胰腺癌组织中PSAT1表达及其介导的细胞增殖侵袭作用机制研究

Expression of PSAT1 in pancreatic cancer tissues and the mechanism underlying PSAT1-mediated cell proliferation and invasion

目的:探讨胰腺癌磷酸丝氨酸转氨酶1(phosphoserine aminotransferase 1,PSAT1)表达及其介导的增殖、侵袭作用机制。方法:采用免疫组织化学染色检测2013年7月至2017年7月98例胰腺癌组织和癌旁组织PSAT1表达,分析PSAT1表达与胰腺癌临床资料、总体生存率、无病生存率的关系。分别向胰腺癌细胞BxPC-3、SW1990转染PSAT1-siRNA,研究敲低PSAT1表达对细胞增殖、迁移和侵袭的影响,Western blot检测敲低PSAT1对胰腺癌细胞PI3K/Akt/mTOR通路相关蛋白表达的影响。结果:PSAT1在胰腺癌组织中阳性表达率为69.4%(68/98),明显高于癌旁组织的阳性表达率5.0%(5/98),两者比较差异具有统计学意义(χ2=86.638,P<0.001)。PSAT1表达阳性率与淋巴结转移、TNM分期有关(P<0.05);PSAT1高表达的胰腺癌患者总生存期和无病生存期明显低于PSAT1低表达患者(P<0.05)。Cox多因素结果显示,PSAT1表达是影响胰腺癌总体生存率和无病生存率的危险因素(均P<0.05)。在胰腺癌BxPC-3和SW1990细胞中,与NC-siRNA组比较,PSAT1-siRNA组细胞增殖能力、迁移能力和细胞侵袭能力明显减弱,差异具有统计学意义(P<0.05)。同时PSAT1-siRNA组p-Akt、p-mTOR蛋白表达明显低于NC-siRNA组,差异具有统计学意义(P<0.05)。结论:PSAT1在胰腺癌组织和细胞中呈高表达,PSAT1可能通过调节PI3K/Akt/mTOR通路参与胰腺癌细胞的增殖和侵袭。

Objectives: To investigate the expression of phosphoserine aminotransferase 1(PSAT1) in pancreatic cancer tissues, and its potential role in pancreatic cancer. Methods: The expression of PSAT1 in 98 human pancreatic cancer tissues, which were collected from the People’s Hospital of Guizhou, between July 2013 to July 2017, and the corresponding adjacent normal tissues was analyzed by immunohistochemical staining. Additionally, the relationship between the expression of PSAT1 and the clinicopathological parameters, overall survival(OS), and disease-free survival(DFS) of patients with pancreatic cancer was evaluated. The human pancreatic cancer cell lines, BxPC-3 and SW1990, were transfected with PSAT1-siRNA, to investigate the effect of PSAT1 knockdown on cell proliferation, migration, and invasion. Additionally, we performed Western blot to assess the expression of PI3K/Akt/mTOR-related proteins in PSAT1-knockdown cells. Results: The percentages of PSAT1-positive cells in pancreatic cancer and adjacent non-tumor tissues were69.4%(68/98) and 5.0%(5/98), respectively, indicating a significantly higher expression of PSAT1 in pancreatic cancer tissues compared to adjacent non-tumor tissues(P<0.05). The increased expression of PSAT1 in pancreatic cancer tissues correlated with lymph node metastasis and TNM stage. Kaplan-Meier analysis suggested that a high expression of PSAT1 correlated with a poor OS and DFS compared to a low expression of PSAT1(P<0.05). Cox regression analysis showed that the expression of PSAT1 is an independent prognostic marker for OS and DFS in pancreatic cancer patients(P<0.05, all). Transient transfection of BxPC-3 and SW1990 cells with PSAT1-siRNA markedly reduced the cell proliferation, migration, and invasion abilities of these cells compared to transfection with NC-siRNA(P<0.05). Knockdown of PSAT1 in pancreatic cancer cells also inhibited the expression of p-Akt and p-mTOR(P<0.05). Conclusions: The expression of PSAT1 increases in human pancreatic cancer tissues and cell lines. Additionally, PSAT1 regulates cell proliferation and invasion through the PI3K/Akt/mTOR pathway.