Expression of phosphatase and tensin homologue deleted on chromosome ten gene in prostate cancer tissues and construction of oncolytic adenovirus loaded with phosphatase and tensin homologue deleted on chromosome ten gene
Objective To construct oncolytic adenovirus carrying gene of phosphatase and tensin homolog deleted on chromosome ten(PTEN)and verified its expression level in prostate cancer and targe-ted anti-tumor effects.Methods Mined public databases and used the Galaxy online tool to process gene sequencing data of castration-resistant prostate cancer(CRPC)specimens from our center,and analyzed the differences in PTEN gene expression in prostate cancer tissues.Collected pathological samples and clin-ical information of 79 prostate cancer patients from March 2019 to August 2022 at the Affiliated Hospital of Xuzhou Medical University,and detected the expression of PTEN protein in prostate cancer tissues and ad-jacent tissues by using immunohistochemistry.Constructed the oncolytic adenovirus ZD55-PTEN by using homologous recombination,and used the cell counting kit-8(CCK-8)method,Hoechst-33258,and scratch assay to detect its targeted anti-tumor effects.Chi-square test and t-test were used for statistical analysis of qualitative and quantitative data,respectively;Mann-Whitney U test was used for data that does not meet normal distribution.Spearman's analysis was used to assess the relationship between PTEN expression lev-els and clinicopathological features.Results The expression level of PTEN in prostate cancer tissues was significantly lower than that in adjacent non-cancerous tissues,with a statistically significant difference(501 cases vs.52 cases,Z=-19.25,P＜0.05).The mRNA expression level of PTEN was negatively correlated with lymph node metastasis(n=425,rs=-0.98,P＜0.05)and Gleason score(n=497,rs=-1.25,P＜0.05).The loss of PTEN in the CRPC stage was significantly higher than in the hormone-sen-sitive prostate cancer(HSPC)stage(79 cases vs.125 cases,Z=-0.89,P＜0.05).The rate of PTEN protein loss in prostate cancer tissues was higher than that in adjacent non-cancerous tissues(45.6％vs.16.5％,t=10.98,P＜0.01),and preoperative serum PSA levels(n=79,r,=-0.47,P＜0.01)and postoperative Gleason score(n=79,rs=-0.31,P＜0.05)were negatively correlated with PTEN expres-sion.Prostate cancer patients with PTEN loss had significantly higher PSA levels at the time of diagnosis(36 vs.43 cases,t=12.22,P＜0.05)and postoperative Gleason scores(36 cases vs.43 cases,t=6.92,P＜0.05)compared to patients with intact PTEN protein.The oncolytic adenovirus ZD55-PTEN was successfully constructed,and the cell viability in the ZD55-PTEN group was lower than that in the control group[ZD55-EGFP group(49.67±4.19)％,ZD55-PTEN group(29.33±3.84)％,t=8.68,P＜0.05];the apoptosis rate was higher than that in the control group[PBS group:(12.86±5.23)％,ZD55-EGFP group(48.18±4.22)％,ZD55-PTEN group(68.93±5.88)％,t=5.90,P＜0.05];and the scratch healing rate was lower than that in the control group[PBS group(79.13±3.98)％,ZD55-EGFP group(61.02±4.73)％,ZD55-PTEN group(47.92±5.97)％,t=6.34,P＜0.05].Conclusion The PTEN gene is underexpressed in prostate cancer tissues and exhibits the function of inhibiting the prolifera-tion and migration of DU145 cells and inducing apoptosis.
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