title: Thioredoxin interacting protein and its association with clinical outcome in gastro-oesophageal adenocarcinoma.
abstract: The overall prognosis for operable gastro-oesophageal adenocarcinoma remains poor and therefore neoadjuvant chemotherapy has become the standard of care, in addition to radical surgery. Certain anticancer agents (e.g. anthracyclines and cisplatin) generate damaging reactive oxygen species as by-products of their mechanism of action. Drug effectiveness can therefore depend upon the presence of cellular redox buffering systems that are often deregulated in cancer. The expression of the redox protein, thioredoxin interacting protein, was assessed in gastro-oesophageal adenocarcinomas. Thioredoxin interacting protein expression was assessed using conventional immunohistochemistry on a tissue microarray of 140 adenocarcinoma patients treated by primary surgery alone and 88 operable cases treated with neoadjuvant chemotherapy. In the primary surgery cases, high thioredoxin interacting protein expression associated with a lack of lymph node involvement (p=0.005), no perineural invasion (p=0.030) and well/moderate tumour differentiation (p=0.033). In the neoadjuvant tumours, high thioredoxin interacting protein expression was an independent marker for improved disease specific survival (p=0.002) especially in cases with anthracycline-based regimes (p=0.008). This study highlights the potential of thioredoxin interacting protein as a biomarker for response in neoadjuvant treated gastro-oesophageal adenocarcinoma and may represent a useful therapeutic target due to its association with tumour progression.
authors.affiliation: Academic Unit of Oncology, School of Molecular Medical Sciences, University of Nottingham, Nottingham University Hospitals, Nottingham NG5 1PB, UK.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Woolston
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Madhusudan
authors.forename: Irshad N
authors.initials: IN
authors.lastname: Soomro
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Lobo
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Reece-Smith
authors.forename: Simon L
authors.initials: SL
authors.lastname: Parsons
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Martin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000008:administration & dosage* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D017382:Reactive Oxygen Species; C486715:TXNIP protein, human
keywords: Chemotherapy; Gastric cancer; Predictive; Prognostic; Redox; Thioredoxin interacting protein
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