Correlation between CDK4 and TP53 gene mutations and prognosis in patients with gastric stromal tumors before adjuvant therapy
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摘要: [目的]比较高复发转移风险与非高复发转移风险胃间质瘤(GST)患者TP53和CDK4基因的表达水平差异,TP53和CDK4基因的表达水平对高复发转移风险GST患者术后伊马替尼辅助治疗的预后影响。[方法]前瞻性纳入收治行根治切除术的143例原发性GST患者,根据《中国胃肠间质瘤诊断治疗专家共识》将原发性GST患者分为高风险组(62例)和非高风险组(81例)。术后取瘤组织做免疫组化检测,比较2组间p53(TP53基因编码的蛋白)和CDK4表达情况。高风险组给予术后伊马替尼辅助治疗,再根据免疫组化结果,将62例高风险组患者分为p53高表达组、p53低表达组和CDK4高表达组、CDK4低表达组进行亚组分析。分别比较高表达组和低表达组间5年无事件生存率。[结果]高风险组和低风险组的年龄和性别比例差异无统计学意义。而高风险组的原发肿瘤大小较非高风险组大,分别为(11.53±2.81)cm、(8.25±1.52)cm(P<0.001),且肿瘤的核分裂数较非高风险组多,分别为12.24±2.32、7.52±2.21(P<0.001)。免疫组化结果提示,高风险组p53蛋白表达水平较非高风险组高,而CDK4蛋白表达水平较非高风险组低。在高风险组中,p53高表达组的5年无事件生存率较低表达组低,分别为45.6%、78.4%(P=0.044);然而,CDK4高表达组的5年无事件生存率较低表达组高,分别为74.2%、48.4%(P=0.029)。[结论]高复发、高转移风险的GST患者TP53基因表达水平较高;CDK4表达水平较低。更高的TP53基因表达和更低的CDK4表达水平提示着高复发、转移风险的GST术后伊马替尼辅助治疗有更好的预后。Abstract: [Objective]Comparing the expression levels of TP53 and CDK4 genes in patients with high risk of recurrence and metastasis and those with non-high risk of recurrence and metastasis, and the effect of TP53 and CDK4 gene expression levels on the prognosis of postoperative imatinib adjuvant therapy in patients with high risk of recurrence and metastasis.[Methods]A prospective enrollment of 143 patients with primary GST who underwent radical resection in our hospital was divided into high-risk groups(62 patients)and non-surgical patients according to the consensus of Chinese gastrointestinal stromal tumor diagnosis and treatment experts.High risk group(81 cases).The tumor tissues were taken for immunohistochemistry,and the expression of p53(protein encoded by TP53 gene)and CDK4 were compared between the two groups.High-risk group was given adjuvant treatment with imatinib.According to the results of immunohistochemistry,62 high-risk patients were divided into p53 high expression group,p53 low expression group and CDK4 high expression group,and CDK4 low expression group.Group analysis.Five-year event-free survival rates were compared between the high-expression and low-expression groups,respectively. [Results]There were no significant differences in age(58.22 ± 5.21,56.74 ± 6.21)and sex ratio(37/25,51/30)between the high-risk and low-risk groups included in the study(P>0.05).The size of the primary tumor in the high-risk group was larger than that in the non-high-risk group,which was(11.53±2.81)cm,(8.25±1.52)cm(P<0.001),and the number of mitotic divisions in the tumor was higher than that in the non-high-risk group,which was 12.24±2.32,7.52±2.21,P<0.001.The results of immunohistochemistry indicated that the expression level of p53 protein in high-risk group was higher than that in non-high-risk group,while the expression level of CDK4 protein was lower than that in non-high-risk group.In the high-risk group,the five-year event-free survival rate was lower in the low-expression group of the p53-high expression group,45.6%,78.4%,P=0.044.However,CDK4 was highly expressed.The group's five-year event-free survival rate was lower in the expression group,which was 74.2%,48.4%,P=0.029. [Conclusion]Gastric stromal tumors with high recurrence and metastasis risk have higher TP53 gene expression level and lower CDK4 expression level.Higher TP53 gene expression and lower CDK4 expression levels suggest a better prognosis for the prognosis of patients with high recurrence and metastatic gastric stromal tumors after imatinib adjuvant therapy.
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Key words:
- gastric stromal tumor /
- adjuvant therapy /
- imatinib /
- TP53 gene /
- CDK4 gene /
- prognosis
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