Berkel Caglar, Cacan Ercan
Molecular Biology and Genetics Department, Tokat Gaziosmanpasa University, 60250, Tokat, Turkey.
J Cell Commun Signal. 2021 Mar;15(1):57-70. doi: 10.1007/s12079-020-00582-3. Epub 2020 Sep 4.
Ovarian cancer is the most lethal gynecological malignancy and molecular mechanisms of its progression and metastasis are not completely understood. Some members of GAB (GRB2-associated binding) protein family have been reported to be involved in tumor cell proliferation and metastasis in various cancer types. In the present study, we analyzed the expression of GAB proteins (GAB1, GAB2 and GAB3) in ovarian cancer compared to normal ovarian tissue, in terms of tumor stage, tumor grade and histological type. Differential expression analyses performed in R programming environment using multiple transcriptome datasets (n = 1449) showed that GAB1 expression is decreased in ovarian cancer independently of tumor stage, grade and histotype. Unlike GAB1, expression of GAB2 and GAB3 are increased from early stage to late stage and from low grade to high grade in epithelial ovarian cancer. GAB2 and GAB3 also showed histotype-dependent expression. GAB3 was computed as a top gene whose expression most significantly changed between tumor cells from primary tumor, metastases and ascites. High expression of GAB2 and GAB3 was shown to be associated with shorter progression-free survival in ovarian cancer. This study shows that GAB2 and GAB3 can be important regulators of tumor progression and metastasis in ovarian cancer.
卵巢癌是最致命的妇科恶性肿瘤,其进展和转移的分子机制尚未完全明确。据报道,GAB(GRB2相关结合)蛋白家族的一些成员参与了多种癌症类型的肿瘤细胞增殖和转移。在本研究中,我们根据肿瘤分期、肿瘤分级和组织学类型,分析了GAB蛋白(GAB1、GAB2和GAB3)在卵巢癌与正常卵巢组织中的表达情况。使用多个转录组数据集(n = 1449)在R编程环境中进行的差异表达分析表明,卵巢癌中GAB1的表达降低,且与肿瘤分期、分级和组织类型无关。与GAB1不同,在上皮性卵巢癌中,GAB2和GAB3的表达从早期到晚期、从低级别到高级别均升高。GAB2和GAB3也表现出组织类型依赖性表达。GAB3被确定为一个顶级基因,其表达在原发性肿瘤、转移灶和腹水中的肿瘤细胞之间变化最为显著。GAB2和GAB3的高表达与卵巢癌患者较短的无进展生存期相关。本研究表明,GAB2和GAB3可能是卵巢癌肿瘤进展和转移的重要调节因子。