HPV-16多肽在前列腺癌患者血清抗体筛查中的应用

Application of HPV-16peptides based microarray technology in the seroscreening of prostate cancer

目的探讨HPV-16感染与前列腺癌的相关性及基于HPV-16多肽微阵列芯片在前列腺癌患者血清筛查中的应用。方法对来自HPV-16病毒的7个蛋白的胞外段序列进行叠瓦式切割,构建基于241条精细多肽库的微阵列芯片,对经病理确诊的72例前列腺癌患者和87例前列腺增生患者行血清学筛查。用微阵列芯片表达差异显著分析法筛选在前列腺癌患者和前列腺增生患者血清中具有差异性表达的多肽(特异性多肽);以受试者工作特征曲线(receiver operator characteristic curve,ROC)评价这些多肽对前列腺癌的诊断价值,并与PSA相比较。结果HPV-16多肽在两组血清中的抗体响应不同,与HPV-16多肽反应的自身抗体既存在于前列腺癌患者中,也存在于前列腺增生患者中。其中存在15条多肽,与之响应的抗体在两组血清中呈差异性表达;对这15条具有潜在诊断价值的多肽进行ROC曲线分析,发现多指标联合的诊断模型具有更高的诊断效率,由15条多肽构成的多指标联合诊断模型ROC曲线下面积为0.772,在最佳临界值的诊断灵敏度为75.3%,特异度为61.8%;PSA的ROC曲线下面积为0.770,在最佳临界值的诊断灵敏度为65.3%,特异度83.9%。结论前列腺癌患者血清中存在HPV-16特异性自身抗体,并可通过HPV-16多肽微阵列技术加以检测。

Objective To investigate the relationship between HPV-16 infection and prostate cancer by using the HPV-16 peptides based microarray in the seroscreening. Methods Antigen se- quences from seven proteins of HPV-16 were cut into 20 mer peptides containing overlaps of 10 ami- no acids, resulting in a total of 241 HPV-16 peptide rnicroarrays. 159 serum samples （72 prostate cancer subjects and 87 BPH samples） were included in the serological search. Significant analysis of microarray was used to identify peptides that performed differential expression between the two groups. Receiver operating characteristic （ROC） analyses were performed to assess the predictive value of the identified peptides when compared with PSA, and a p value 〈 0.05 was considered sta- tistically significant. Results HPV-16 related antibodies existing in both prostate cancers and BPH patients, specific antibodies-epitope interactions performed different in the two groups. 15 peptides were identified as statistically significantly higher responding peptides in prostate cancer samples. ROC analyses showed that the diagnosis model with multi-index combination had higher diagnostic efficiency. The area under the ROC curve was 0.772, with sensitivity of 75.3 % while a specificity of 61.8% when set the cutoff value to 3. Area under the ROC curve of PSA was 0.770, with sensitivity of 65.3% while a specificity of 83.9%. Conclusions Results showed HPV-16 related specific anti bodies exists in prostate cancer and could be detected by HPV-16 based microarray.