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骨髓瘤肿瘤的基于通路的网络分析:意义未明的单克隆丙种球蛋白病、冒烟型多发性骨髓瘤和多发性骨髓瘤。

Pathway-based network analysis of myeloma tumors: monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and multiple myeloma.

作者信息

Dong L, Chen C Y, Ning B, Xu D L, Gao J H, Wang L L, Yan S Y, Cheng S

机构信息

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, China.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, China

出版信息

Genet Mol Res. 2015 Aug 14;14(3):9571-84. doi: 10.4238/2015.August.14.20.

Abstract

Although many studies have been carried out on monoclonal gammopathy of unknown significances (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM), their classification and underlying pathogenesis are far from elucidated. To discover the relationships among MGUS, SMM, and MM at the transcriptome level, differentially expressed genes in MGUS, SMM, and MM were identified by the rank product method, and then co-expression networks were constructed by integrating the data. Finally, a pathway-network was constructed based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and the relationships between the pathways were identified. The results indicated that there were 55, 78, and 138 pathways involved in the myeloma tumor developmental stages of MGUS, SMM, and MM, respectively. The biological processes identified therein were found to have a close relationship with the immune system. Processes and pathways related to the abnormal activity of DNA and RNA were also present in SMM and MM. Six common pathways were found in the whole process of myeloma tumor development. Nine pathways were shown to participate in the progression of MGUS to SMM, and prostate cancer was the sole pathway that was involved only in MGUS and MM. Pathway-network analysis might provide a new indicator for the developmental stage diagnosis of myeloma tumors.

摘要

尽管针对意义未明的单克隆丙种球蛋白病(MGUS)、冒烟型多发性骨髓瘤(SMM)和多发性骨髓瘤(MM)已经开展了许多研究,但其分类及潜在发病机制仍远未阐明。为了在转录组水平发现MGUS、SMM和MM之间的关系,采用秩乘积法鉴定了MGUS、SMM和MM中差异表达的基因,然后整合数据构建共表达网络。最后,基于京都基因与基因组百科全书通路富集分析构建通路网络,并确定通路之间的关系。结果表明,MGUS、SMM和MM的骨髓瘤肿瘤发展阶段分别涉及55、78和138条通路。其中鉴定出的生物学过程与免疫系统密切相关。与DNA和RNA异常活性相关的过程和通路在SMM和MM中也存在。在骨髓瘤肿瘤发展的全过程中发现了6条共同通路。9条通路参与了MGUS向SMM的进展,而前列腺癌是仅在MGUS和MM中涉及的唯一通路。通路网络分析可能为骨髓瘤肿瘤发展阶段的诊断提供新的指标。

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