10779/rcsi.10789130.v1
Mary-Clare Cathcart
Mary-Clare
Cathcart
Kathy Gately
Kathy
Gately
Robert Cummins
Robert
Cummins
Elaine W. Kay
Elaine W.
Kay
Kenneth J. O'Byrne
Kenneth J.
O'Byrne
Graham P. Pidgeon
Graham P.
Pidgeon
Examination of thromboxane synthase as a prognostic factor and therapeutic target in non-small cell lung cancer.
Royal College of Surgeons in Ireland
2019
Adenocarcinoma
Apoptosis
Blotting
Western
Carcinoma
Non-Small-Cell Lung
Cell Line
Tumor
Cell Proliferation
Cyclooxygenase 2
Enzyme Inhibitors
Female
Gene Expression Regulation
Enzymologic
Neoplastic
Humans
Immunohistochemistry
Lung Neoplasms
Male
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
Thromboxane B2
Thromboxane-A Synthase
Tissue Array Analysis
Pathology
2019-11-22 16:50:07
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/Examination_of_thromboxane_synthase_as_a_prognostic_factor_and_therapeutic_target_in_non-small_cell_lung_cancer_/10789130
<p>BACKGROUND: Thromboxane synthase (TXS) metabolises prostaglandin H2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression has been reported in a range of cancers, and associated with a poor prognosis. TXS inhibition induces cell death in-vitro, providing a rationale for therapeutic intervention. We aimed to determine the expression profile of TXS in NSCLC and if it is prognostic and/or a survival factor in the disease.</p>
<p>METHODS: TXS expression was examined in human NSCLC and matched controls by western analysis and IHC. TXS metabolite (TXB2) levels were measured by EIA. A 204-patient NSCLC TMA was stained for COX-2 and downstream TXS expression. TXS tissue expression was correlated with clinical parameters, including overall survival. Cell proliferation/survival and invasion was examined in NSCLC cells following both selective TXS inhibition and stable TXS over-expression.</p>
<p>RESULTS: TXS was over-expressed in human NSCLC samples, relative to matched normal controls. TXS and TXB2 levels were increased in protein (p < 0.05) and plasma (p < 0.01) NSCLC samples respectively. TXS tissue expression was higher in adenocarcinoma (p < 0.001) and female patients (p < 0.05). No significant correlation with patient survival was observed. Selective TXS inhibition significantly reduced tumour cell growth and increased apoptosis, while TXS over-expression stimulated cell proliferation and invasiveness, and was protective against apoptosis.</p>
<p>CONCLUSION: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype. Inhibition of this enzyme inhibits proliferation and induces apoptosis. Targeting thromboxane synthase alone, or in combination with conventional chemotherapy is a potential therapeutic strategy for NSCLC.</p>