Zhang Qia, Kanyomse Quist, Luo Chenghao, Mo Qingfan, Zhao XunPing, Wang Long, Peng Weiyan, Ren Guosheng
Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Cancer Invest. 2023 Feb;41(2):119-132. doi: 10.1080/07357907.2022.2128367. Epub 2022 Nov 11.
A disintegrin-like and metalloprotease with therombospondin type1 motif 8 (ADAMTS8) plays an important role in many malignancies. However, the clinical and biological significance of in breast cancer remain unknown. In this study, the clinical data from 1066 breast cancer patients were analyzed by The Cancer Genome Atlas (TCGA) database, and were analyzed using the correlation between expression and the clinicopathological features and prognoses. The CCK-8 assay, clone formation assay, flow cytometry and Transwell assay were used to characterize the effects of on proliferation, migration and invasion of breast cancer cells. Gene set enrichment analysis (GSEA) and western blotting were used to identify the potential molecular mechanism on how exert its biological function. overexpression correlated longer overall survival (OS) and progression-free survival (PFS). was considered as an independent prognostic factor for OS. overexpression inhibited breast cancer cell proliferation, migration and invasion , and induced G2/M cell cycle arrest. was also involved in cell cycle regulation and was associated with the EGFR/Akt signaling pathway. knockdown showed the reverse effect. Together, the results showed that functioned as a tumor suppressor gene (TGS) and could be a prognostic biomarker for breast cancer.
含血小板反应蛋白基序的解聚素样金属蛋白酶8(ADAMTS8)在许多恶性肿瘤中起重要作用。然而,其在乳腺癌中的临床和生物学意义仍不清楚。在本研究中,通过癌症基因组图谱(TCGA)数据库分析了1066例乳腺癌患者的临床数据,并利用ADAMTS8表达与临床病理特征及预后之间的相关性进行分析。采用CCK-8检测、克隆形成检测、流式细胞术和Transwell检测来表征ADAMTS8对乳腺癌细胞增殖、迁移和侵袭的影响。基因集富集分析(GSEA)和蛋白质免疫印迹法用于确定ADAMTS8发挥其生物学功能的潜在分子机制。ADAMTS8过表达与更长的总生存期(OS)和无进展生存期(PFS)相关。ADAMTS8被认为是OS的独立预后因素。ADAMTS8过表达抑制乳腺癌细胞增殖、迁移和侵袭,并诱导G2/M期细胞周期阻滞。ADAMTS8还参与细胞周期调控,并与表皮生长因子受体/蛋白激酶B(EGFR/Akt)信号通路相关。ADAMTS8敲低显示出相反的效果。总之,结果表明ADAMTS8作为一种肿瘤抑制基因(TSG)发挥作用,并且可能是乳腺癌的一种预后生物标志物。