Details

Autor(en) / Beteiligte

• Pilgrim, Charles H.C
• Brettingham-Moore, Kate
• Pham, Alan
• Murray, William
• Link, Emma
• Smith, Marty
• Usatoff, Val
• Evans, Peter M
• Banting, Simon
• Thomson, Benjamin N
• Michael, Michael
• Phillips, Wayne A

Titel

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

Ist Teil von

• HPB (Oxford, England), 2011-11, Vol.13 (11), p.811-816

Ort / Verlag

Oxford, UK: Elsevier Ltd

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract 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.