Correlation Of PHLPP2,PTEN And P-Akt1 Expression And Its Significance In Colorectal Cancer

ObjectiveDetect the expression of PHLPP2,PTEN,PI3KCA,PI3KCB,p-Akt1 and its downstream molecules,such as VEGF,Bcl-2 and Cyclin D1 in colorectal cancer(CRC),and explore their correlation and clinical significance.Materials and Methods256 paraffin specimens of CRC and corresponding normal tissues were collected from the Department of Pathology,Binzhou Medical University Hospital from January 2011 to December 2012.None of the selected cases received any radiotherapy or chemotherapy before operation,and all patients received FOXOL chemotherapy after operation.Follow-up calls or outpatient visits were conducted annually until December 2017 or death.32 fresh specimens of CRC from the Department of Pathology,Binzhou Medical University Hospital from January 2016 to December 2017 were collected.The corresponding normal tissues were taken as control.Some of the tissues were immediately frozen in liquid nitrogen and some were fixed in 10%neutral formalin.The expressions of PHLPP2,PTEN,PI3KCA,PI3KCB,p-Akt1,Bcl-2,Cyclin-D1 and VEGF in CRC and normal tissues were detected by IHC.The expressions of PHLPP2,PTEN,PI3KCA,PI3KCB,Akt1,Bcl-2,Cyclin-D1 and VEGF in 32 CRC and normal tissues were detected by Western Blot and RT-PCR.Results1.The positive rates of PHLPP2 and PTEN in CRC were lower than those in normal tissues.The positive rates of PI3KCA,PI3KCB,p-Akt1,VEGF,Bcl-2 and Cyclin D 1 in CRC were significantly higher than those in normal tissues.The mRNA of PTEN,PI3KCA,PI3KCB,VEGF,Bcl-2 and Cyclin-D1 in CRC and normal were significantly different,while the mRNA of PHLPP2 in CRC and normal were not significantly different.2.PHLPP2 was negatively correlated with p-Akt1,VEGF,Bcl-2 and Cyclin D1 in CRC,while there was no correlation between PHLPP2 and PTEN expression in CRC.The expression of p-Akt1 in PHLPP2(-)/PTEN(-)group was significantly higher than that in the other three groups;the expression of p-Akt1 in PHLPP2(+)/PTEN(+)group was significantly lower than that in other three groups.3.The expression of PTEN in left colon cancer was significantly lower than that in right colon cancer.On the contrary,the expression of PI3KCA and PI3KCB in right colon cancer was significantly higher.There was no difference in the expression of PHLPP2 between left and right colon cancer,but the prognosis of right colon cancer patients with positive expression of PHLPP2 was significantly better than that of negative expression.4.The expression of PHLPP2 was correlated with the degree of differentiation,depth of invasion and lymph node metastasis;the expression of PTEN was correlated with depth of invasion and lymph node metastasis;the expression of PI3KCA and PI3KCB was positively correlated with lymph node metastasis.Kaplan-Meier analysis showed that PHLPP2,PI3KCA and PI3KCB were closely related to the prognosis of patients with CRC,and patients with high expression of PHLPP and PTEN had a higher 5-year survival rate.Cox regression model showed that PHLPP2,PTEN,tumor location,invasion and lymph node metastasis were independent risk factors for prognosis of CRC.Conclusion1.The expression of PHLPP2 is low in colorectal cancer.And the loss of PHLPP2 expression in colorectal cancer occurs at post-transcriptional level,not at transcriptional level.2.In colorectal cancer,PHLPP2 and PTEN inhibit p-Akt activity from PI3K/PI3P and Akt/p-Akt levels respectively,and then inhibit tumor proliferation,angiogenesis and apoptosis.3.The poor prognosis of right colon cancer is related not only to the activation of oncogenes such as PI3KCA and PI3KCB,but also to the inactivation of PHLPP2.4.The inactivation of the tumor suppressor gene PHLPP2 is closely related to the prognosis of patients with colorectal cancer,and is one of independent risk factor for the prognosis of colorectal cancer.