Abstract：
N-acetylgalactosaminyltransferases (GALNTs) are a polypeptide responsible for aberrant glycosylation in breast cancer (BC), but the mechanism is unclear. In this study, expression levels of GALNT6, GALNT14, and Gal-3 were assessed in BC, and their association with GDF-15, β-catenin, stemness (SOX2 and OCT4), and drug resistance marker (ABCC5) was evaluated. Gene expression of GALNT6, GALNT14, Gal-3, GDF-15, OCT4, SOX2, ABCC5, and β-catenin in tumor and adjacent non-tumor tissues (n = 30) was determined. The same was compared with GEO-microarray datasets. A significant increase in the expression of candidate genes was observed in BC tumor compared to adjacent non-tumor tissue; and in pre-therapeutic patients compared to post-therapeutic. GALNT6, GALNT14, Gal-3, and GDF-15 showed positive association with β-catenin, SOX2, OCT4, and ABCC5 and were significantly associated with poor Overall Survival. Our findings were also validated via in silico analysis. Our study suggests that GALNT6, GALNT14, and Gal-3 in association with GDF-15 promote stemness and intrinsic drug resistance in BC, possibly by β-catenin signaling pathway.
摘要：
N-乙酰半乳糖胺转移酶（GALNTs）是负责乳腺癌（BC）中异常糖基化的多肽，但机制尚不清楚。在这项研究中,在BC中评估GALNT6，GALNT14和Gal-3的表达水平，以及它们与GDF-15、β-连环蛋白、干性(SOX2和OCT4)，并对耐药标志物(ABCC5)进行评价。测定了肿瘤和邻近非肿瘤组织(n=30)中GALNT6、GALNT14、Gal-3、GDF-15、OCT4、SOX2、ABCC5和β-catenin的基因表达。与GEO微阵列数据集进行比较。与邻近的非肿瘤组织相比,在BC肿瘤中观察到候选基因的表达显著增加;与治疗后相比,在治疗前患者中观察到候选基因的表达显著增加。GALNT6，GALNT14，Gal-3和GDF-15与β-catenin呈正相关，SOX2、OCT4和ABCC5与低总生存率显著相关。我们的发现也通过计算机模拟分析得到了验证。我们的研究表明，GALNT6，GALNT14和Gal-3与GDF-15相关，可促进BC的干性和内在耐药性，可能通过β-catenin信号通路。
