CD109 is a potential target for triple-negative breast cancer

Abstract

The aim of this study is to explore the expression of CD109 in breast cancer stem cells and the relationship between CD109 protein and clinicopathological characteristics of breast cancer. CD44+/CD24- tumor cells (CSCs) were selected by flow cytometry. The protein expression of CD109 was analyzed by immunohistochemistry staining, and the relationship between CD109 and clinicopathological parameters of breast cancer was determined. CD109 positively regulated the proliferation of breast CSCs in vitro, and CD109 protein expression was significantly higher in triple-negative breast cancer (TNBC) compared to non-TNBC (63.78 vs. 3.71 %, P = 0.001). Moreover, CD109 protein expression was related to the histological grade of breast cancer (P = 0.015), whereas age (P = 0.731), tumor size (P = 0.995), clinical stage (P = 0.644), and lymph node metastasis (P = 0.924) were not. In the logistic regression model, histological grade (P = 0.001) and molecular type (P = 0.001) were significantly related to CD109 expression. The patients with high expression of CD109 protein had significantly poorer postoperative disease-specific survival than those with no or low expression of CD109 protein (P = 0.001). In the Cox regression, CD109 was an independent prognostic factor (P = 0.001). CD109 is highly expressed in TNBC and is a potential biomarker for the initiation, progression, and differentiation of breast cancer tumors.

CD109: a multifunctional GPI‐anchored protein with key roles in tumor progression and physiological homeostasis

“…Previous reports (Table ) and our analyses using The Cancer Genome Atlas (TCGA) (http://cancergenome.nih.gov/) demonstrate that patients with higher expression of CD109 (CD109‐high) have a significantly worse prognosis than those with lower expression of CD109 (CD109‐low) in various malignant tumors, such as those associated with glioma, glioblastoma, breast ductal carcinoma, lung, gastric, colorectal, and pancreatic adenocarcinomas, as well as urothelial carcinoma of the urinary bladder, hepatocellular carcinoma, epithelioid sarcoma, myxofibrosarcoma, and diffuse large B‐cell lymphoma (Table and Fig. ) . A controversial exception is urothelial carcinoma of the urinary bladder, where CD109 expression inversely correlated with poor prognosis in patients in our study (Table ) .…”

“…We previously reported that CD109‐deficient mice exhibit epidermal hyperplasia in skin and osteopenia in bone, suggesting possible CD109‐related physiological functions in vivo. Although previous studies report CD109 expression in various malignant tumors and correlation with prognosis in patients harboring a malignant tumor, such as a glioblastoma or lung adenocarcinoma, its roles in human disease remain largely unknown. In this review, we describe our views and perspectives on the significance of CD109 in malignant tumors and provide a description of our recent studies showing the involvement of CD109 in skin and bone‐tissue homeostasis in CD109‐deficient mice.…”

“…High levels of CD109 expression have been detected in various tumor‐cell lines and tumor tissues, including those associated with squamous cell carcinomas (SCCs) of the lung, esophagus, uterus, and oral cavity, adenocarcinomas of the lung and pancreas, breast cancer, glioblastoma, hepatocellular carcinoma, urothelial carcinoma of the urinary bladder, and several types of sarcomas (Table ) . Immunohistochemical (IHC) analyses revealed elevated CD109 expression on tumor cells (Fig.…”

CD109 is identified as a potential nasopharyngeal carcinoma biomarker using aptamer selected by cell-SELEX

“…It was reported that oral SCC with the over-expression of CD109 exhibited accelerated cell growth, and CD109-positive oral dysplastic lesions showed a predisposition to progress to SCC in three years [36]. In addition, a strong correlation was detected between CD109 expression and prognosis in soft tissue sarcomas and TNBC [37]. These data suggest that CD109 expression may be associated with the pathogenesis and prognosis of several human tumors.…”

“…Recently, some researchers suggested that high expression of CD109 regulates the phenotype of cancer stem-like cells/cancer-initiating cells (CSCs/CICs) in the novel epithelioid sarcoma cell line ESX and may be a CSCs/CICs biomarker in epithelioid sarcoma [38]. In another study, Tao et al also reported that CD109 was over-expressed in breast CSCs [37]. Tumor sphere is one of the methods to enrich CSCs.…”