Expression and clinical significance of carcinoembryonic antigen-related cell adhesion molecule 6 in breast cancers

Abstract

Carcino-embryonic antigen-related cell adhesion molecule 6 (CEACAM6), one of the members of human carcino-embryonic antigens, is a multifunctional regulatory protein involved in various cellular processes in cancers. Its role in malignant transformation and the clinical significance has been extensively studied in colonic and pancreatic cancers. However, relatively few studies have been done on breast cancers. In the current study, CEACAM6 expression in two independent cohorts of invasive breast cancers were evaluated immunohistochemically and correlated with clinico-pathological features, biomarker profiles and patient survival. In the primary cohort, CEACAM6 expression was detected in 37.1 % (312/840) of primary invasive cancers. It was positively correlated with HER2 (p < 0.001). Concordantly, HER2-OE subtype showed the highest CEACAM6 expression (62.7 %) among all molecular subtypes; whereas, other subtypes also showed substantial CEACAM6 expression (21.8-37.5 %). Interestingly, a significantly worse overall survival was found in high pN stage HER2 positive cancers with CEACAM6 positivity (log-rank = 4.452, p = 0.035) and this could be validated in an independent cohort. Additionally, HER2 signaling was found to induce SMAD3 phosphorylation and CEACAM6 expression in a cell line model. Likewise, in the primary tumors, a positive association was found between HER2 and SMAD3 phosphorylation in CEACAM6 positive cancers (p = 0.012). Overall, CEACAM6 was widely expressed in different molecular subtypes, but highest and significantly in HER2-OE breast cancer. Within this group, CEACAM6 was associated with adverse high nodal stage patient outcome. Given the wide expression of CEACAM6 in all breast cancers, its roles as prognostic marker and therapeutic target warrant further evaluation.

Emerging Role and Targeting of Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACAM6) in Human Malignancies

“…In a cohort of 840 primary invasive breast cancers and a separate validation cohort of 300 invasive breast cancers CEACAM6 expression was found to be present in 37.1% (312/840 pts) cases [47]. In the validation cohort, CEACAM6 expression was highest in the HER2+ tumors (67%) and lowest in triple negative breast cancer (TNBC) (25%).…”

Long-term exposure of MCF-7 breast cancer cells to ethanol stimulates oncogenic features

“…A consistent pattern of changes induced by long-term ethanol, but not acetaldehyde, is the correlation between the upregulation of the key stem cell proteins Oct4a and Nanog (67) and an important cancer marker, Ceacam6 (50), in addition to the induction of anchorage-independence evidenced by soft agar growth. OCT4 is well known as a key gene responsible for the stemness network, and the main factor in the generation of induced pluripotent stem cells (iPS).…”

“…In view of the interesting results on the transcriptional expression of the malignancy related CEACAMs, we evaluated by western blot analysis the effects of long-term ethanol exposure on Ceacam6, an oncogenic protein associated with breast cancer (50), along with the Oct4 and Nanog proteins. Fig.…”

Current status of the prognostic molecular biomarkers in breast cancer: A systematic review

“…CEACAM6 has also been associated with invasive and treatment-resistant breast cancer (28). However, in a large-scale cohort study, CEACAM6 expression in luminal breast cancer exhibited no effect on OS or correlation with prognosis, although an association between CEACAM6 expression and prognosis in breast cancer overexpressing HER2 was revealed, as the high expression group tended to exhibit poorer OS (28 demonstrated an improved DFS compared with patients exhibiting the PIK3CA mutations. The prognosis for HER2-positive patients with PIK3CA mutations treated with trastuzumab was significantly worse than for patients exhibiting the wild-type variation, which is considered to occur since the P13K/protein kinase B pathway is adversely affected by PIK3CA mutations, resulting in the lower efficacy of trastuzumab.…”

“…CEACAM6 expression in atypical ductal hyperplasia has been suggested to serve an important role in the development of breast cancer (27). CEACAM6 has also been associated with invasive and treatment-resistant breast cancer (28). However, in a large-scale cohort study, CEACAM6 expression in luminal breast cancer exhibited no effect on OS or correlation with prognosis, although an association between CEACAM6 expression and prognosis in breast cancer overexpressing HER2 was revealed, as the high expression group tended to exhibit poorer OS (28 demonstrated an improved DFS compared with patients exhibiting the PIK3CA mutations.…”