Wu Shu-Hua, Xu Xiao-Yang, Sun Chen-Bo, Wen Fei-Fei, He Shuang, Gao Xiang-Qian, Liu Yuan-Hang, Liu Liu
Department of Pathology, Binzhou Medical University Hospital Binzhou, Shandong Province, China.
Int J Clin Exp Pathol. 2019 Aug 1;12(8):2909-2919. eCollection 2019.
PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) belongs to the phosphokinase family, that has been reported to play an important role in several cancers. However, the expression of PHLPP2 and its correlation with clinicopathologic characteristics in colorectal cancer (CRC) have yet to be determined. The aim of this study is to investigate the expression of PHLPP2 and explore its role in CRC. The expression of PHLPP2, PTEN, PI3KCA, and PI3KCB in 130 cases of CRC and normal tissues was assessed by immunohistochemistry. In addition, the expression of PHLPP2, PTEN, PI3KCA, and PI3KCB in 32 pairs of CRC tissues and their corresponding normal tissues was determined by RT-PCR and western blotting, respectively. PHLPP2 expression in CRC was significantly lower than that of normal tissues. However, PHLPP2 mRNA shows no significant difference between CRC and normal tissue. PTEN expression in left colorectal cancer (LCC) was absent, while PI3KCA and PI3KCB in right colorectal cancer (RCC) were significantly higher than those in LCC. PHLPP2 was negatively correlated with p-Akt1 in CRC. The expression of p-Akt1 in PHLPP2 (+)/PTEN (+) in CRC tissues was significantly lower than that in other groups. PHLPP2 expression was correlated with differentiation, invasion, and lymph node metastasis. Kaplan-Meier analysis and multivariate analysis reveal that PHLPP2 is closely related to prognosis; more importantly, it is an independent prognostic factor for CRC. In conclusion, PHLPP2 may play a major role in the development, metastasis, and prognosis of CRC.
PH结构域富含亮氨酸重复蛋白磷酸酶2(PHLPP2)属于磷酸激酶家族,据报道其在多种癌症中发挥重要作用。然而,PHLPP2在结直肠癌(CRC)中的表达及其与临床病理特征的相关性尚未确定。本研究旨在探讨PHLPP2的表达并探究其在CRC中的作用。采用免疫组织化学法评估130例CRC组织和正常组织中PHLPP2、PTEN、PI3KCA和PI3KCB的表达。此外,分别采用RT-PCR和蛋白质印迹法检测32对CRC组织及其相应正常组织中PHLPP2、PTEN、PI3KCA和PI3KCB的表达。CRC中PHLPP2的表达明显低于正常组织。然而,CRC与正常组织之间PHLPP2 mRNA无显著差异。左半结肠癌(LCC)中PTEN无表达,而右半结肠癌(RCC)中PI3KCA和PI3KCB明显高于LCC。CRC中PHLPP2与p-Akt1呈负相关。CRC组织中PHLPP2(+)/PTEN(+)组的p-Akt1表达明显低于其他组。PHLPP2表达与分化、侵袭及淋巴结转移相关。Kaplan-Meier分析和多因素分析显示,PHLPP2与预后密切相关;更重要的是,它是CRC的独立预后因素。总之,PHLPP2可能在CRC的发生、转移及预后中起主要作用。