ICAM-3、HIF-1蛋白表达水平与高原女性宫颈癌放疗抵抗的相关性研究
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摘要
目的探讨细胞间黏附分子3(intercellular cell adhesion molecule-3,ICAM-3)、缺氧诱导因子1(hypoxia inducible factor-1,HIF-1)蛋白表达水平与高原女性宫颈癌放疗抵抗的相关性。方法选取宫颈鳞癌患者58例,确诊后均给予根治性放疗及同步化疗。于治疗前活组织检查取得宫颈鳞癌组织,检测组织标本的ICAM-3、HIF-1表达,并参照WHO实体瘤客观疗效标准评估疗效。根据治疗效果将患者分为放疗抵抗组与放疗敏感组。比较放疗抵抗组与放疗敏感组ICAM-3、HIF-1表达以及不同临床分期、组织学分级和淋巴结转移中ICAM-3、HIF-1表达情况。结果 58例患者中放疗敏感组39例、放疗抵抗组19例。2组ICAM-3、HIF-1表达分布差异有统计学意义,放疗敏感组ICAM-3、HIF-1阳性表达率低于放疗抵抗组(P<0.05)。高分化患者ICAM-3、HIF-1阳性率高于低、中分化患者,淋巴结阳性患者ICAM-3、HIF-1阳性率高于淋巴结阴性患者(P<0.05)。不同临床分期患者ICAM-3、HIF-1阳性率差异无统计学意义(P>0.05)。Kendall′s tau-b相关分析结果显示,ICAM-3表达与组织学分化(b=0.529,P=0.007)、淋巴结转移(b=0.510,P=0.012)呈正相关,HIF-1表达与组织学分化(b=0.489,P=0.018)、淋巴结转移(b=0.535,P=0.003)呈正相关。结论 ICAM-3、HIF-1蛋白表达水平越高,高原地区宫颈癌患者出现放疗抵抗的概率越高,且ICAM-3、HIF-1蛋白表达与组织学分级、淋巴结转移呈正相关,可作为放疗敏感性的预测指标。
Objective To investigate the relationship between the expression levels of intercellular cell adhesion molecule-3(ICAM-3),hypoxia inducible factor-1(HIF-1)and the radiotherapy resistance of cervical cancer in plateau.Methods A total of 58 patients with cervical squamous cell carcinoma were selected,and radical radiotherapy and concurrent chemotherapy were given after diagnosis.Biopsy of cervical squamous cell carcinoma was obtained before biopsy,and the expression of ICAM-3 and HIF-1 in tissue samples were detected.The efficacy was evaluated according to the objective efficacy criteria of WHO solid tumors.The patients were divided into radiotherapy resistance group and radiotherapy sensitive group according to the treatment effect.The expressions of ICAM-3 and HIF-1 expression between radiotherapy resistant group and radiotherapy sensitive group,the expression of ICAM-3 and HIF-1 in different clinical stages,histological grades and lymph node metastasis were compared.Results Among the 58 patients,39 cases were in radiotherapy-sensitive group and 19 cases were in radiotherapy-resistant group.The difference of distribution of ICAM-3 and HIF-1 expression in the two groups were statistically significant.The positive expression rate of ICAM-3 and HIF-1 in radiotherapy sensitive group were lower than those in radiotherapy resistance group(P<0.05).The positive rate of ICAM-3 and HIF-1 in well-differentiated patients were higher than those in low-and moderate-differentiated patients.The positive rate of ICAM-3 and HIF-1 in lymph node-positive patients were higher than those in node-negative patients(P<0.05).There were no significant difference in the expression of ICAM-3 and HIF-1 between different clinical stages(P>0.05).Kendall′s tau-b correlation analysis showed that the expression of ICAM-3 were positively correlated with histological differentiation(b=0.529,P=0.007),lymph node metastasis(b=0.510,P=0.012),the expression of HIF-1 were also positively correlated with histological differentiation(b=0.489,P=0.018)and lymph node metastasis(b=0.535,P=0.003).Conclusion The higher the expression level of ICAM-3 and HIF-1 protein,the higher the probability of radiotherapy resistance in cervical cancer patients in high altitude areas,and the positive expression of ICAM-3 and HIF-1 protein expression were positively correlated with histological grade and lymph node metastasis,can be used as a predictor of radiotherapy sensitivity.
