Zhao Haishan, Tang Hongtao, Xiao Qinghuan, He Miao, Zhao Lin, Fu Yingzi, Wu Huizhe, Yu Zhaojin, Jiang Qian, Yan Yuanyuan, Jin Feng, Wei Minjie
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
Mol Med Rep. 2016 Dec;14(6):5261-5270. doi: 10.3892/mmr.2016.5856. Epub 2016 Oct 19.
Cancer stem cells (CSCs) have been suggested to serve an important role in tumor recurrence and metastasis in breast cancer. The hedgehog (Hh) signaling pathway is essential for the maintenance of breast CSCs. The present study used immunohistochemistry to investigate the expression of Patched (PTCH) and Gli1, which are the main components of the Hh signaling pathway, as well as the expression of cluster of differentiation (CD)44/CD24, which are markers for breast CSCs, in 266 patients with breast cancer. The combined expression of PTCH and Gli1 was significantly associated with larger tumors (>2.0 cm; P=0.001), lymph node metastasis (P=0.003), invasive lobular carcinoma (P=0.016) and Grade II‑III tumors (P<0.001). In addition, PTCH and Gli1 expression was associated with lymph node metastasis (P=0.005 and P=0.001) and Grade II‑II tumors (P=0.020 and P=0.033) in breast cancer patients with the CD44+/CD24‑ phenotype. The expression of PTCH and Gli1 was also associated with significantly shorter overall survival and disease‑free survival (DFS) in breast cancer patients with the CD44+/CD24‑ phenotype. Multivariate Cox regression analysis demonstrated that PTCH expression and the CD44+/CD24‑ phenotype were independent prognostic factors for decreased DFS in patients with breast cancer. These findings suggest that the Hh signaling pathway in breast CSCs may contribute to the poor outcome of patients with breast cancer.
癌症干细胞（CSCs）被认为在乳腺癌的肿瘤复发和转移中起重要作用。刺猬（Hh）信号通路对于维持乳腺CSCs至关重要。本研究采用免疫组织化学方法，调查了266例乳腺癌患者中Hh信号通路的主要成分Patched（PTCH）和Gli1的表达，以及乳腺CSCs标志物分化簇（CD）44/CD24的表达。PTCH和Gli1的联合表达与较大肿瘤（>2.0 cm；P=0.001）、淋巴结转移（P=0.003）、浸润性小叶癌（P=0.016）和II-III级肿瘤（P<0.001）显著相关。此外，在CD44+/CD24-表型的乳腺癌患者中，PTCH和Gli1表达与淋巴结转移（P=0.005和P=0.001）以及II-II级肿瘤（P=0.020和P=0.033）相关。PTCH和Gli1的表达还与CD44+/CD24-表型的乳腺癌患者的总生存期和无病生存期（DFS）显著缩短相关。多变量Cox回归分析表明，PTCH表达和CD44+/CD24-表型是乳腺癌患者DFS降低的独立预后因素。这些发现表明，乳腺CSCs中的Hh信号通路可能导致乳腺癌患者预后不良。
