title: The Hedgehog signaling pathway is associated with poor prognosis in breast cancer patients with the CD44+/CD24‑ phenotype.
abstract: 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.
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Haishan
authors: H
authors: Zhao
authors: Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Hongtao
authors: H
authors: Tang
authors: Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Qinghuan
authors: Q
authors: Xiao
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Miao
authors: M
authors: He
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Lin
authors: L
authors: Zhao
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Yingzi
authors: Y
authors: Fu
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Huizhe
authors: H
authors: Wu
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Zhaojin
authors: Z
authors: Yu
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Qian
authors: Q
authors: Jiang
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Yuanyuan
authors: Y
authors: Yan
authors: Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Feng
authors: F
authors: Jin
authors: Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110122, P.R. China.
authors: Minjie
authors: M
authors: Wei
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D053823:Hedgehog Proteins; D018960:Hyaluronan Receptors