HPV阳性宫颈癌组织中IGF2BP2和RPRD1B的表达水平及临床价值研究

Expression and Clinical Value of IGF2BP2 and RPRD1B in HPV Positive Cervical Cancer Tissues

目的 研究人乳头瘤病毒(human papilloma virus,HPV)阳性宫颈癌组织中胰岛素样生长因子2结合蛋白2(insulin-like growth factor2 binding protein 2,IGF2BP2)与细胞核前mRNA结构域调节因子1B(regulatory nuclear pre-mRNA domain containing 1B,RPRD1B)的表达及临床价值。方法 选取自2018年1月~2019年1月期间于南通市海门区人民医院诊治的82例HPV阳性宫颈癌患者的癌组织和癌旁组织,以41例HPV阴性宫颈癌组织为对照。应用免疫组织化学分析组织中IGF2BP2,RPRD1B蛋白表达。Spearman秩相关分析IGF2BP2与RPRD1B蛋白表达的相关性。Kaplan-Meier生存分析IGF2BP2,RPRD1B蛋白表达对生存预后的影响。COX比例风险模型分析影响HPV阳性宫颈癌患者生存预后的因素。结果 HPV阳性癌组织IGF2BP2,RPRD1B蛋白阳性率高于HPV阴性癌组织(67.07%vs 9.76%,6.10%)及癌旁正常组织(70.73%vs 17.07%,7.32%),差异具有统计学意义(χ^(2)=35.978,65.705;31.582,62.290,均P<0.05)。IGF2BP2与RPRD1B蛋白表达呈显著正相关(r=0.717,P<0.05)。肿瘤FIGO分期ⅡA期、伴淋巴结转移HPV阳性宫颈癌组织中IGF2BP2(82.61%,90.63%),RPRD1B(86.95%,93.75%)蛋白阳性率分别高于ⅠA~ⅠB期(47.22%,52.00%)、无淋巴结转移组织(50.00%,56.00%),差异均具有统计学意义(χ^(2)=11.450~13.432,均P<0.05)。IGF2BP2阳性组三年累积生存率低于IGF2BP2阴性组(65.45%vs 88.89%)、RPRD1B阳性组三年累积生存率低于RPRD1B阴性组(65.32%vs 91.67%),差异具有统计学意义(Log Rankχ^(2)=6.487,5.192,均P<0.05)。FIGO分期ⅡA期(OR=1.579,95%CI=1.042~2.393)、并发淋巴结转移(OR=1.960,95%CI=1.180~3.256),IGF2BP2阳性(OR=1.786,95%CI=1.226~2.602)和RPRD1B阳性(OR=1.602,95%CI=1.119~2.293)是影响HPV阳性宫颈癌患者生存预后的独立危险因素。结论 宫颈癌中IGF2BP2和RPRD1B表达升高,两者与FIGO分期、淋巴结转移有关,是影响HPV阳性宫颈癌患者预后的独立危险因素。

Objective To study the expression and clinical significance of insulin-like growth factor 2 binding protein 2(IGF2BP2)and regulatory nuclear pre-mRNA domain containing 1B(RPRD1B)in HPV-positive cervical cancer tissues.Methods From January 2018 to January 2019,82 cases of HPV-positive cervical cancer tissues and paracancerous tissues collected in Nantong Haimen District People’s Hospital were selected as the study subjects,and 41 cases of HPV-negative cervical cancer tissues were selected as the control.Immunohistochemistry was used to analyze the expression of IGF2BP2 and RPRD1B protein in tissues.Spearman rank correlation analysis was used to analyze the correlation between IGF2BP2 and RPRD1B protein expression.Kaplan-Meier survival analysis was used to analyze the effect of IGF2BP2,RPRD1B protein expression on survival prognosis in HPV-positive cervical cancer patients.COX proportional risk model was used to analyze factors affecting the survival and prognosis of HPV positive cervical cancer patients.Results The positive rate of IGF2BP2 and RPRD1B protein in HPV-positive cancer tissue was significantly higher than that in HPV-negative cancer tissue(67.07%vs 9.76%,6.10%)and adjacent normal tissue(70.73%vs 17.07%,7.32%),and the differences were statistically significant(χ^(2)=35.978,65.705;31.582,69.290,all P<0.05).IGF2BP2 was positively correlated with RPRD1B protein expression(r=0.717,P<0.05).The positive rates of IGF2BP2(82.61%,90.63%)and RPRD1B(86.95%,93.75%)protein expression in cervical cancer tissues with FIGO stage IIA and HPV positive lymph node metastasis were higher than those in stage IA to stage IB(47.22%,52.00%)and tissues without lymph node metastasis(50.00%,56.00%),and the differences were statistically significant(χ^(2)=11.450~13.432,all P<0.05).The 3-year cumulative survival rates of patients in the IGF2BP2 positive expression group and RPRD1B positive expression group were lower than those in the IGF2BP2 negative expression group(65.45%vs 88.89%)and RPRD1B negative expression group(65.32%vs 91.67%),respectively(Log Rankχ^(2)=6.487,5.192,P<0.05).FIGO stageⅡA(OR=1.579,95%CI=1.042~2.393),combined with lymph node metastasis(OR=1.960,95%CI=1.180~3.256),IGF2BP2 positive(OR=1.786,95%CI=1.226~2.602),RPRD1B positive(OR=1.602,95%CI=1.119~2.293)were independent risk factors affecting the survival and prognosis of HPV-positive cervical cancer patients.Conclusion The increased expression of IGF2BP2 and RPRD1B in cervical cancer were related to FIGO stage and lymph node metastasis,and both of them were independent risk factors affecting the prognosis of HPV-positive cervical cancer patients.