CEACAM6 Serves As a Biomarker for Leptomeningeal Metastasis in Lung Adenocarcinoma

Overview

Journal Cancer Med

Specialty Oncology

Date 2022 Sep 9

PMID 36082960

Authors

Xueying Wang

Xuemei Tang

Jiahui Gu

Ziwei Sun

Shengrui Yang

Yuan Mu

Ming Guan

Kun Chen

Wei Liu

Haoyu Ruan

Jian Xu

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Diagnosis of leptomeningeal metastasis (LM) is challenging. In our previous study, CEACAM6 mRNA was found to be highly expressed in the circulating tumor cells of cerebrospinal fluid (CSF) from patients with lung adenocarcinoma with LM (LUAD-LM). The aim of this study was to identify whether CEACAM6 could be used as a biomarker for LUAD-LM.

Materials And Methods: The level of CEACAM6 was determined by enzyme-linked immunosorbent assay (ELISA) in CSF from 40 LUAD-LM and 44 normal controls, and additional serum samples from 138 LUAD patients, including 12 LUAD-LM patients, and 30 healthy controls. Carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and neuron-specific enolase (NSE) levels in the CSF and sera were detected by chemiluminescent immunoassay. Receiver operating characteristic curve was plotted to evaluate the diagnostic performance for LUAD-LM.

Results: CSF CEACAM6 level was higher in LUAD-LM than that in normal controls. In serum, LUAD patients had a higher level of CAECAM6 than healthy controls, and LM patients had the highest level among them. Serum CEACAM6 had a higher AUC than CEA in differentiating LM from non-LM in LUAD patients (0.95 vs. 0.64, p < 0.001).

Conclusion: CEACAM6 may serve as a potential biomarker in diagnosing LUAD-LM.

Citing Articles

Case report: A case report and literature review on the efficacy of high-dose aumolertinib combined intrathecal pemetrexed by Ommaya reservoir for EGFR-mutated NSCLC with leptomeningeal metastasis as the initial symptoms.

Zhong M, Zhou L, Guo J, Chen C, Wang W, Huang X Front Oncol. 2025; 15:1502934.

PMID: 39949743 PMC: 11821504. DOI: 10.3389/fonc.2025.1502934.

CEACAM6 expression and function in tumor biology: a comprehensive review.

Zhao D, Cai F, Liu X, Li T, Zhao E, Wang X Discov Oncol. 2024; 15(1):186.

PMID: 38796667 PMC: 11127906. DOI: 10.1007/s12672-024-01053-6.

Diagnostic value of cerebrospinal fluid human epididymis protein 4 for leptomeningeal metastasis in lung adenocarcinoma.

Li X, Chen K, Li J, Tang X, Ruan H, Guan M Front Immunol. 2024; 15:1339914.

PMID: 38304432 PMC: 10830695. DOI: 10.3389/fimmu.2024.1339914.

FABP6 serves as a new therapeutic target in esophageal tumor.

Zhang D, Zhao F, Liu H, Guo P, Li Z, Li S Aging (Albany NY). 2024; 16(2):1640-1662.

PMID: 38277205 PMC: 10866426. DOI: 10.18632/aging.205448.

The emerging roles of CEACAM6 in human cancer (Review).

Wu G, Wang D, Xiong F, Wang Q, Liu W, Chen J Int J Oncol. 2024; 64(3).

PMID: 38240103 PMC: 10836497. DOI: 10.3892/ijo.2024.5615.

References

Grunnet M, Sorensen J . Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer. 2011; 76(2):138-43. DOI: 10.1016/j.lungcan.2011.11.012. View

Wang X, Tang X, Gu J, Sun Z, Yang S, Mu Y . CEACAM6 serves as a biomarker for leptomeningeal metastasis in lung adenocarcinoma. Cancer Med. 2022; 12(4):4521-4529. PMC: 9972070. DOI: 10.1002/cam4.5221. View

Hamidi H, Ivaska J . Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer. 2018; 18(9):533-548. PMC: 6629548. DOI: 10.1038/s41568-018-0038-z. View

Hyun J, Jeong I, Joung A, Cho H, Kim S, Kim H . Leptomeningeal metastasis: Clinical experience of 519 cases. Eur J Cancer. 2016; 56:107-114. DOI: 10.1016/j.ejca.2015.12.021. View

Hong K, Shin M, Yoon S, Ji G, Moon Y, Lee O . 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. View

