Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China; Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China.
Life Sci. 2021 Aug 1;278:119559. doi: 10.1016/j.lfs.2021.119559. Epub 2021 Apr 28.
Defective components resulting from DNA damage and repair mechanisms have been found to be underlying causes that affect the development and progression of different types of cancers, including squamous cell carcinoma (SCC). A more detailed classification of SCC is necessary for better application of DNA damage repair therapies.
We aimed to characterize the molecular profile of SCC by developing a classification system based on DNA damage repair gene expression profiles. An integrative analysis was performed using a metadata set of 1374 SCC human samples from the UCSC Genome Browser. We then analyzed genomic alterations and mutations, and genes-TF-microRNA regulatory relationships and conducted enrichment, survival, and immune infiltration analyses.
This study was conducted on a total of 1374 SCC patients and 402 DNA damage repair genes. Two subtypes were established using consensus clustering, with 1143 patients being of the Non DDR subtype and 231 patients being of the DDR subtype. MATH, mutation burden, and heterogeneity were significantly higher in Non-DDR subtype than in DDR subtype. Next, a total of 1081 differentially expressed genes and 21 microRNAs were identified between the two subtypes and a genes-TF-microRNA regulatory network was constructed. In addition, stromal score, immune score and ESTIMATE score were significantly lower for the Non-DDR subtype, while tumor purity was significantly lower for the DDR subtype. In addition, five pathways associated with DNA damage repair were all enriched in the DDR subtype.
Our study established two subtypes of SCC based on DNA damage repair, which may help to predict prognosis and determine the most suitable treatment for SCC patients.
已经发现，导致 DNA 损伤和修复机制缺陷的因素是影响不同类型癌症（包括鳞状细胞癌[SCC]）发展和进展的根本原因。为了更好地应用 DNA 损伤修复治疗，需要对 SCC 进行更详细的分类。
我们旨在通过开发一种基于 DNA 损伤修复基因表达谱的分类系统，来描绘 SCC 的分子特征。我们对来自 UCSC 基因组浏览器的 1374 个人类 SCC 样本的元数据集进行了综合分析。然后，我们分析了基因组改变和突变、基因-TF-微小 RNA 调控关系，并进行了富集、生存和免疫浸润分析。
这项研究共涉及 1374 名 SCC 患者和 402 个 DNA 损伤修复基因。使用共识聚类方法建立了两个亚型，其中 1143 名患者是非 DDR 亚型，231 名患者是 DDR 亚型。在非 DDR 亚型中，MATH、突变负担和异质性显著高于 DDR 亚型。接下来，在两个亚型之间共鉴定出 1081 个差异表达基因和 21 个 microRNA，并构建了一个基因-TF-microRNA 调控网络。此外，非 DDR 亚型的基质评分、免疫评分和 ESTIMATE 评分显著较低，而 DDR 亚型的肿瘤纯度显著较低。此外，与 DNA 损伤修复相关的 5 条通路在 DDR 亚型中均显著富集。
我们的研究基于 DNA 损伤修复建立了 SCC 的两个亚型，这可能有助于预测 SCC 患者的预后，并确定最适合的治疗方案。
