摘要
目的血小板活化因子乙酰水解酶1B2(platelet activating factor acetyl hydrolase 1b2,PAFAH1B2)广泛参与肿瘤信号通路。本研究探讨PAFAH1B2表达状态与乳腺癌放疗及临床预后关系,以辨别潜在的放疗敏感性患者。方法采用癌症基因图谱(The Cancer Genome Atlas,TCGA)乳腺癌数据库中筛选的700例白种人患者PAFAH1B2基因mRNA二代测序数据和临床病理资料。根据样本中PAFAH1B2mRNA表达中值将患者分为PAFAH1B2高表达组(350例)和PAFAH1B2低表达组(350例)。Kaplan-Meier单因素和Cox回归多因素分析PAFAH1B2mRNA表达状态与乳腺癌放疗及临床预后关系;χ2检验分析PAFAH1B2表达状态与乳腺癌临床病理参数关联性。结果 PAFAH1B2表达状态与乳腺癌患者总生存率无关联,单因素和Cox回归多因素分析P值分别为0.221和0.063。但基于放疗和PAFAH1B2表达交互作用模型结果(P=0.001),说明PAFAH1B2不同表达水平下放疗疗效存在差异。PAFAH1B2低表达组,放疗与非放疗患者之间总生存率差异无统计学意义,P=0.272,多因素调整后差异仍无统计学意义,P=0.190,而PAFAH1B2高表达组,术后接受放疗较未放疗患者总生存率得到改善,HR=0.397,95%CI为0.217～0.727,P=0.002,多因素调整后差异仍有统计学意义,HR=0.299,95%CI为0.135～0.662,P=0.003。进一步研究发现,组织型为浸润性导管癌(infiltrating ductal carcinoma,IDC)或分子型为Luminal A型的PAFAH1B2高表达组,放疗患者较其他组别放疗患者总生存率改善;χ2检验分析显示,PAFAH1B2表达状态与肿瘤T分期(χ2=5.506,P=0.019)和组织分型(χ2=42.509,P=0.001)有关联,而与年龄、ER、PR、HER-2和术后组织边缘状况无关联。结论基因PAFAH1B2表达状态与乳腺癌患者放疗敏感性有关联,高表达PAFAH1B2的患者术后接受放疗总生存率提高,推测高表达PAFAH1B2的乳腺癌患者存在较好的放疗敏感性。
OBJECTIVE Platelet activating factor acetyl hydrolase 1 B2 is widely involved in tumor signaling pathways.The study investigated the relationship between PAFAH1 B2 expression status and breast cancer radiotherapy and clinical prognosis to identify potential radiosensitivity patients.METHODS The PAFAH1 B2 gene expression and clinical pathological information were downloaded from the cancer genome atlas breast cancer database.A total of 700 people were included in the statistical analysis.The patients were divided into PAFAH1 B2 high expression group(350 cases)and PAFAH1 B2 low expression group(350 cases)according to the median PAFAH1 B2 mRNA expression.Kaplan-Meier univariate and Cox regression multivariate factors were used to analyze the relationship between PAFAH1 B2 expression status and breast cancer radiotherapy and clinical prognosis.Chi-square test was used to analyze the correlation between the expression of PAFAH1 B2 and clinicopathological parameters of breast cancer.RESULTS There was no correlation between the state of PAFAH1 B2 expression and the overall survival rate of breast cancer patients,and the Pvalues of univariate analysis and Cox multivariate analysis were 0.221 and 0.063 respectively.However,based on the results of radiotherapy and PAFAH1 B2 expression interaction model(P=0.001),there were differences in the efficacy of radiotherapy at different expression levels of PAFAH1 B2.In the AFAH1 B2 low expression group,univariate analysisand multivariate analysis showed no significant difference in the overall survival rate between radiotherapy and no radiotherapy patients,and the Pvalues were 0.272 and 0.190,respectively.In the PAFAH1 B2 high expression group,the overall survival rate of patients receiving radiotherapy was significantly improved compared with those without radiotherapy.The HR was 0.397,95%CI was 0.217-0.727,P=0.002.The difference after multivariate adjustment was still statistically significant.HR was 0.299,95%CI was 0.135-0.662,P=0.003.Further investigation found that in tissue type of infiltrating ductal carcinoma(IDC)or molecular type of Luminal A PAFAH1 B2 high expression group,radiotherapy patients had better overall survival than other groups of patients.Chi-square analysis showed that the expression status of PAFAH1 B2 is associated with tumor T staging(χ2=5.506,P=0.019)and histological type(χ2=42.509,P=0.001),but was not related to age,ER,PR,HER-2 and postoperative tissue edge status.CONCLUSIONS The expression status of PAFAH1 B2 gene is correlated with the radiosensitivity of breast cancer patients.Patients with high expression of PAFAH1 B2 have a significant increase in overall survival after radiotherapy.We speculate that breast cancer patients with high expression of PAFAH1 B2 have better radiosensitivity.
引文
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