Clinical Research Department, Pasteur Institute of Iran, Tehran, Iran.
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
BMC Infect Dis. 2019 Feb 12;19(1):142. doi: 10.1186/s12879-019-3780-2.
Among different types of human papillomavirus (HPV), types 16 and 18 were known to be high-risk agents causing mainly cervical cancer. Up to now, the potential of HPV E7 protein has been proved as a diagnostic marker of cervical cancer. Moreover, the levels of anti-heat shock protein (Hsp) and anti-high mobility group box-1 (HMGB1) antibodies in cancer patients have been useful in tumor diagnosis. The goal of the present study was to determine the efficiency of the potential serologic markers including HPV E7, Hsp20, Hsp27 proteins and Hp91 peptide in Iranian HPV-exposed women, for the first time.
At first, the recombinant HPV E7, Hsp20 and Hsp27 proteins were expressed in E. coli system, and purified by affinity chromatography under native conditions. Then, antibody responses were detected against the recombinant proteins as well as Hp91 peptide as potential markers in 49 Iranian women who were seropositive for HPV-16 and 18 L1 capsids (i.e., HPV-exposed women) and 49 controls using indirect ELISA.
Our data indicated that the seroreactivities of women exposed to HPV16, HPV18 and both of them against the recombinant E7, Hsp20, Hsp27 proteins and Hp91 peptide were significantly higher than those in control group (p < 0.05 for HPV16 or HPV18; p < 0.01 for both of them versus all markers). HPV-exposed women with high antibody responses to HPV-16 and 18 L1 capsids as a commercial biomarker had significant seroreactivity to HPV-16 and 18 E7 and Hsp27 (p < 0.05). The recombinant E7 and Hsp27 proteins showed higher efficiency than Hsp20 and Hp91 for detection of individuals exposed to HPV infections (p < 0.05).
Generally, the levels of serum E7 and Hsp27 were increased in HPV-16 and 18 L1- seropositive women suggesting their potential value as a diagnostic marker for HPV infections.
在不同类型的人乳头瘤病毒（HPV）中，16 型和 18 型被认为是导致主要宫颈癌的高危因素。到目前为止，HPV E7 蛋白已被证明是宫颈癌的诊断标志物。此外，癌症患者体内抗热休克蛋白（Hsp）和高迁移率族蛋白 1（HMGB1）抗体的水平在肿瘤诊断中很有用。本研究的目的是首次确定包括 HPV E7、Hsp20、Hsp27 蛋白和 Hp91 肽在内的潜在血清学标志物在伊朗 HPV 暴露女性中的效率。
首先，在大肠杆菌系统中表达 HPV E7、Hsp20 和 Hsp27 重组蛋白，并在天然条件下通过亲和层析进行纯化。然后，使用间接 ELISA 在 49 名伊朗 HPV-16 和 18 型 L1 衣壳血清阳性（即 HPV 暴露女性）和 49 名对照女性中检测针对重组蛋白以及 Hp91 肽的抗体反应，作为潜在标志物。
我们的数据表明，暴露于 HPV16、HPV18 或两者的女性对重组 E7、Hsp20、Hsp27 蛋白和 Hp91 肽的血清反应性明显高于对照组（HPV16 或 HPV18 为 p<0.05；两者均高于所有标志物为 p<0.01）。对 HPV-16 和 18 L1 衣壳作为商业生物标志物具有高抗体反应性的 HPV 暴露女性对 HPV-16 和 18 E7 和 Hsp27 具有显著的血清反应性（p<0.05）。重组 E7 和 Hsp27 蛋白在检测 HPV 感染个体方面比 Hsp20 和 Hp91 具有更高的效率（p<0.05）。
一般来说，HPV-16 和 18 L1 血清阳性女性的血清 E7 和 Hsp27 水平升高，表明其作为 HPV 感染诊断标志物的潜在价值。
