title: Reduced expression of semaphorin 4D and plexin-B in breast cancer is associated with poorer prognosis and the potential linkage with oestrogen receptor.
abstract: Involvement of semaphorin 4D (Sema4D) and the receptor proteins of the plexins B family (plexin-B1, -B2 and -B3) in solid tumours suggests they play a role in breast cancer. In the present study, the expression of Sema4D and plexin-Bs was examined in a breast cancer cohort. The expression of Sema4D and plexin-Bs was examined in 147 tumours together with 22 normal mammary tissues using quantitative PCR along with clinicopathological patient data, as well as in MCF-7 and MDA-MB-231 cell lines treated with selective oestrogen receptor modulators (SERMs). The expression of Sema4D, plexin-B1 and -B2 was markedly reduced in tumours with local recurrence, compared to the patients that remained disease-free. The reduced Sema4D expression was associated with poorer disease-free survival (median, 111.6 months, 95% CI, 96.5-126.7), compared to the patients with a higher expression (median, 144.0 months; 95% CI, 130.8-157.3; p=0.033). A reduced expression of plexin-B1 was observed in tumours with poorer differentiation and was associated with poorer overall and disease-free survival. No similar association was identified in relation to plexin-B2 and -B3. A higher expression of Sema4D and plexin-B1 was observed in the ERα-positive tumours compared to the ERα-negative tumours. The expression of these molecules was largely regulated in breast cancer cells exposed to SERMs. A decreased expression of Sema4D, plexin-B1 and -B2 was associated with local recurrence and poor prognosis. Response to SERMs indicated potential perspectives of these molecules in clinical assessment and management of diseases.
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
authors.forename: Muhammad Faraz Arshad
authors.initials: MF
authors.lastname: Malik
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.affiliation: Metastasis and Angiogenesis Research Group, Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010636:Phenols / Q000494:pharmacology; D011379:Prognosis; D011720:Pyrazoles / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000235:genetics*; D039961:Semaphorins / Q000235:genetics*
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; C000604175:PLXNB2 protein, human; D010636:Phenols; D011720:Pyrazoles; D011956:Receptors, Cell Surface; D039961:Semaphorins; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol