Clinical observation of microsatellite instability and PTEN mutations in predicting the efficacy and prognosis of adjuvant chemotherapy for resectable gastric cancer
Objective To detect microsatellite instability(MSI)and phosphatase and tensin homolog(PTEN)gene mutations in gastric cancer tissue,and their relationship with the efficacy and prognosis of adjuvant chemotherapy in gastric cancer patients.Methods A total of 115 patients with stage Ⅱ/Ⅲ indirect R0 D2 gastrectomy at the 980 Hospital of the Joint Logistics Support Force of the People's Liberation Army from January 2021 to June 2022 were collected.The expression of PTEN protein and programmed death receptor ligand 1(PD-L1)protein was detected using immunohistochemistry,and changes in PTEN copy number were analyzed using second-generation sequencing(NGS).Multiple polymerase chain reaction(PCR)was used to detect MSI status.Kaplan-Meier method was used to plot survival curves,and log rank tests were performed on survival differences.Cox proportional hazards regression model analysis of factors affecting the prognosis of gastric cancer patients.Results There were a total of 23 PTEN mutations and 55 PTEN protein negative expressions.PTEN mutations are related to PTEN protein expression,PD-L1 expression,EBV infection,and MSI status,and the differences are statistically significant(P＜0.05).According to MSI status and PTEN mutations,patients were divided into MSS/PTENwild subgroup(n=83),MSI/PTENwild subgroup(n=9),MSI/PTENmutant subgroup(n=12),and MSS/PTENmutant subgroup(n=11).The median OS of the four groups were 16.50,18.20,7.36 and 4.50 months,respectively,with statistically significant differences(P＜0.001).Multivariate Cox risk proportional regression model analysis showed that PD-L1 expression and MSI/PTEN status were independent factors affecting OS in gastric cancer patients(P＜0.05).In the MSS/PTENmutant subgroup,PD-L1 negative patients had a poorer prognosis in OS compared to PD-L1 positive patients(P=0.035).In the MSI/PTENwild subgroup or MSS/PTENwild subgroup,PD-L1 expression was not associated with prognosis(P＞0.05).PD-L1 expression is an independent factor for OS in the MSS/PTENmutant subgroup(HR=0.612,95%CI:0.389-0.962,P=0.033).Conclusion The combination of molecular typing and PD-L1 expression can serve as a potential strategy to better predict the prognosis of gastric cancer patients.
Gastric cancerPhosphatase and tensin homolog(PTEN)Microsatellite instability(MSI)PrognosisEpstein-Barr virus
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