Levels of CEACAM6 in Peripheral Blood Are Elevated in Patients with Plasma Cell Disorders: A Potential New Diagnostic Marker and a New Therapeutic Target?

Abstract

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.

New CEACAM-targeting 2A3 single-domain antibody-based chimeric antigen receptor T-cells produce anticancer effects in vitro and in vivo

“…Interestingly, in breast cancer, CEACAM6 status has been shown to be 3 higher in both ER-positive tamoxifen-resistant breast cancer and HER-positive trastuzumab-resistant breast cancer than in treatment-responsive disease [21,28], suggesting CEACAM6 as a potential target for the subsequent lines of therapy. Because of its recognized role in cancer development and progression, CEACAM6 has become an attractive therapeutic or theragnostic target in a number of malignancies [13,29,30]. This line of investigation has been supported by in vitro observations that genetic downregulation of CEACAM6 results in decreased cellular invasiveness [23], reduction in the anoikis resistance and suppression of metastatic potential in cancer cells [31].…”

“…Because of its recognized role in cancer development and progression, CEACAM6 has become an attractive therapeutic or theragnostic target in a number of malignancies [ 13 , 29 , 30 ]. This line of investigation has been supported by in vitro observations that genetic downregulation of CEACAM6 results in decreased cellular invasiveness [ 23 ], reduction in the anoikis resistance and suppression of metastatic potential in cancer cells [ 31 ].…”

Prognostic value of the immune target CEACAM6 in cancer: a meta-analysis

“…[24][25][26][27][28][29]61 In addition, it could be used as a prognostic biomarker and some studies have evaluated the prognostic value of CEACAM6 serum levels in patients with cancer. [65][66][67] However, our study aimed to explore the prognostic role of CEACAM6 in human cancers, rather than in blood. With the potential role of CEACAM6 as immune checkpoint inhibitor in tumors, we focused this evaluation only on primary cancers.…”

A Phase 1, Open-Label, Dose-Escalation Study of L-DOS47 in Combination With Pemetrexed Plus Carboplatin in Patients With Stage IV Recurrent or Metastatic Nonsquamous NSCLC

“…CEACAM6 overexpression is generally associated with worse OS and DFS in a variety of solid tumors, 18 and serum CEACAM6 has been reported as a potential biomarker in pancreatic adenocarcinoma and plasma cell disorders. 19 , 20 , 21 In addition, Cao et al. 22 evaluated differentially expressed genes including CEACAM6 in peripheral blood exosomes as potential biomarkers for lung cancer; although the study was not quantitative, CEACAM6 exosome expression was higher in lung adenocarcinoma than in squamous cell carcinoma.…”