Huang Chen, Nie Fangfei, Qin Zelian, Li Bolun, Zhao Xia
Department of Plastic Surgery, Peking University Third Hospital, Beijing, China.
Am J Dermatopathol. 2013 Feb;35(1):64-73. doi: 10.1097/DAD.0b013e31825ba13f.
The aim of this study was to examine the gene expression signatures of 2 types of excessive scarring, keloid and hypertrophic scar (HS), through the integrated bioinformatics analysis of multiple published gene expression profile datasets.
A literature search of microarray data published in focusing on keloid and HS was performed. The microarray data were reanalyzed to identify the common significantly dysregulated (CSD) genes. The experimental and statistical parameters of the studies were systematically evaluated to reveal any influences on the consensus findings among the studies. Overrepresentation analysis of gene ontology (GO) categories and pathways was used to explore the significantly dysregulated genes functionally associated with the pathogenesis of excessive scarring.
Seven published microarray studies on keloid and 4 studies on HS were identified. A total of 64 CSD genes were identified in keloid; 9 upregulated CSD genes were identified in HS. The 48 consistently dysregulated genes that overlapped in least 1 keloid study and 1 HS study were defined as the CSD genes in excessive scarring. The differences in the variables associated with the study protocols and data management were systematically documented and evaluated. Activated GO categories and pathways related to skeletal development, binding, extracellular matrix-receptor interaction, and adhesion were found to have significance in excessive scarring, implying a common pathological basis for keloid and HS formation. Notably, the GO categories related to cancer and the TGF-beta signaling pathway were significantly enriched in keloids.
As gene signatures and molecular markers of excessive scarring, the identified CSD genes may be particularly relevant to disease pathogenesis and serve as new therapeutic targets.
本研究旨在通过对多个已发表的基因表达谱数据集进行综合生物信息学分析，研究瘢痕疙瘩和增生性瘢痕（HS）这两种过度瘢痕形成类型的基因表达特征。
对聚焦于瘢痕疙瘩和HS的已发表微阵列数据进行文献检索。对微阵列数据进行重新分析以鉴定共同显著失调（CSD）基因。系统评估研究的实验和统计参数，以揭示对研究间共识结果的任何影响。使用基因本体（GO）类别和通路的过表达分析来探索与过度瘢痕形成发病机制功能相关的显著失调基因。
鉴定出7项关于瘢痕疙瘩的已发表微阵列研究和4项关于HS的研究。在瘢痕疙瘩中总共鉴定出64个CSD基因；在HS中鉴定出9个上调的CSD基因。在至少1项瘢痕疙瘩研究和1项HS研究中重叠的48个持续失调基因被定义为过度瘢痕形成中的CSD基因。系统记录并评估了与研究方案和数据管理相关的变量差异。发现与骨骼发育、结合、细胞外基质-受体相互作用和黏附相关的激活GO类别和通路在过度瘢痕形成中具有重要意义，这意味着瘢痕疙瘩和HS形成具有共同的病理基础。值得注意的是，与癌症相关的GO类别和TGF-β信号通路在瘢痕疙瘩中显著富集。
作为过度瘢痕形成的基因特征和分子标志物，鉴定出的CSD基因可能与疾病发病机制特别相关，并可作为新的治疗靶点。
