B: Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) is associated with increased angiogenic potential in non-small-cell lung cancer. Lung Canc. 2008, 60: 426-433. 10.1016/j.lungcan.2007.11.015.CrossRef
25.
Lee MK, Kim JH, Lee CH, Kim JM, Kang CD, Kim YD, Choi KU, Kim HW, Kim JY, Park do Y, Sol MY: Clinicopathological significance of BGP expression in non-small-cell lung carcinoma: relationship with histological type, microvessel density and patients' survival. Pathology. 2006, 38: 555-560. 10.1080/00313020601024029.CrossRefPubMed
26.
Th MI, Schult-Kronefeld O, Burkholder I, Schuch G, Andritzky B, Kastendieck H, Edler L, Wagener C, Bokemeyer C, Schumacher U: Expression of CEACAM-1 in pulmonary adenocarcinomas and their metastases. Anticancer Res. 2009, 29: 249-254.
27.
Zhou XH: Statistical methods in diagnestie medicine. Edited by: MCCLISH DK. 2002, New York: Wiley & Sons InterscienceCrossRef
28.
Obuchowski NA, Lieber ML, Wians FH: ROC curves in clinical chemistry: Uses, misuses, and possible solutions. Clin Chem. 2004, 50: 1118-1125. 10.1373/clinchem.2004.031823.CrossRefPubMed
29.
Zhou C-J, Liu B, Zhu K-X, Zhang Q-H, Zhang T-G, Xu W-H, Wang H-B, Yu W-H, Qu Y-D, Wang H-J, et al: The different expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and possible roles in gastric carcinomas. Pathol Res Pract. 2009, 205: 483-489. 10.1016/j.prp.2009.01.006.CrossRefPubMed
30.
Sienel W, Dango S, Woelfle U, Morresi-Hauf A, Wagener C, Brümmer J, Mutschler W, Passlick B, Pantel K: Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 promotes progression of non-small cell lung cancer. Clin Canc Res. 2003, 9: 2260-2266.
31.
Wang L, Lin SH, Wu WG, Kemp BL, Walsh GL, Hong WK, Mao L: C-CAM1, a candidate tumor suppressor gene, is abnormally expressed in primary lung cancers. Clin Canc Res. 2000, 6: 2988-
32.
Gaur S, Shively JE, Yen Y, Gaur RK: Altered splicing of CEACAM1 in breast cancer: Identification of regulatory sequences that control splicing of CEACAM1 into long or short cytoplasmic domain isoforms. Mol Canc. 2008, 7: 1-12.
33.
Kuespert K, Pils S, Hauck C: CEACAMs: their role in physiology and pathophysiology. Curr Opin Cell Biol. 2006, 18: 565-571. 10.1016/j.ceb.2006.08.008.CrossRefPubMed
34.
Nouvion A-L, Oubaha M, LeBlanc S, Davis EC, Jastrow H, Kammerer R, Breton V, Turbide C, Ergun S, Gratton J-P, Beauchemin N: CEACAM1: a key regulator of vascular permeability. J Cell Sci. 2010, 123: 4221-4230. 10.1242/jcs.073635.CrossRefPubMed
35.
Ieda J, Yokoyama S, Tamura K, Takifuji K, Hotta T, Matsuda K, Oku Y, Nasu T, Kiriyama S, Yamamoto N, et al: Re-expression of CEACAM1 long cytoplasmic domain isoform is associated with invasion and migration of colorectal cancer. Int J Canc. 2011, 129: 1351-1361. 10.1002/ijc.26072.CrossRef
36.
Draberova L, Cerna H, Brodska H, Boubelik M, Watt SM, Stanners CP, Draber P: Soluble isoforms of CEACAM1 containing the A2 domain: increased serum levels in patients with obstructive jaundice and differences in 3-fucosyl-N-acetyl-lactosamine moiety. Immunology. 2000, 101: 279-287. 10.1046/j.1365-2567.2000.00113.x.CrossRefPubMedPubMedCentral
37.
Svenberg T, Wahren B, Hammarstrom S: Elevated serum levels of a biliary glycoprotein (BGP I) in patients with liver or biliary tract disease. Clin Exp Immunol. 1979, 36: 317-325.PubMedPubMedCentral
38.
Ergun S, Kilik N, Ziegeler G, Hansen A, Nollau P, Gotze J, Wurmbach JH, Horst A, Weil J, Fernando M, Wagener C: CEA-related cell adhesion molecule 1: a potent angiogenic factor and a major effector of vascular endothelial growth factor. Mol Cell. 2000, 5: 311-320. 10.1016/S1097-2765(00)80426-8.CrossRefPubMed
39.
Nittka S, Bohm C, Zentgraf H, Neumaier M: The CEACAM1-mediated apoptosis pathway is activated by CEA and triggers dual cleavage of CEACAM1. Oncogene. 2008, 27: 3721-3728. 10.1038/sj.onc.1211033.CrossRefPubMed
40.
Tilki D, Singer BB, Shariat SF, Behrend A, Fernando M, Irmak S, Buchner A, Hooper AT, Stief CG, Reich O, Ergün S: CEACAM1: A Novel Urinary Marker for Bladder Cancer Detection. Eur Urol. 2010, 57: 648-654. 10.1016/j.eururo.2009.05.040.CrossRefPubMed
41.
Ohwada A, Takahashi H, Nagaoka I, Kira S: Biliary glycoprotein mRNA expression is increased in primary lung cancer, especially in squamous cell carcinoma. Am J Respir Cell Mol Biol. 1994, 11: 214-220. 10.1165/ajrcmb.11.2.8049082.CrossRefPubMed
42.
Singer BB, Scheffrahn I, Heymann R, Sigmundsson K, Kammerer R, Obrink B: Carcinoembryonic antigen-related cell adhesion molecule 1 expression and signaling in human, mouse, and rat leukocytes: evidence for replacement of the short cytoplasmic domain isoform by glycosylphosphatidylinositol-linked proteins in human leukocytes. J Immunol. 2002, 168: 5139-5146.CrossRefPubMed
43.
Guo J-Q, Yu W-H, Wang H-J, Liu B, Zhu K-X, Zhang Q-H, Zhang T-G, Xu W-H, Wang H-B, Wu H-L, Zhou C-J: Different expression patterns of CEACAM1 and its impacts on Angiogenesis in Gastric Nonneoplastic and Neoplastic Lesions. Ann Surg Oncol. 2012, 19: 365-374.CrossRef
Metadata
Title
Clinical and experimental studies regarding the expression and diagnostic value of carcinoembryonic antigen-related cell adhesion molecule 1 in non-small-cell lung cancer
Authors
Mu-qing Zhou
Yan Du
Yi-wen Liu
Ying-zhi Wang
Yi-qing He
Cui-xia Yang
Wen-juan Wang
Feng Gao
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-359

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue

Research article

Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade

Research article

Long-term prospective longitudinal evaluation of emotional distress and quality of life in cervical cancer patients who remained disease-free 2-years from diagnosis

Case report

Separate episodes of capillary leak syndrome and pulmonary hypertension after adjuvant gemcitabine and three years later after nab-paclitaxel for metastatic disease

Research article

Suppression of thymosin β10 increases cell migration and metastasis of cholangiocarcinoma

Research article

Association between polymorphisms in ERCC2 gene and oral cancer risk: evidence from a meta-analysis

Research article

Negative transcriptional control of ERBB2 gene by MBP-1 and HDAC1: diagnostic implications in breast cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits