Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan 710, Taiwan.
Departments of Pathology, Chi Mei Medical Center, Tainan 710, Taiwan.
Int J Mol Sci. 2018 Apr 19;19(4):1242. doi: 10.3390/ijms19041242.
Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Some of the urinary bladder urothelial carcinomas (UBUCs) develop local recurrence and may cause distal invasion. Galectin-1 de-regulation significantly affects cell transformation, cell proliferation, angiogenesis, and cell invasiveness. In continuation of our previous investigation on the role of galectin-1 in UBUC tumorigenesis, in this study, proteomics strategies were implemented in order to find more galectin-1-associated signaling pathways. The results of this study showed that galectin-1 knockdown could induce 15 down-regulated proteins and two up-regulated proteins in T24 cells. These de-regulated proteins might participate in lipid/amino acid/energy metabolism, cytoskeleton, cell proliferation, cell-cell interaction, cell apoptosis, metastasis, and protein degradation. The aforementioned dys-regulated proteins were confirmed by western immunoblotting. Proteomics results were further translated to prognostic markers by analyses of biopsy samples. Results of cohort studies demonstrated that over-expressions of glutamine synthetase, alcohol dehydrogenase (NADP⁺), fatty acid binding protein 4, and toll interacting protein in clinical specimens were all significantly associated with galectin-1 up-regulation. Univariate analyses showed that de-regulations of glutamine synthetase and fatty acid binding protein 4 in clinical samples were respectively linked to disease-specific survival and metastasis-free survival.
在各种异质类型的膀胱肿瘤中,尿路上皮癌是最常见的病变。一些膀胱尿路上皮癌(UBUC)会发生局部复发,并可能导致远处侵犯。半乳糖凝集素-1 的失调会显著影响细胞转化、细胞增殖、血管生成和细胞侵袭性。继我们之前对半乳糖凝集素-1 在 UBUC 肿瘤发生中的作用的研究之后,在本研究中,我们采用蛋白质组学策略来寻找更多与半乳糖凝集素-1 相关的信号通路。本研究的结果表明,galectin-1 敲低可诱导 T24 细胞中 15 个下调蛋白和 2 个上调蛋白。这些失调蛋白可能参与脂质/氨基酸/能量代谢、细胞骨架、细胞增殖、细胞-细胞相互作用、细胞凋亡、转移和蛋白质降解。通过 Western 免疫印迹验证了上述失调蛋白。蛋白质组学结果通过对活检样本的分析进一步转化为预后标志物。队列研究的结果表明,临床标本中谷氨酰胺合成酶、醇脱氢酶(NADP⁺)、脂肪酸结合蛋白 4 和 Toll 相互作用蛋白的过度表达均与半乳糖凝集素-1 的上调显著相关。单因素分析表明,临床样本中谷氨酰胺合成酶和脂肪酸结合蛋白 4 的失调分别与疾病特异性生存和无转移生存相关。