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MRNA gene expression correlates with histologically diagnosed chemotherapy-induced hepatic injury


Pilgrim, CHC and Brettingham-Moore, KH and Pham, A and Murray, W and Link, E and Smith, M and Usatoff, V and Evans, PM and Banting, S and Thomson, BN and Michael, M and Phillips, WA, MRNA gene expression correlates with histologically diagnosed chemotherapy-induced hepatic injury, HPB, 13, (11) pp. 811-816. ISSN 1365-182X (2011) [Refereed Article]

Copyright Statement

Copyright 2011 International Hepato-Pancreato-Biliary Association

DOI: doi:10.1111/j.1477-2574.2011.00365.x


INTRODUCTION: Chemotherapy-induced hepatic injuries (CIHI) are an increasing problem facing hepatic surgeons. It may be possible to predict the risk of developing CIHI by analysis of genes involved in the metabolism of chemotherapeutics, previously established as associated with other forms of toxicity.

METHODS: Quantitative reverse transcriptase-polymerase chain reaction methodology (q-RT-PCR) was employed to quantify mRNA expression of nucleotide excision repair genes ERCC1 and ERCC2, relevant in the neutralization of damage induced by oxaliplatin, and genes encoding enzymes relevant to 5-flurouracil metabolism, [thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD)] in 233 hepatic resection samples. mRNA expression was correlated with a histopathological injury scored via previously validated methods in relation to steatosis, steatohepatitis and sinusoidal obstruction syndrome.

RESULTS: Low-level DPD mRNA expression was associated with steatosis [odds ratio (OR) = 3.95, 95% confidence interval (CI) = 1.53-10.19, P < 0.003], especially when stratified by just those patients exposed to chemotherapy (OR = 4.48, 95% CI = 1.31-15.30 P < 0.02). Low expression of ERCC2 was associated with sinusoidal injury (P < 0.001). There were no further associations between injury patterns and target genes investigated.

CONCLUSIONS: Predisposition to the development of CIHI may be predictable based upon individual patient expression of genes encoding enzymes related to the metabolism of chemotherapeutics.

Item Details

Item Type:Refereed Article
Keywords:mRNA, chemotherapy
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Cancer genetics
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the health sciences
UTAS Author:Brettingham-Moore, KH (Dr Kate Brettingham-Moore)
ID Code:95845
Year Published:2011
Web of Science® Times Cited:10
Deposited By:Menzies Institute for Medical Research
Deposited On:2014-10-09
Last Modified:2017-11-06

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