The expression levels of CYP3A4 and CYP3A5 serve as potential prognostic biomarkers in lung adenocarcinoma

Abstract

Lung adenocarcinoma remains to be a high-mortality disease with few effective prognostic biomarkers. Novel biomarkers are urgently demanded to supplement the current prognostic biomarkers. Here, we explored the prognostic value of CYP3A4 and CYP3A5 in lung adenocarcinoma. The tissue microarray was made up of lung adenocarcinoma samples and corresponding normal lung tissues from Nanjing Medical University affiliated Cancer Hospital Tissue Bank. The expression of CYP3A4, together with CYP3A5, was detected by the chip data from Gene Expression Omnibus datasets and immunohistochemistry staining of the tissue microarray. Then, we assessed the relationships between CYP3A4 or CYP3A5 expression level and clinicopathological factors to estimate the clinical significance. Kaplan–Meier curves were applied to analyze the prognosis. Univariate and multivariate Cox analyses were subsequently applied to identify the independent prognostic factors. Immunohistochemistry staining results showed that by comparison with matched normal tissues, CYP3A4 was frequently hyper-expressed in lung adenocarcinoma tissues while CYP3A5 was hypo-expressed, which was consistent with the Gene Expression Omnibus analysis. Kaplan–Meier analysis indicated that high-CYP3A4 or low-CYP3A5 expression level predicted poor survival in lung adenocarcinoma patients. Multivariate Cox analysis found that hypo-expression of CYP3A5 was an independent prognostic factor. Further study revealed that combination of these two markers exhibited a more powerful predictor of poor prognosis, which could target to more accurate survival of lung adenocarcinoma. Our findings indicate that combination of CYP3A4 and CYP3A5 may serve as a novel prognostic biomarker in lung adenocarcinoma, which contribute to the precision of predicting the survival in lung adenocarcinoma.