Clinical Implications of Stem Cell Gene Oct-4 Expression in ... : Annals of Surgery (original) (raw)

Original Articles

Liu, Cai-gang MD*; Lu, Ying MD†; Wang, Bin-bin PhD*; Zhang, Yan-jun PhD*; Zhang, Rui-shan PhD*; Lu, Yang PhD*; Chen, Bo MD*; Xu, Huimian MD*; Jin, Feng MD*; Lu, Ping MD, PhD*

*Department of Breast Surgery, General surgery, the first hospital of China Medical University, Shenyang, China; and

†Canada Catherine Biotech Company Co., Ltd. 34 Comrie Terr., Toronto, Canada.

Reprints: Ping Lu, MD, PhD, Department of Breast Surgery, First Affiliated Hospital of China Medial University, Heping, Shenyang, Liaoning Province 110001, China. E-mail: [email protected].

The study was funded by the China National Natural Science Foundation (No. 30772100).

No competing interests are declared by any of the authors.

Purpose:

To explore the expression of stem cell genes in breast cancer and the relationship between stem cell gene expression and clinical and pathological characteristics and prognosis of breast cancer.

Background:

By now, stem cell differentiation-related genes and the relationship between the genes and clinic-pathological characteristics and prognosis of breast cancer are still unclear.

Materials and Methods:

CD44+/CD24− tumor cells were selected by Flow cytometry. The differential expression of genes between CD44+/CD24− tumor cells and non-CD44+/CD24− tumor cells were detected by RT2 Profiler™ PCR Array. The expression of stem cell gene Octamer-4 (Oct-4) was analyzed by immunohistochemistry staining and the relationship between Oct-4 and clinicopathological parameters of breast cancer was determined.

Results:

Seven different genes including stem cell differentiation-related factors (CD44, Oct-4, and nestin), cell cycle regulators (APC and CDC2), and growth factors (HGF and TGF) were detected as significantly differently expressed between CD44+/CD24− tumor cells and non-CD44+/CD24− tumor cells. Oct-4 protein expressed significantly higher in cancerous tissues than adjacent-tumor tissues (P = 0.001). Moreover, we observed that the expression of Oct-4 protein was related to histological type, lymph node status and molecular type of breast cancer (P = 0.001, 0.006, and 0.001, respectively). After survival analysis, the cases with highly expressed Oct-4 protein attained a significantly poorer postoperative disease-specific survival than those with none/low expressed Oct-4 protein (P = 0.001). In the Cox regression test, tumor size, histological type, disease stage, lymph node metastasis, Her-2 and Oct-4 were detected as the independent prognostic factors (P = 0.031, 0.012, 0.001, 0.002, 0.030, and 0.003, respectively).

Conclusions:

Oct-4 was highly expressed in CD44+/CD24− tumor cells, and may be a potential biomarker for the initiation, progression, and differentiation of breast cancer.