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

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.

Microarray analyses reveal genes related to progression and prognosis of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is a high morbidity and mortality cancer in China. Here are few biomarkers and therapeutic targets. Our study was aimed to identify candidate genes correlated to ESCC. Oncomine, The Cancer Genome Atlas, Gene Expression Omnibus were retrieved for eligible ESCC data. Deregulated genes were identified by meta-analysis and validated by an independent dataset. Survival analyses and bioinformatics analyses were used to explore potential mechanisms. Copy number variant analyses identified upstream mechanisms of candidate genes. In our study, top 200 up/down-regulated genes were identified across two microarrays. A total of 139 different expression genes were validated in GSE53625. Survival analysis found that nine genes were closely related to prognosis. Furthermore, Gene Ontology analyses and Kyoto Encyclopedia of Genes and Genomes analyses showed that different expression genes were mainly enriched in cell division, cell cycle and cell-cell adhesion pathways. Copy number variant analyses indicated that overexpression of ECT2 and other five genes were correlated with copy number amplification. The current study demonstrated that ECT2 and other eight candidate genes were correlated to progression and prognosis of esophageal squamous cell carcinoma, which might provide novel insights to the mechanisms.

Predictive Value of Ercc1 and Xpd Polymorphisms for Clinical Outcomes of Patients Receiving Neoadjuvant Therapy: A Prisma-Compliant Meta-Analysis.

Excision repair cross complementing 1 (ERCC1) and xeroderma pigmentosum group D (XPD) play important roles in the nucleotide excision repair (NER) pathway. The correlation between ERCC1 polymorphisms (rs11615 and rs3212986) and XPD polymorphisms (rs13181 and rs1799793) with the response rate and overall survival of cancer patients who accept neoadjuvant therapy has been extensively investigated. However, the results are inconclusive. In this study, we performed a meta-analysis to determine the strength of this correlation. A comprehensive literature search was conducted in Medline, PubMed, and Embase up to February 2015. A review of all titles and abstracts was performed by 2 of the authors to screen the articles based on the eligibility criteria. Clinical trials, observational studies, and epidemiological studies describing ERCC polymorphisms and neoadjuvant treatment were considered for review. The response rate was analyzed using pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Overall survival was assessed using the hazard ratio (HR) with corresponding 95% confidence intervals. In the present meta-analysis, we demonstrated that the ERCC1 rs3212986 polymorphism was significantly correlated with the response rate of esophageal cancer patients to neoadjuvant therapy (OR =  .49, 95% CI = 0.31-0.76, heterogeneity P = 0.480). Furthermore, a considerable correlation was observed between ERCC1 rs11615 and the response rate of esophageal cancer patients to neoadjuvant therapy (OR = 0.228, 95% CI = 0.125-0.418, heterogeneity P = 0.291). No correlation was observed in the meta-analysis of overall survival. The individual studies included in our study differed in their patient selection and therapeutic protocols, which might lead to some bias in the results. These findings indicate that the ERCC1 rs11615 and ERCC1 rs312986 polymorphisms may be candidate pharmacogenomic factors capable of predicting the response rate of esophageal cancer patients who accept neoadjuvant therapy. Further studies are warranted.