探讨趋化因子受体(CXCR)7与人乳头瘤病毒(HPV)-16、-18在宫颈癌及其癌前病变中的相关性。

选择2011年3月至2013年3月在珠海市人民医院进行手术治疗时切除组织经病理学检查确诊为宫颈癌的59例患者(纳入宫颈癌组)，确诊为宫颈上皮内瘤变(CIN)的86例患者(纳入CIN组)，以及因其他疾病切除正常子宫颈的20例患者(纳入对照组)为研究对象。采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结(SP)法检测3组患者宫颈组织的CXCR7表达水平及其阳性率。采用实时定量PCR方法检测3组患者宫颈组织中HPV-16、-18 DNA表达量。采用Western blotting方法检测3组患者宫颈组织中CXCR7和基质细胞衍生因子(SDF)-1蛋白表达量，并进行CXCR7表达量和HPV-16、-18 DNA表达量的相关性分析。3组患者的年龄等基本临床资料比较，差异无统计学意义(P>0.05)。

①宫颈癌组及CIN组患者宫颈组织中，CXCR7阳性率均显著高于对照组，并且差异有统计学意义(χ²＝37.77，P<0.001；χ²＝6.68，P＝0.010)。②HPV-16 DNA在CIN Ⅰ、Ⅱ、Ⅲ和宫颈癌组织中的表达量，分别为对照组宫颈组织的(1.50±0.05)倍、(2.87±0.09)倍、(3.17±0.12)倍与(6.41±0.20)倍；在CINⅢ和宫颈癌组织中，HPV-16 DNA表达量显著高于对照组，并且差异有统计学意义(t＝2.15，P＝0.042；t＝3.11，P＝0.003)。HPV-18 DNA在CIN Ⅰ、Ⅱ、Ⅲ和宫颈癌组织中的表达量，分别是对照组宫颈组织中的(1.56±0.07)倍、(2.45±0.11)倍、(3.89±0.16)倍与(6.12±0.17)倍；在CIN Ⅲ和宫颈癌组织中，HPV-18 DNA表达量显著高于对照组，并且差异有统计学意义(t＝2.21，P＝0.024；t＝3.03，P＝0.004)。③Western blotting检测结果表明，SDF-1和CXCR7随着宫颈组织病变程度的加深，其表达量随之上升，并且CXCR7表达量与HPV-16、-18 DNA表达量均呈正相关关系(r＝0.74、0.78，P<0.001)。

CXCR7可能促进高危型HPV引起宫颈癌的进程。

To investigate the correlation between human papillomavirus (HPV) -16, -18 and C-X-C chemokine receptor (CXCR) 7 in cervical cancer and intraepithelial neoplasm.

A total of 59 patients who underwent cervix resection and were diagnosed as cervical cancer by pathological detection, 86 patients who under went cervix resection and were diagnosed as cervical intraepithelial neoplasm (CIN) by pathological detection and 20 patients who underwent cervix resection due to other diseases were collected as study subjects in the Zhuhai People′s Hospital from March 2011 to March 2013. They were enrolled into cervical cancer group (n=59), CIN group (n=86) and control group (n=20), respectively. The expression of CXCR7 was examined by immunohistochemical, and the difference of CXCR7 expression among 3 groups were analyzed. Subsequently, the relative expression of HPV-16 DNA and HPV-18 DNA were verified with quantitative real-time PCR. Eventually, the protein expression profile of CXCR7 and stromal cell-derived factor (SDF)-1 were tested by Western blotting among 3 groups, and then the correlation analysis were performed between the expression HPV-16 DNA, HPV-18 DNA and CXCR7. There were no significant differences between two groups in age and other general clinical data (P>0.05).

①The expression positive rates of CXCR7 in cervical tissues of cervical cancer group and CIN group both were significantly higher than that of control group, which were 88.1% (52/59) vs 15.0% (3/20) and 46.5% (40/86) vs 15.0% (3/20), and both the differences were statistically significant (χ²=37.77, P<0.001; χ²=6.68, P=0.010). ②The expression of HPV-16 DNA in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ and cervical cancer tissues were (1.50±0.05) times, (2.87±0.09) times, (3.17±0.12) times and (6.41±0.20) times as much as that in normal cervix tissues, respectively, and the expression of HPV-16 DNA in CIN Ⅲ and cervical cancer tissues both were significantly higher than that in normal cervix tissues, and both the differences were statistically significant (t=2.15, P=0.042; t=3.11, P=0.003). Likewise, the expression of HPV-18 DNA in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ and cervical cancer tissues were (1.56±0.07) times, (2.45±0.11) times, (3.89±0.16) times and (6.12±0.17) times as much as that in normal cervix tissues, respectively, and the expression of HPV-18 DNA in CIN Ⅲ and cervical cancer tissues both were significantly higher than in normal cervix tissues, and both the differences were statistically significant (t=2.21, P=0.024; t=3.03, P=0.004). ③The expression of CXCR7 and SDF-1 increased as the the deterioration of the disease by Western blotting. Not only that, there were positive correlation between CXCR7 expression and HPV-16 DNA (r=0.74, P<0.001), and HPV-18 DNA (r=0.78, P<0.001).

HPV may contribute the progression of cervical cancer induced by high-risk HPV.