Incorporating cytochrome P450 3A4 genotype expression and FT-IR/Raman spectroscopy data as means of identification of breast tumors.
We have evaluated the use of cytochrome P450 (CYP), 3A4 genotype and Fourier transform-infrared (RT-IR)/Raman spectroscopy as diagnostic tools for detection of breast tumors. CYP is involved in catalytic activity of oxidative metabolism of many chemicals in fatty tissues, and it plays a major role in biotransformation and detoxication of environmental contaminants. FT-IR and Raman spectroscopy have been used to develop methods for cancer assessment. Thus, the hypothesis was that a) CYP 3A4 gene expression level may have effect on the clinical presentation of breast cancer; and b) a combination spectroscopy and genotype analysis may strengthen the level of diagnosis. In parallel studies we compared by reverse-transcription-polymerase chain reaction (RT-PCR), the CYP 3A4 mRNA transcript levels, and by FT-IR the pathology of breast tissues. RNA was isolated from human breast biopsies and cultured tumor cells (MCF-7). A comparison of the levels of RT-PCR was made between CYP 3A4 genotype and 1B1, a genotype associated with human tumors, testing 3 normal breast tissues, 2 specimen from breast reduction and 7 breast tumors. Two variants of CYP 3A4 mRNA were observed, of which a 380-bp was displayed in 4 out of 5 pathologically determined tumors, and a 260-bp fragment was associated with normal tissues. The predictive value of the CYP 3A4 for the detection of tumor tissues was greater than that observed with the CYP 1B1. FT-IR signal patterns were distinct for tumor tissues as compared with that of normal tissue. Our findings demonstrated the importance of CYP 3A4 as molecular biomarker for determining the presence of breast tumors. This data in association with FT-IR/Raman spectroscopy and pathology, it can be an ideal test for predicting the clinical presentation of breast cancer.
Departments of Surgery and Pathology, University of Mississippi Medical Center, Departments of Biology and Chemistry, Jackson State University, Jackson, Mississippi, USA.
Spencer O
SO
Miller
Gideon P
GP
Ewing
Carol
C
Howard
Hiroyasu
H
Tachikawa
Steven A
SA
Bigler
W Henry
WH
Barber
Michael
M
Angel
D Olga
DO
McDaniel
D014408:Biomarkers, Tumor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000737:chemistry / Q000175:diagnosis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A