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四种癌症顺铂耐药中涉及的基因表达谱和致癌途径的差异。

Differences in gene expression profiles and carcinogenesis pathways involved in cisplatin resistance of four types of cancer.

机构信息

Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Capital Medical University, Beijing 100069, PR China.

出版信息

Oncol Rep. 2013 Aug;30(2):596-614. doi: 10.3892/or.2013.2514. Epub 2013 Jun 3.

Abstract

Cisplatin-based chemotherapy is the standard therapy used for the treatment of several types of cancer. However, its efficacy is largely limited by the acquired drug resistance. To date, little is known about the RNA expression changes in cisplatin-resistant cancers. Identification of the RNAs related to cisplatin resistance may provide specific insight into cancer therapy. In the present study, expression profiling of 7 cancer cell lines was performed using oligonucleotide microarray analysis data obtained from the GEO database. Bioinformatic analyses such as the Gene Ontology (GO) and KEGG pathway were used to identify genes and pathways specifically associated with cisplatin resistance. A signal transduction network was established to identify the core genes in regulating cancer cell cisplatin resistance. A number of genes were differentially expressed in 7 groups of cancer cell lines. They mainly participated in 85 GO terms and 11 pathways in common. All differential gene interactions in the Signal-Net were analyzed. CTNNB1, PLCG2 and SRC were the most significantly altered. With the use of bioinformatics, large amounts of data in microarrays were retrieved and analyzed by means of thorough experimental planning, scientific statistical analysis and collection of complete data on cancer cell cisplatin resistance. In the present study, a novel differential gene expression pattern was constructed and further study will provide new targets for the diagnosis and mechanisms of cancer cisplatin resistance.

摘要

基于顺铂的化疗是治疗多种癌症的标准疗法。然而,其疗效在很大程度上受到获得性耐药性的限制。迄今为止,人们对顺铂耐药性癌症中的 RNA 表达变化知之甚少。鉴定与顺铂耐药性相关的 RNA 可能为癌症治疗提供特定的见解。在本研究中,使用从 GEO 数据库获得的寡核苷酸微阵列分析数据对 7 种癌细胞系进行了表达谱分析。使用基因本体 (GO) 和 KEGG 途径等生物信息学分析来鉴定与顺铂耐药性特异性相关的基因和途径。建立了信号转导网络来鉴定调节癌细胞顺铂耐药性的核心基因。在 7 组癌细胞系中,有许多基因差异表达。它们主要参与 85 个 GO 术语和 11 个共同途径。对信号网络中的所有差异基因相互作用进行了分析。CTNNB1、PLCG2 和 SRC 是变化最显著的。通过使用生物信息学,通过彻底的实验规划、科学的统计分析和收集完整的癌细胞顺铂耐药性数据,从微阵列中检索和分析大量数据。在本研究中,构建了一种新的差异基因表达模式,进一步的研究将为癌症顺铂耐药性的诊断和机制提供新的靶点。

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