Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
Sci Rep. 2021 Nov 3;11(1):21549. doi: 10.1038/s41598-021-00943-x.
The extracellular matrix (ECM) has historically been explored through proteomic methods. Whether or not global transcriptomics can yield meaningful information on the human matrisome is unknown. Gene expression data from 17,382 samples across 52 tissues, were obtained from the Genotype-Tissue Expression (GTEx) project. Additional datasets were obtained from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus for comparisons. Gene expression levels generally matched proteome-derived matrisome expression patterns. Further, matrisome gene expression properly clustered tissue types, with some matrisome genes including SERPIN family members having tissue-restricted expression patterns. Deeper analyses revealed 382 gene transcripts varied by age and 315 varied by sex in at least one tissue, with expression correlating with digitally imaged histologic tissue features. A comparison of TCGA tumor, TCGA adjacent normal and GTEx normal tissues demonstrated robustness of the GTEx samples as a generalized matrix control, while also determining a common primary tumor matrisome. Additionally, GTEx tissues served as a useful non-diseased control in a separate study of idiopathic pulmonary fibrosis (IPF) matrix changes, while identifying 22 matrix genes upregulated in IPF. Altogether, these findings indicate that the transcriptome, in general, and GTEx in particular, has value in understanding the state of organ ECM.
细胞外基质 (ECM) 一直以来都是通过蛋白质组学方法进行探索的。全局转录组学是否能为人类基质组学提供有意义的信息尚不清楚。本研究从基因型-组织表达 (GTEx) 项目中获得了来自 52 种组织的 17382 个样本的基因表达数据。此外，还从癌症基因组图谱 (TCGA) 计划和基因表达综合数据库中获取了其他数据集进行比较。基因表达水平通常与蛋白质组学衍生的基质组表达模式相匹配。此外，基质组基因表达正确地对组织类型进行聚类，一些基质组基因，包括丝氨酸蛋白酶抑制剂家族成员，具有组织特异性的表达模式。更深入的分析显示，至少有 382 个基因转录本在一种组织中随年龄变化，315 个基因转录本在至少一种组织中随性别变化，其表达与数字化成像的组织学特征相关。TCGA 肿瘤、TCGA 相邻正常组织和 GTEx 正常组织的比较表明，GTEx 样本作为一般基质对照具有稳健性，同时也确定了常见的原发性肿瘤基质组。此外，GTEx 组织在一项特发性肺纤维化 (IPF) 基质变化的独立研究中作为有用的非疾病对照，同时确定了 22 个在 IPF 中上调的基质基因。总之，这些发现表明转录组，尤其是 GTEx，在了解器官 ECM 状态方面具有价值。
