磷酸甘油酸脱氢酶（PHGDH）是一种独立的预后标志物，在人类胰腺癌中促进细胞增殖、迁移和侵袭。

PHGDH is an independent prognosis marker and contributes cell proliferation, migration and invasion in human pancreatic cancer.

作者信息

Song Zhiwang, Feng Chan, Lu Yonglin, Lin Yun, Dong Chunyan

机构信息

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.

出版信息

Gene. 2018 Feb 5;642:43-50. doi: 10.1016/j.gene.2017.11.014. Epub 2017 Nov 8.

DOI:10.1016/j.gene.2017.11.014

PMID:29128633

Abstract

PURPOSE

To investigate the expression, clinical significance, biological function, and the potential mechanism of PHGDH in pancreatic cancer.

METHODS

The expression of PHGDH in human pancreatic cancer tissues and corresponding adjacent normal tissues were analyzed through immunohistochemistry staining. Simultaneously, the association between the PHGDH expression and the clinicopathological parameters and OS and DFS was evaluated. Human pancreatic cancer cell line BxPC-3 and SW1990 were selected to investigate the effect of PHGDH knockdown on cell proliferation, migration, and invasion. In addition, we performed western blot to assess the expression of cyclin B1, and cyclin D1, MMP-2, and MMP-9 protein.

RESULTS

Our results suggested that the expression of PHGDH is increased in pancreatic cancer compared with adjacent normal tissues and the increased expression of PHGDH is associated with tumor size, lymph node metastasis, and TNM state of pancreatic cancer patients. Moreover, the expression of PHGDH is an independent prognostic indicator for pancreatic cancer patients. In addition, we found that knockdown of PHGDH in pancreatic cancer cells inhibits the cell proliferation, migration, and invasion abilities by down-regulating the expression of cyclin B1, and cyclin D1, MMP-2, and MMP-9.

CONCLUSIONS

Our data indicated that the expression of PHGDH is increased in pancreatic cancer and is an independent molecular prognostic factor for pancreatic cancer patients. In addition, PHGDH controls cell proliferation, migration and invasion abilities. Therefore, PHGDH could serve as an important prognostic indicator and therapeutic target for pancreatic cancer.

摘要

目的

探讨磷酸甘油酸脱氢酶（PHGDH）在胰腺癌中的表达、临床意义、生物学功能及潜在机制。

方法

通过免疫组织化学染色分析PHGDH在人胰腺癌组织及相应癌旁正常组织中的表达。同时，评估PHGDH表达与临床病理参数、总生存期（OS）和无病生存期（DFS）之间的关联。选取人胰腺癌细胞系BxPC-3和SW1990，研究敲低PHGDH对细胞增殖、迁移和侵袭的影响。此外，进行蛋白质印迹法评估细胞周期蛋白B1、细胞周期蛋白D1、基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）蛋白的表达。

结果

我们的结果表明，与癌旁正常组织相比，胰腺癌中PHGDH的表达增加，且PHGDH表达的增加与胰腺癌患者的肿瘤大小（肿块大小）、淋巴结转移及TNM分期有关。此外，PHGDH的表达是胰腺癌患者的独立预后指标。另外，我们发现敲低胰腺癌细胞中的PHGDH可通过下调细胞周期蛋白B1、细胞周期蛋白D1、MMP-2和MMP-9的表达来抑制细胞的增殖、迁移和侵袭能力。