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糖基转移酶酶 GCNT3 在结肠癌和卵巢癌的预后和化疗耐药中的作用。

The role of glycosyltransferase enzyme GCNT3 in colon and ovarian cancer prognosis and chemoresistance.

机构信息

Molecular Oncology Group, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.

Biostatistics and Bioinformatics Unit, IMDEA-Food Institute, CEI UAM + CSIC, Madrid, Spain.

出版信息

Sci Rep. 2018 May 31;8(1):8485. doi: 10.1038/s41598-018-26468-4.

Abstract

Glycosyltransferase enzyme GCNT3, has been proposed as a biomarker for prognosis in colorectal cancer (CRC). Our study goes in depth into the molecular basis of GCNT3 role in tumorigenesis and drug resistance, and it explores its potential role as biomarker in epithelial ovarian cancer (EOC). High levels of GCNT3 are associated with increased sensibility to 5-fluoracil in metastatic cells. Accordingly, GCNT3 re-expression leads to the gain of anti-carcinogenic cellular properties by reducing cell growth, invasion and by changing metabolic capacities. Integrated transcriptomic and proteomic analyses reveal that GCNT3 is linked to cellular cycle, mitosis and proliferation, response to drugs and metabolism pathways. The vascular epithelial growth factor A (VEGFA) arises as an attractive partner of GCNT3 functions in cell invasion and resistance. Finally, GCNT3 expression was analyzed in a cohort of 56 EOC patients followed by a meta-analysis of more than one thousand patients. This study reveals that GCNT3 might constitute a prognostic factor also in EOC, since its overexpression is associated with better clinical outcome and response to initial therapy. GCNT3 emerges as an essential glycosylation-related molecule in CRC and EOC progression, with potential interest as a predictive biomarker of response to chemotherapy.

摘要

糖基转移酶 GCNT3 已被提议作为结直肠癌 (CRC) 预后的生物标志物。我们的研究深入探讨了 GCNT3 在肿瘤发生和耐药性中的分子基础,并探索了其作为上皮性卵巢癌 (EOC) 生物标志物的潜在作用。高水平的 GCNT3 与转移性细胞对 5-氟尿嘧啶的敏感性增加有关。相应地,GCNT3 的重新表达通过降低细胞生长、侵袭和改变代谢能力,导致获得抗癌的细胞特性。综合转录组和蛋白质组分析表明,GCNT3 与细胞周期、有丝分裂和增殖、对药物的反应以及代谢途径有关。血管内皮生长因子 A (VEGFA) 作为 GCNT3 参与细胞侵袭和耐药性的功能的有吸引力的伙伴出现。最后,分析了 56 名 EOC 患者的队列中的 GCNT3 表达,并对超过一千名患者进行了荟萃分析。这项研究表明,GCNT3 也可能构成 EOC 的预后因素,因为其过表达与更好的临床结果和对初始治疗的反应有关。GCNT3 作为 CRC 和 EOC 进展中与糖基化相关的重要分子出现,具有作为化疗反应预测生物标志物的潜在兴趣。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3a1/5981315/1d2828ebbb84/41598_2018_26468_Fig1_HTML.jpg

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