Zhang Botao, Wang Yuanjing, Li Hongxia, Feng Lin, Li Wenbin, Cheng Shujun
Department of Neuro-oncology, Neurosurgery Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Cell Dev Biol. 2020 Jun 23;8:492. doi: 10.3389/fcell.2020.00492. eCollection 2020.
The processes of embryonic development that rely on epithelial-mesenchymal transition (EMT) for the implantation of trophoblast cells are co-opted by tumors, reflecting their inherent uncontrolled characteristics and leading to invasion and metastasis. Although tumorigenesis and embryogenesis have similar EMT characteristics, trophoblasts have been shown to exhibit "physiological metastasis" or be "pseudo-malignant," resulting in different outcomes. The gene co-expression network is the basis of embryonic development and tumorigenesis. We hypothesize that if the gene co-expression network in tumors is "off-track" from that in villi, it is more likely to develop into malignant tumors and have a worse prognosis, and we proposed the "off-track theory" for the first time. In this study, we examined gene co-expression networks in villi and multiple solid tumors. Through network functional enrichment analyses, we found that most tumors and villi exhibited a significantly enriched EMT, but the genes that performed this function were not identical. Then, we identified the "off-track genes" in the EMT-related gene interaction network using the "off-track theory," and through survival analysis, we discovered that the risk score of "off-track genes" was associated with poor survival of cancer patients. Our study indicated that villi development is a reliable and strictly regulated model that can illuminate the trajectory of human cancer development and that the gene co-expression networks in tumor development are "off-track" from those in villi. These "off-track genes" may have a substantial impact on tumor development and could reveal novel prognostic biomarkers.
依赖上皮-间质转化（EMT）实现滋养层细胞着床的胚胎发育过程被肿瘤所利用，这反映了肿瘤固有的失控特性，并导致侵袭和转移。尽管肿瘤发生和胚胎发生具有相似的EMT特征，但已表明滋养层细胞表现出“生理性转移”或“假恶性”，从而导致不同的结果。基因共表达网络是胚胎发育和肿瘤发生的基础。我们假设，如果肿瘤中的基因共表达网络与绒毛中的“偏离轨道”，则其更有可能发展为恶性肿瘤且预后更差，并且我们首次提出了“偏离轨道理论”。在本研究中，我们检测了绒毛和多种实体瘤中的基因共表达网络。通过网络功能富集分析，我们发现大多数肿瘤和绒毛均表现出显著富集的EMT，但执行此功能的基因并不相同。然后，我们使用“偏离轨道理论”在EMT相关基因相互作用网络中鉴定出“偏离轨道基因”，并通过生存分析发现，“偏离轨道基因”的风险评分与癌症患者的不良生存相关。我们的研究表明，绒毛发育是一个可靠且严格调控的模型，可阐明人类癌症发展的轨迹，并且肿瘤发展中的基因共表达网络与绒毛中的“偏离轨道”。这些“偏离轨道基因”可能对肿瘤发展产生重大影响，并可能揭示新的预后生物标志物。
