宫颈病变中转录因子NF‐κB家族P50、IκB‐α表达与HPV16阳性宫颈癌的关系分析

Relationship between the expression of NF⁃κB family P50 and IκB⁃αin cervical lesions and HPV16⁃positive cervical cancer

目的分析宫颈病变中转录因子核因子‑κB(NF‑κB)家族P50、NF‑κB抑制蛋白‑α(IκB‑α)表达与人乳头瘤病毒16(HPV16)阳性宫颈癌的关系。方法收集南通大学附属肿瘤医院2017年3月至2019年2月收治的106例HPV16阳性宫颈癌、52例高级别鳞状上皮内瘤变(HSIL)、43例低级别鳞状上皮内瘤变(LSIL)患者的宫颈组织标本及同期因子宫腺肌症行全子宫切除术的80例患者正常宫颈组织标本。采用免疫组化法测定不同组织标本中NF‑κB P50和IκB‑α表达情况。比较NF‑κB P50、IκB‑α在不同宫颈组织中的表达情况。分析NF‑κB P50和IκB‑α表达水平与宫颈癌患者病理特征的关系。使用Cox回归分析影响HPV16阳性宫颈癌患者预后的因素。分析NF‑κB P50、IκB‑α表达水平与HPV16阳性宫颈癌患者预后的关系。结果NF‑κB P50阳性表达率、IκB‑α阴性表达率表现为宫颈癌组织>HSIL组织>LSIL组织>正常宫颈组织(P<0.01)。肿瘤最大径>4 cm、临床分期Ⅲ/Ⅳ期、有淋巴结转移、低分化、脉管侵犯的HPV16阳性宫颈癌患者癌组织中NF‑κB P50阳性表达率、IκB‑α阴性表达率高于肿瘤最大径<4 cm、临床分期Ⅰ/Ⅱ期、无淋巴结转移、中/高分化、无脉管侵犯的HPV16阳性宫颈癌患者,差异有统计学意义(P<0.05)。Cox回归分析显示,临床分期(OR=2.546,95%CI:1.054~3.672)、淋巴结转移(OR=2.734,95%CI:1.469~4.183)、分化程度(OR=3.257,95%CI:2.015~6.432)、NF‑κB P50阳性表达(OR=4.025,95%CI:2.765~8.436)、IκB‑α阴性表达(OR=4.368,95%CI:3.104~10.254)均是HPV16阳性宫颈癌患者预后的独立影响因素(P<0.05)。截至随访结束,NF‑κB P50阳性、NF‑κB P50阴性的HPV16阳性宫颈癌患者总存活率分别为73.68%、92.59%,NF‑κB P50阳性表达患者与NF‑κB P50阴性表达患者生存曲线比较,差异有统计学意义(P<0.05)。IκB‑α阳性、IκB‑α阴性的HPV16阳性宫颈癌患者总存活率分别为100.00%、76.34%,IκB‑α阳性表达患者与IκB‑α阴性表达患者生存曲线比较,差异有统计学意义(P<0.05)。结论HPV16阳性宫颈癌患者癌组织中NF‑κB P50阳性表达率、IκB‑α阴性表达率较高,NF‑κB P50、IκB‑α表达与HPV16阳性宫颈癌临床病理特征及预后均具有一定的相关性。

Objective To analyze the relationship between the expression of nuclear factorκB(NF‑κB)family of transcription factors(P50)and NF‑κB inhibitory protein‑α(IκB‑α)in cervical lesions and human papilloma virus 16(HPV16)‑positive cervical cancer.Methods Cervical tissue samples were collected from 106 patients with HPV16‑positive cervical cancer,52 patients with high‑grade squamous intraepithelial neoplasia(HSIL),and 43 patients with low‑grade squamous intraepithelial neoplasia(LSIL)admitted to Tumor Hospital Affilated to Natong University from March 2017 to February 2019.Normal cervical tissue samples were collected from 80 patients who underwent total hysterectomy for adenomyosis during the same period.The expression levels of NF‑κB P50 and IκB‑αin different cervical tissue samples were determined by immunohistochemistry.The expression of NF‑κB P50 and IκB‑αin different cervical tissue was compared.The relationship between NF‑κB P50 and IκB‑αexpression levels and pathological features of cervical cancer patients was investigated.Cox regression analysis was used to assess the factors affecting the prognosis of patients with HPV16‑positive cervical cancer.The relationship between NF‑κB P50 and IκB‑αexpression levels and the prognosis of HPV16‑positive cervical cancer patients was analyzed.Results The positive expression rate of NF‑κB P50 and the negative expression rate of IκB‑αfrom high to low was:cervical cancer tissue,HSIL tissue,LSIL tissue,and normal cervical tissue(P<0.01).The positive expression rate of NF‑κB P50 and the negative expression rate of IκB‑αin HPV16‑positive cervical cancer patients with the largest tumor diameter≥4 cm,clinical stage III/IV,lymph node metastasis,poorly differentiated,and vascular invasion were significantly higher than those in the patients with the tumor largest diameter<4 cm,clinical stage I/II,no lymph node metastasis,moderate/well differentiated,and no vascular invasion(P<0.05).Cox regression analysis showed that clinical stage(OR:2.546,95%CI:1.054‑3.672),lymph node metastasis(OR:2.734,95%CI:1.469‑4.183),degree of differentiation(OR:3.257,95%CI:2.015‑6.432),positive expression of NF‑κB P50(OR:4.025,95%CI:2.765‑8.436),and negative expression of IκB‑α(OR:4.368,95%CI:3.104‑10.254)were independent influence factors for the prognosis of patients with HPV16‑positive cervical cancer factor(P<0.05).By the end of the follow‑up,the overall survival rates of NF‑κB P50 positive patients and NF‑κB P50 negative patients were 73.68%and 92.59%,respectively.There was a statistically significant difference between the survival curves of patients with positive NF‑κB P50 expression and those with negative NF‑κB P50 expression(P<0.05).The overall survival rates of IκB‑αpositive patients and IκB‑αnegative patients were 100.00%and 76.34%,respectively.There was a statistically significant difference between the survival curves of patients with positive IκB‑αprotein expression and those with negative expression of IκB‑αprotein(P<0.05).Conclusion There are high positive expression rate of NF‑κB P50 and high negative expression rate of IκB‑αin the cancer tissue of HPV16‑positive cervical cancer patients.The expression of NF‑κB P50 and IκB‑αhas a certain correlation with clinicopathological characteristics and prognosis of HPV16‑positive cervical cancer patients.