The expression levels of CYP3A4 and CYP3A5 serve as potential prognostic biomarkers in lung adenocarcinoma
The expression levels of CYP3A4 and CYP3A5 serve as potential prognostic biomarkers in lung adenocarcinoma
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CYP3A4和CYP3A5的表达水平可作为肺腺癌的潜在预后生物标志物
DOI：
10.1177/1010428317698340
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发表时间：
2017-04-01
期刊：
影响因子：
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通讯作者：
Wang Jun
中科院分区：
文献类型：
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作者：
Mao Qixing;Xu Juqing;Wang Jun
肺腺癌仍是一种高死亡率疾病，有效的预后生物标志物很少。迫切需要新的生物标志物来补充现有的预后生物标志物。本文探讨了CYP 3A 4和CYP 3A 5在肺腺癌预后中的价值。组织芯片由南京医科大学附属肿瘤医院组织库的肺腺癌标本和相应的正常肺组织组成。通过基因表达Omnibus数据集的芯片数据和组织芯片的免疫组织化学染色检测CYP 3A 4和CYP 3A 5的表达。然后，我们评估CYP 3A 4或CYP 3A 5表达水平与临床病理因素的关系，以估计临床意义。Kaplan-Meier曲线分析预后。单因素和多因素考克斯分析随后被应用于确定独立的预后因素。免疫组化染色结果显示，与正常肺组织相比，肺腺癌组织中CYP 3A 4高表达，CYP 3A 5低表达，与基因表达谱分析结果一致。Kaplan-Meier分析显示，CYP 3A 4高表达或CYP 3A 5低表达均预示着肺腺癌患者生存率低。多因素考克斯分析发现，CYP 3A 5低表达是独立的预后因素。进一步的研究表明，这两种标志物的联合显示出更强的预后不良的预测，这可能是更准确的肺腺癌的生存目标。我们的研究结果表明，CYP 3A 4和CYP 3A 5的组合可能作为一种新的预后生物标志物在肺腺癌，这有助于预测肺腺癌的生存的精确度。
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.