Johnson B, Mahadevan D . Emerging Role and Targeting of Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) in Human Malignancies. Clin Cancer Drugs. 2016; 2(2):100-111. PMC: 4997943. DOI: 10.2174/2212697X02666150602215823. View

Ordonez C, Zhai A, Camacho-Leal P, DeMarte L, Fan M, Stanners C . GPI-anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin alpha5beta1-fibronectin interaction. J Cell Physiol. 2006; 210(3):757-65. DOI: 10.1002/jcp.20887. View

Singer B, Scheffrahn I, Kammerer R, Suttorp N, Ergun S, Slevogt H . Deregulation of the CEACAM expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells. PLoS One. 2010; 5(1):e8747. PMC: 2807459. DOI: 10.1371/journal.pone.0008747. View

Kim E, Cha Y, Jeong S, Chang Y . Overexpression of CEACAM6 activates Src-FAK signaling and inhibits anoikis, through homophilic interactions in lung adenocarcinomas. Transl Oncol. 2022; 20:101402. PMC: 8968058. DOI: 10.1016/j.tranon.2022.101402. View

10.

Walbert T, Groves M . Known and emerging biomarkers of leptomeningeal metastasis and its response to treatment. Future Oncol. 2010; 6(2):287-97. DOI: 10.2217/fon.09.167. View

11.

Codreanu S, Hoeksema M, Slebos R, Zimmerman L, Rahman S, Li M . Identification of Proteomic Features To Distinguish Benign Pulmonary Nodules from Lung Adenocarcinoma. J Proteome Res. 2017; 16(9):3266-3276. PMC: 6339813. DOI: 10.1021/acs.jproteome.7b00245. View

12.

Remon J, Le Rhun E, Besse B . Leptomeningeal carcinomatosis in non-small cell lung cancer patients: A continuing challenge in the personalized treatment era. Cancer Treat Rev. 2017; 53:128-137. DOI: 10.1016/j.ctrv.2016.12.006. View

13.

Duxbury M, Ito H, Ashley S, Whang E . c-Src-dependent cross-talk between CEACAM6 and alphavbeta3 integrin enhances pancreatic adenocarcinoma cell adhesion to extracellular matrix components. Biochem Biophys Res Commun. 2004; 317(1):133-41. DOI: 10.1016/j.bbrc.2004.03.018. View

14.

Ruan H, Zhou Y, Shen J, Zhai Y, Xu Y, Pi L . Circulating tumor cell characterization of lung cancer brain metastases in the cerebrospinal fluid through single-cell transcriptome analysis. Clin Transl Med. 2020; 10(8):e246. PMC: 7737787. DOI: 10.1002/ctm2.246. View

15.

Wu S, Arundhathi A, Wang H, Chen C, Cheng T, Yuan S . Migration and invasion of NSCLC suppressed by the downregulation of Src/focal adhesion kinase using single, double and tetra domain anti- CEACAM6 antibodies. Transl Oncol. 2021; 14(7):101057. PMC: 8105299. DOI: 10.1016/j.tranon.2021.101057. View

16.

Son S, Yun J, Lee S, Han H, Lim Y, Woo C . Therapeutic Effect of pHLIP-mediated CEACAM6 Gene Silencing in Lung Adenocarcinoma. Sci Rep. 2019; 9(1):11607. PMC: 6717735. DOI: 10.1038/s41598-019-48104-5. View

17.

Wang Y, Luo N, Gao Y, Wu Y, Qin X, Qi Y . The joint detection of CEA and ctDNA in cerebrospinal fluid: an auxiliary tool for the diagnosis of leptomeningeal metastases in cancer. J Cancer Res Clin Oncol. 2022; 149(5):1679-1690. DOI: 10.1007/s00432-022-04053-7. View

18.

Sasaki S, Yoshioka Y, Ko R, Katsura Y, Namba Y, Shukuya T . Diagnostic significance of cerebrospinal fluid EGFR mutation analysis for leptomeningeal metastasis in non-small-cell lung cancer patients harboring an active EGFR mutation following gefitinib therapy failure. Respir Investig. 2016; 54(1):14-9. DOI: 10.1016/j.resinv.2015.07.001. View

19.

Beauchemin N, Arabzadeh A . Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013; 32(3-4):643-71. DOI: 10.1007/s10555-013-9444-6. View

20.

Li Y, Jiang B, Yang J, Tu H, Zhou Q, Guo W . Leptomeningeal Metastases in Patients with NSCLC with EGFR Mutations. J Thorac Oncol. 2016; 11(11):1962-1969. DOI: 10.1016/j.jtho.2016.06.029. View