Proteome Atlas of Human Chromosome 8 and Its Multiple 8p Deficiencies in Tumorigenesis of the Stomach, Colon, and Liver

Chromosome 8, a medium-length euchromatic unit in humans
that has an extraordinarily high mutation rate, can be detected not
only in evolution but also in multiple mutant diseases, such as tumorigenesis,
and further invasion/metastasis. The Chromosome-Centric Human Proteome
Project of China systematically profiles the proteomes of three digestive
organs (i.e., stomach, colon, and liver) and their corresponding carcinoma
tissues/cell lines according to a chromosome organizational roadmap.
By rigorous standards, we have identified 271 (38.7%), 330 (47.1%),
and 325 (46.4%) of 701 chromosome 8-coded proteins from stomach, colon,
and liver samples, respectively, in Swiss-Prot and observed a total
coverage rate of up to 58.9% by 413 identified proteins. Using large-scale
label-free proteome quantitation, we also found some 8p deficiencies,
such as the presence of 8p21–p23 in tumorigenesis of the above-described
digestive organs, which is in good agreement with previous reports.
To our best knowledge, this is the first study to have verified these
8p deficiencies at the proteome level, complementing genome and transcriptome
data.

人类8号染色体属于中等长度的常染色质单元，其突变率极高，不仅可在演化进程中被观测到，还与多种突变性疾病相关，例如肿瘤发生以及后续的侵袭与转移。中国以染色体为中心的人类蛋白质组计划（Chromosome-Centric Human Proteome Project）按照染色体组织路线图，系统解析了胃、结肠、肝脏这三种消化器官及其对应癌组织/细胞系的蛋白质组。基于严格的鉴定标准，我们在Swiss-Prot数据库中，分别从胃、结肠和肝脏样本中，鉴定出701个8号染色体编码蛋白中的271个（占比38.7%）、330个（47.1%）与325个（46.4%），总计鉴定得到413个蛋白，总覆盖度可达58.9%。通过大规模无标记蛋白质组定量分析，我们还检测到部分8号染色体短臂（8p）缺失现象，例如上述消化器官肿瘤发生过程中存在8p21–p23区域缺失，该结果与既往研究报道高度吻合。据我们所知，本研究是首次在蛋白质组层面验证此类8p缺失现象，可为基因组与转录组数据提供重要补充。