Genetic polymorphism and gene expression of microsomal epoxide hydrolase in non-small cell lung cancer.
Genetic polymorphisms of microsomal epoxide hydrolase (mEH) have been associated with increased risk of lung cancer. However, expression of mEH and its clinical significance in non-small cell lung cancer (NSCLC) have not been investigated. In this study we investigated the expression and genetic polymorphism of mEH in non-small cell lung cancer (NSCLC) patients. Genetic polymorphism was determined by restriction fragment length polymorphism of polymerase chain reaction (PCR) products. The allelic expression pattern as well as expression level of mEH were determined by reverse transcription-PCR (RT-PCR), cDNA sequencing, sequence alignment, immunoblotting and immunohistochemistry. Genotype distributions of mEH in Taiwan's NSCLC patients were 44.4% of 340TAC/340TAC, 48.6% of 340TAC/340CAC, and 7.0% of 340CAC/340CAC in exon 3, and 80.6% of 418CAT/418CAT, 19.4% of 418CAT/418CGT and 0% of 418CGT/418CGT in exon 4. Of the 72 NSCLC biopsies analyzed, mEH was expressed in 60 (83%) surgical specimens, and the major allelic expression pattern was fast type (Tyr113) in exon 3 (90.3%) and slow type (His139) in exon 4 (100%). Immunohistochemical staining showed that mEH was expressed in 326 of 423 (77.0%) tumor (lung tissue) specimens and in 48 of 93 (51.6%) metastatic lymph nodes. A significant difference in patient survival was found when mEH expression and adriamycin-containing chemotherapy were used to group patients (p=0.0167). In conclusion, with the combination of fast type (Tyr113) and slow type (His139), the mEH enzyme expressed in most NSCLC patients may have intermediate activity. Our findings indicate that with respect to cancer risk and disease progression, the expression level of mEH is as important as genetic polymorphism. In addition, mEH expression in NSCLC could be involved in drug resistance and prognosis of patients.
Lin
Torng-Sen
TS
Chang-Hua Christian Hospital, Department of Surgery, Chang-Hua, Taiwan, R.O.C.
Huang
Hsuan-Hua
HH
Fan
Yi-Hsin
YH
Chiou
Shiow-Her
SH
Chow
Kuan-Chih
KC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004851:Epoxide Hydrolases / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D004851:Epoxide Hydrolases