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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 2011 International Hepato-Pancreato-Biliary Association
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 Type:||Refereed Article|
|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)|
|Web of Science® Times Cited:||10|
|Deposited By:||Menzies Institute for Medical Research|
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