Bispo Iasmin Moreira Costa, Granger Henry Paul, Almeida Palloma Porto, Nishiyama Patricia Belini, de Freitas Leandro Martins
Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil.
Division of Experimental and Translational Research, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, Brazil.
World J Clin Oncol. 2022 Oct 24;13(10):762-778. doi: 10.5306/wjco.v13.i10.762.
Gastrointestinal (GI) cancers are a set of diverse diseases affecting many parts/ organs. The five most frequent GI cancer types are esophageal, gastric cancer (GC), liver cancer, pancreatic cancer, and colorectal cancer (CRC); together, they give rise to 5 million new cases and cause the death of 3.5 million people annually. We provide information about molecular changes crucial to tumorigenesis and the behavior and prognosis. During the formation of cancer cells, the genomic changes are microsatellite instability with multiple chromosomal arrangements in GC and CRC. The genomically stable subtype is observed in GC and pancreatic cancer. Besides these genomic subtypes, CRC has epigenetic modification (hypermethylation) associated with a poor prognosis. The pathway information highlights the functions shared by GI cancers such as apoptosis; focal adhesion; and the p21-activated kinase, phosphoinositide 3-kinase/Akt, transforming growth factor beta, and Toll-like receptor signaling pathways. These pathways show survival, cell proliferation, and cell motility. In addition, the immune response and inflammation are also essential elements in the shared functions. We also retrieved information on protein-protein interaction from the STRING database, and found that proteins Akt1, catenin beta 1 (CTNNB1), E1A binding protein P300, tumor protein p53 (TP53), and TP53 binding protein 1 (TP53BP1) are central nodes in the network. The protein expression of these genes is associated with overall survival in some GI cancers. The low TP53BP1 expression in CRC, high EP300 expression in esophageal cancer, and increased expression of Akt1/TP53 or low CTNNB1 expression in GC are associated with a poor prognosis. The Kaplan Meier plotter database also confirmed the association between expression of the five central genes and GC survival rates. In conclusion, GI cancers are very diverse at the molecular level. However, the shared mutations and protein pathways might be used to understand better and reveal diagnostic/prognostic or drug targets.
胃肠道（GI）癌症是一组影响多个部位/器官的多种疾病。五种最常见的GI癌症类型是食管癌、胃癌（GC）、肝癌、胰腺癌和结直肠癌（CRC）；它们每年共导致500万新发病例，并造成350万人死亡。我们提供了对肿瘤发生、行为和预后至关重要的分子变化信息。在癌细胞形成过程中，基因组变化在GC和CRC中表现为微卫星不稳定性以及多种染色体排列。在GC和胰腺癌中观察到基因组稳定亚型。除了这些基因组亚型外，CRC还存在与预后不良相关的表观遗传修饰（高甲基化）。通路信息突出了GI癌症共有的功能，如细胞凋亡、粘着斑以及p21激活激酶、磷酸肌醇3激酶/蛋白激酶B（PI3K/Akt）、转化生长因子β和Toll样受体信号通路。这些通路表现出生存、细胞增殖和细胞运动功能。此外，免疫反应和炎症也是这些共有功能中的重要因素。我们还从STRING数据库中检索了蛋白质-蛋白质相互作用信息，发现蛋白激酶B1（Akt1）、β-连环蛋白1（CTNNB1）、E1A结合蛋白P300、肿瘤蛋白p53（TP53）和TP53结合蛋白1（TP53BP1）是该网络中的中心节点。这些基因的蛋白表达与某些GI癌症的总生存期相关。CRC中TP53BP1低表达、食管癌中EP300高表达以及GC中Akt1/TP53表达增加或CTNNB1低表达与预后不良相关。Kaplan Meier绘图仪数据库也证实了这五个中心基因的表达与GC生存率之间的关联。总之，GI癌症在分子水平上非常多样化。然而，共享的突变和蛋白质通路可能有助于更好地理解和揭示诊断/预后或药物靶点。
