| Objective:To detect the protein expression and gene mutation of PIK3 CA,Phosphatase and tensin homolog(PTEN)and The programmed death-1(PD-L1)in the Umbrella of normal fallopian(UNF),Ovarian Serous borderline tumor(OSBT),Low-grade serous ovarian cancer(LGSOC)and High-grade serous ovarian cancer(HGSOC)and explore the role of the three molecules in the occurrence and development of HGSOC and their relationship with clinicopathological features and prognosis in this study.Methods:1.Ninety-five cases(including 10 OSBT cases,20 LGSOC cases and 65 HGSOC cases)were collected from the Department of Pathology of Hospital of Zunyi Medical University from January 2013 to December 2019,and all of them were clearly diagnosed by two pathologists with titles above deputy chief physicians,and 10 UNF cases were selected for reference.2.Immunohistochemistry(IHC)Envision method was detected the protein expression of PIK3 CA,PTEN and PD-L1 and Next Generation sequencing(NGS)was detected the mutations of pik3 ca and pten genes in HGSOC.3.According to the Experimental data and results,SPSS 22.0 software was used for statistical analysis of the data to explore the expression of PIK3 CA,PTEN and PD-L1 proteins and the mutations of pik3 ca and pten gene and their clinical and prognostic significance in HGSOC.Results:1.Expressions of PIK3 CA,PTEN and PD-L1 proteins in UNF,OSBT,LGSOC and HGSOC and their clinical significance:The positive expression rate of PIK3 CA was found at 0%(0/10)for UNF,10.0%(1/10)for OSBT,15.0%(3/20)for LGSOC,and 32.3%(22/65)for HGSOC,The MOD values were 0.01±0.00,0.04±0.01,0.07±0.02,and 0.12±0.03,respectively;The positive expression rate of PTEN was 70.0%(7/10)for UNF,80.0%(8/10)for OSBT,40.0%(8/10)for LGSOC,and 23.1%(15/65)for HGSOC,The MOD values were0.16±0.02,0.17±0.02,0.07±0.02,and 0.04±0.01,respectively;The positive expression rate of PD-L1 was 0%(0/10)at UNF,10.0%(1/10)at OSBT,30.0%(6/20)at LGSOC,and 61.5%(40/65)at HGSOC,The MOD values were 0.01±0.00,0.05±0.01,0.08±0.01,and 0.15±0.02,respectively.We found that PIK3 CA and PD-L1 were positively increased(P <0.05),while PTEN was contrary to PIK3 CA and PD-L1 with higher histological grade(P <0.05).Positive expression of PIK3 CA,PTEN and PD-L1 protein were closely related to FIGO stage and lymph node metastasis status in HGSOC patients(P <0.05),namely higher FIGO stage,higher PIK3 CA and PD-L1 expression,while lower positive PTEN expression,more likely metastasis;otherwise,lower FIGO stage,lower PIK3 CA and PD-L1 expression,higher PTEN positive expression and less metastasis in lymph nodes.However,none of the above three molecules were related with clinical characteristics including chemotherapy resistance,peritoneal metastasis and serum CA125 content(P> 0.05).2.Mutations of pik3 ca and pten genes in UNF,OSBT,LGSOC and HGSOC and their clinical significance:Pik3ca and pten gene detection in each experimental group showed that pik3 ca and pten mutations only existed in the group of HGSOC,both of which were systematic mutations,with mutation rates of 13.3% and 6.7%,respectively.Among them,the pik3 ca gene is mainly missense or frameshift mutations,while the pten group is missense mutations,The mutation of the former was in exon 9 and 20,while the mutation of the latter was in exon 2 and 6,respectively.However,the mutation rate of the pik3 ca and pten genes in the UNF,OSBT,and LGSOC groups was 0.The comparison of the difference between the last two mutation rates in HGSOC was not statistically significant(P> 0.05).Statistical analysis was conducted by combining clinicopathological characteristics of patients and mutation results of HGSOC group,we found that mutations in the pik3 ca gene were associated with FIGO stage(P <0.05),not related with the patient’s lymph node metastasis or serum CA125 levels(P> 0.05).Mutations in the pten gene were not associated with the patient’s FIGO stage,lymph node metastasis,and serum CA125 levels(P> 0.05).Correlation analysis of PIK3 CA,PTEN,and PD-L1 proteins in HGSOC and mutation consistency test with pik3 ca and pten genes:The Chi-square linkage table and the number of column associations showed that there was a strong correlation between PIK3 CA and PD-L1 protein(r=0.652)(P<0.05),indicating that PIK3 CA protein increased with the increase of PD-L1 protein,and vice versa;There was a strong correlation between PD-L1 protein and PTEN protein(r=0.626)(P <0.05),indicating that PD-L1 protein decreased with the increase of PTEN protein expression,and vice versa.Finally,there was a weak correlation between PIK3 CA and PTEN protein expression(r=0.300)(P <0.05).Kappa consistency test results: In the HGSOC group,NGS and IHC were poor(κ=0.022;κ=0.020)(P > 0.05),indicating that the test results of NGS and IHC were inconsistent.4.Effects of the PIK3 CA,PTEN,PD-L1 protein expression and the mutations of pik3 ca and pten genes on survival prognosis in HGSOC patients:The Kaplan-Meier survival analysis combining our follow-up and experimental data found that the overall survival rate of HGSOC patients was 35.4%(23 / 65).Among of which,patients with PIK3CA3 and PD-L1 positive proteins had shorter survival time(P <0.05)and worse prognosis than negative patients,and compared to PIK3CA3 and PD-L1 proteins,PTEN protein-positive patients survived longer(P <0.05)and had better prognosis.In addition,the differential effect of pik3 ca and pten mutations on the total survival time of HGSOC patients were statistically significant(P > 0.05).Conclusion:1.The protein expression of PIK3 CA and PD-L1 in HGSOC suggests that they participate in and promote the occurrence and development of HGSOC,while PTEN molecule can inhibit the progression of HGSOC,all of which can provide help for the diagnosis and treatment of HGSOC.2.Correlation analysis of PIK3 CA,PD-L1 and PTEN protein expression in HGSOC showed that PIK3 CA and PD-L1 had a synergistic effect in promoting the development of ovarian cancer;PD-L1 and PTEN may have antagonistic effects on the evolution of HGSOC.3.Through the analysis of the relationship between the expression of PIK3 CA,PTEN and PD-L1 and the clinicopathological features and survival prognosis of patients with HGSOC,it is suggested that PIK3 CA,PTEN and PD-L1 can all be used as biomarkers and therapeutic targets for HGSOC,and provide important theoretical and clinical basis for the clinical treatment of serous ovarian cancer. |
