Jiang Haoli, Guo Wei, Yuan Shanyou, Song Lixia
Department of Orthopedics, The Third People's Hospital of Shenzhen Shenzhen, China.
Int J Clin Exp Pathol. 2019 Oct 1;12(10):3752-3760. eCollection 2019.
Osteosarcoma is the most malignant bone tumor in adolescents. Molecules that are significantly associated with prognosis of osteosarcoma remain to be elucidated. In this study, we aimed to explore the prognostic role of Matrilin-2 (MATN2) in osteosarcoma.
By in silico analysis, we used GSE42352, GSE33382, and GSE21257 to explore the differential expression in osteosarcoma patients with different tumor status. Tissue and serum levels of MATN2 in 56 osteosarcoma patients were verified by RT-PCR and ELISA kits, respectively. Small interfering RNA was used to interfere with the expression of MATN2 in U-2OS and MG-63. CCK-8 and transwell assay were used to detect cell proliferation and migration, respectively. Western blot was used to detect the expression of invasion-related proteins.
MATN2 was overexpressed both in osteosarcoma cells and tissues when compared to normal controls. Both tissue and serum level of MATN2 correlated with tumor Enneking stage and metastasis status in osteosarcoma patients according to GEO datasets and validation cohort. Further Kaplan-Meier analysis revealed that MATN2 was a novel prognostic marker in patients with osteosarcoma. Knockdown of MATN2 by siRNA significantly reduced the proliferation and invasion of osteosarcoma cells in vivo. Furthermore, inhibition of MATN2 in U-2OS and MG-63 cells dramatically reduced the expression of mmp2, vimentin and snail1.
Elevated MATN2 in tissues and serum significantly associated with both tumor malignancy and poor outcome, which indicates MATN2 could be a prognostic biomarker in patients with osteosarcoma.
骨肉瘤是青少年中最具侵袭性的骨肿瘤。与骨肉瘤预后显著相关的分子仍有待阐明。在本研究中,我们旨在探讨基质金属蛋白酶2(MATN2)在骨肉瘤中的预后作用。
通过生物信息学分析,我们使用GSE42352、GSE33382和GSE21257来探索不同肿瘤状态的骨肉瘤患者中的差异表达。分别通过RT-PCR和ELISA试剂盒验证了56例骨肉瘤患者组织和血清中MATN2的水平。使用小干扰RNA干扰U-2OS和MG-63中MATN2的表达。分别使用CCK-8和Transwell实验检测细胞增殖和迁移。蛋白质免疫印迹法检测侵袭相关蛋白的表达。
与正常对照相比,MATN2在骨肉瘤细胞和组织中均过表达。根据GEO数据集和验证队列,骨肉瘤患者的MATN2组织和血清水平均与肿瘤Enneking分期和转移状态相关。进一步的Kaplan-Meier分析表明,MATN2是骨肉瘤患者的一种新的预后标志物。通过siRNA敲低MATN2可显著降低骨肉瘤细胞在体内的增殖和侵袭。此外,抑制U-2OS和MG-63细胞中的MATN2可显著降低mmp2、波形蛋白和snail1的表达。
组织和血清中MATN2升高与肿瘤恶性程度和不良预后均显著相关,这表明MATN2可能是骨肉瘤患者的预后生物标志物。