Drug metabolism-related genes as potential biomarkers: analysis of expression in normal and tumour breast tissue.
The complex role of drug metabolism-related enzymes and their possible influence in cancer development, treatment and outcome has not yet been completely elucidated. There is evidence that these enzymes can activate certain environmental procarcinogens to more toxic derivatives and thus a role has been proposed for them in carcinogenesis. The fact that they can also inactivate a number of chemotherapeutic drugs has raised the possibility of these enzymes influencing the sensitivity of tumour cells to anticancer agents. In this report, we analyse the expression of drug metabolism-related genes within a whole genome microarray study of 104 breast cancer and 17 normal breast specimens. Kaplan-Meier survival curves, Chi-squared, and Cox Regression analyses were used to identify associations between expression of gene transcripts and patients' clinicopathological and survival data. Our results show that several of these genes are significantly expressed in both normal and tumour tissue; in many cases, expression is altered in the tumour specimens as compared to normal breast tissue. Moreover, expression of ARNT2 and GST A1 was correlated with prognosis. Kaplan-Meier analysis showed expression of ARNT2 mRNA to correlate significantly with favourable disease outcome for patients, in terms of both their disease-free survival (P = 0.0094) and overall survival (P = 0.0018) times from diagnosis, while detection of GST A1 mRNA correlated with shortened disease-free survival (P = 0.0131) and overall survival (P = 0.0028). Multivariate analysis indicated GST A1 expression to be an independent prognostic factor for overall survival (P = 0.045). Our results suggest a possible use of ARNT2 and GST A1 as prognostic breast cancer biomarkers.
Martinez
Vanesa
V
National Institute for Cellular Biotechnology (NICB), Dublin City University, Dublin 9, Ireland.
Kennedy
Susan
S
Doolan
Padraig
P
Gammell
Patrick
P
Joyce
Helena
H
Kenny
Elaine
E
Prakash Mehta
Jai
J
Ryan
Eoin
E
O'Connor
Robert
R
Crown
John
J
Clynes
Martin
M
O'Driscoll
Lorraine
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000096:biosynthesis*; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor / Q000032:analysis*; D001940:Breast; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D005982:Glutathione Transferase / Q000096:biosynthesis*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
D000970:Antineoplastic Agents; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; C490989:ARNT2 protein, human; C484555:GSTA1 protein, human