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

Abstract

BackgroundCarcinoembryonic 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.MethodsThe 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.ResultsSerum 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).ConclusionsOur 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.

The Roles of Carcinoembryonic Antigen in Liver Metastasis and Therapeutic Approaches

“…Unlike CEA and CEACAM6, CEACAM1 harbors a transmembrane domain and has alternative splicing variants. The expression ratio of the CEACAM1 long (CEACAM1-L) and short (CEACAM1-S) isoform is related with tumorigenesis [39–42]. …”

“…Elevations of serum CEA of 50–60% can occur [50, 51]. CEACAM1, CEACAM6, and NCA-90 are also used prognostically to predict tumor recurrence of breast, lung, and colorectal cancers [42, 52–55]. …”

Urinary Protein Biomarkers in the Early Detection of Lung Cancer

“…A separate study found CEACAM-1 expression in 81.3% of primary tumors from NSCLC patients with preserved expression in lymph node and hematogenous metastases which was negatively correlated with overall and progression-free survival (34). An association between NSCLC and serum CEACAM-1 levels has been reported recently (35). To the best of our knowledge, the current study is the first to report such an association regarding urine CEACAM-1 levels.…”

Roles of CEACAM1 in cell communication and signaling of lung cancer and other diseases

“…CEACAM1-L is the predominant expression form in normal lung tissues [60], while CEACAM1-S is predominantly expressed in most of NSCLC tissues associated with the incidence of NSCLC, especially S-isoform. Ratios of CEACAM1-S and CEACAM1-L were higher in NSCLC [61], indicating that CEACAM1-L and CEACAM1-S may participate in lung tumorigenesis, as explained in Fig. 6.…”

“…Subsequently, SHP-1 is recruited to dephosphorylation of the p85α-binding motif of TLR2, which abrogates formation of the p85α-TLR2 signaling complex. This leads to suppress TLR2-dependent activation of the PI3K-Akt pathway, which reduces NF-кB-dependent antibacterial responses of pulmonary epithelial cells NSCLC [61], as a key factor for the early detection lung cancer and a potential therapeutic target for NSCLC.…”