宫颈癌患者血清LCN2水平表达与HPV病毒载量及临床分期的相关研究

Correlation of Expression of Serum LCN2 Level with HPV Load and Clinical Stage in Patients with Cervical Cancer

目的 探究宫颈癌患者血清脂质运载蛋白2(lipocalin 2,LCN2)水平,分析其与高危型人乳头瘤病毒(high risk-human papilloma virus,HR-HPV)病毒载量及临床分期的相关性。方法 选取2019年4月~2021年2月淮安市妇幼保健院收治的宫颈癌患者64例为研究对象(宫颈癌组),另选取同期治疗的宫颈上皮内瘤变患者60例(宫颈上皮内瘤变组)和体检健康女性69例(正常对照组)。采用第二代杂交捕获技术(hybrid captureⅡ,HC-Ⅱ)进行HRHPV病毒载量检测,采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测血清LCN2水平,采用Pearson法分析宫颈上皮内瘤变和宫颈癌患者HR-HPV病毒载量与血清LCN2水平相关性;采用受试者工作特征(receiver operating characteristic,ROC)曲线分析HR-HPV病毒载量与血清LCN2水平对宫颈癌的诊断效能。结果 宫颈癌组、宫颈上皮内瘤变组、正常对照组HR-HPV病毒载量(1 173.51±264.37,669.61±123.92,0.52±0.15RLU/CO)及血清LCN2水平(84.16±26.95,43.67±13.82,12.05±4.31pg/ml)依次降低,差异有统计学意义(F=825.576,282.028,均P=0.000)。宫颈上皮内瘤变及宫颈癌患者HR-HPV病毒载量与血清LCN2水平均呈正相关(r=0.386,P=0.002;r=0.375,P=0.003)。HR-HPV病毒载量与血清LCN2水平联合检测对宫颈癌诊断的曲线下面积为0.872(95%CI:0.790~0.928),敏感度和特异度分别为90.19%和83.00%。FIGO分期Ⅰ,Ⅱ和Ⅲ期患者HR-HPV病毒载量(1 018.82±101.27,1 181.64±124.73,1 294.37±113.06RLU/CO)及血清LCN2水平(66.55±10.18,85.05±15.66,98.04±13.07)pg/ml依次明显升高,差异有统计学意义(F=28.574,29.060,均P=0.000);脉管浸润阳性、淋巴结转移患者HR-HPV病毒载量(1 293.51±113.17,1 294.37±113.06RLU/CO)及血清LCN2水平(97.31±18.63,98.04±13.07)pg/ml明显高于脉管浸润阴性(1 101.05±139.84RLU/CO,76.27±12.06pg/ml)和无淋巴结转移患者(1129.23±117.51RLU/CO, 79.14±14.27pg/ml),差异均有统计学意义(F=5.851,4.619,3.927,3.722,均P=0.000)。结论 宫颈癌患者血清LCN2水平明显升高,与HR-HPV病毒载量升高、FIGO分期升高、脉管浸润及淋巴结转移等进展有关,可能作为标志物预示宫颈癌的发生发展。

Objective To investigate the expression level of serum lipocalin 2(LCN2) in patients with cervical cancer, and analyze the correlation between LCN2 and the viral load, clinical stage of high risk-human papilloma virus(HR-HPV). Methods From April 2019 to February 2021, 64 patients with cervical cancer in Huaian Maternal and Child Health Hospital were selected as the study objects(cervical cancer group). In addition, 60 cases of cervical intraepithelial neoplasia treatedin the hospital at the same time(cervical intraepithelial neoplasia group) and 69 healthy women(normal control group) were selected. The second generation hybrid capture Ⅱ(HC-Ⅱ) was used to detect the viral load of HR-HPV, the expression level of serum LCN2 was detected by enzyme-linked immunosorbent assay(ELISA). Pearson method was used to analyze the correlation between HR-HPV load and serum LCN2 level in patients with cervical intraepithelial neoplasia and cervical cancer. In addition, receiver operating characteristic(ROC) curve was used to analyze the diagnostic effcacy of HR-HPV viral load and serum LCN2 level for cervical cancer. Results HR-HPV viral load(1173.51±264.37, 669.61±123.92, 0.52±0.15 RLU/CO) and serum LCN2 level(84.16±26.95, 43.67±13.82, 12.05±4.31 pg/ml) in cervical cancer group, cervical intraepithelial neoplasia group and normal control group decreased in turn, the differences were statistically significant(F=825.576, 282.028, all P=0.000). There was a positive correlation between HR-HPV viral load and serum LCN2 level in cervical intraepithelial neoplasia and cervical cancer(r=0.386, P=0.002;r=0.375, P=0.003). The area under the curve of HR-HPV viral load combined with serum LCN2 level in the diagnosis of cervical cancer was 0.872(95% CI: 0.790 ~ 0.928), the sensitivity and the specificity were 90.19% and 83.00%, respectively. The HR-HPV viral load(1 018.82±101.27, 1 181.64±124.73, 1 294.37±113.06 RLU/CO) and serum LCN2 level(66.55±10.18, 85.05±15.66, 98.04±13.07 pg/ml) in patients with FIGO stage Ⅰ, Ⅱ and Ⅲ were significantly increased in turn, the differences were statistically significant(F=28.574, 29.060, all P=0.000). The HR-HPV viral load and serum LCN2 level in patients with positive vessel infiltration(1 293.51±113.17, 1 294.37±113.06 RLU/CO) and lymph node metastasis(97.31±18.63, 98.04±13.07 pg/ml) were significantly higher than those in patients with negative vessel infiltration(1 101.05±139.84 RLU/CO, 76.27±12.06 pg/ml) and non lymph node metastasis(1 129.23±117.51 RLU/CO, 79.14±14.27 pg/ml), the differences were statistically significant(F=5.851, 4.619, 3.927, 3.722, all P=0.000). Conclusion The level of serum LCN2 in patients with cervical cancer was significantly higher, which was related to the increase of HR-HPV viral load, the increase of FIGO stage, vascular invasion, lymph node metastasis and so on. It may be used as a marker to predict the occurrence and development of cervical cancer.