Objective To investigate the relationship between the expression levels of intercellular cell adhesion molecule-3(ICAM-3),hypoxia inducible factor-1(HIF-1)and the radiotherapy resistance of cervical cancer in plateau.Methods A total of 58 patients with cervical squamous cell carcinoma were selected,and radical radiotherapy and concurrent chemotherapy were given after diagnosis.Biopsy of cervical squamous cell carcinoma was obtained before biopsy,and the expression of ICAM-3 and HIF-1 in tissue samples were detected.The efficacy was evaluated according to the objective efficacy criteria of WHO solid tumors.The patients were divided into radiotherapy resistance group and radiotherapy sensitive group according to the treatment effect.The expressions of ICAM-3 and HIF-1 expression between radiotherapy resistant group and radiotherapy sensitive group,the expression of ICAM-3 and HIF-1 in different clinical stages,histological grades and lymph node metastasis were compared.Results Among the 58 patients,39 cases were in radiotherapy-sensitive group and 19 cases were in radiotherapy-resistant group.The difference of distribution of ICAM-3 and HIF-1 expression in the two groups were statistically significant.The positive expression rate of ICAM-3 and HIF-1 in radiotherapy sensitive group were lower than those in radiotherapy resistance group(P<0.05).The positive rate of ICAM-3 and HIF-1 in well-differentiated patients were higher than those in low-and moderate-differentiated patients.The positive rate of ICAM-3 and HIF-1 in lymph node-positive patients were higher than those in node-negative patients(P<0.05).There were no significant difference in the expression of ICAM-3 and HIF-1 between different clinical stages(P>0.05).Kendall′s tau-b correlation analysis showed that the expression of ICAM-3 were positively correlated with histological differentiation(b=0.529,P=0.007),lymph node metastasis(b=0.510,P=0.012),the expression of HIF-1 were also positively correlated with histological differentiation(b=0.489,P=0.018)and lymph node metastasis(b=0.535,P=0.003).Conclusion The higher the expression level of ICAM-3 and HIF-1 protein,the higher the probability of radiotherapy resistance in cervical cancer patients in high altitude areas,and the positive expression of ICAM-3 and HIF-1 protein expression were positively correlated with histological grade and lymph node metastasis,can be used as a predictor of radiotherapy sensitivity.
引文
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[13]黄平,张立民,黄冬冬,等.缺氧诱导因子1α在促卵泡激素促进卵巢癌SKOV3细胞增殖与侵袭中的作用[J].河北医科大学学报,2016,37(4):450-453.
[14]应申鹏,曹学全,王赛赛,等.缺氧诱导因子-1α在宫颈癌放疗过程中的表达[J].现代实用医学,2017,29(5):661-663.
[15]张德太,左曙蓉,杨文,等.siRNA沉默转酮醇酶样基因1下调人宫颈癌细胞HIF-1α表达及糖酵解关键酶活性[J].中国病理生理杂志,2014,30(1):72-76.
[16]王芳,尹立勇,娄娟,等.HIF-1α及其靶基因在宫颈癌中的表达[J].河北医科大学学报,2017,38(7):764-769.
[17]宋妮娜,瞿全新.宫颈上皮内瘤变分子生物学指标的研究进展[J].国际妇产科学杂志,2016,43(5):524-527.
[18]赵小玲,孔为民.宫颈癌放疗敏感性相关基因研究进展[J].医学综述,2018,24(10):1883-1887.
[2]罗昊翔.HIF-1在肿瘤形成中的作用及有氧运动对肿瘤的防治机制[J].基因组学与应用生物学,2015,34(12):2570-2574.
[3]任伟,闫婧,钱晓萍,等.食管癌放化疗后近期疗效评价标准的研究进展[J].中华肿瘤杂志,2014,36(9):641-644.
[4]马海丹,刘灿华,麦丽兰,等.182例宫颈癌患者生存情况及其影响因素分析[J].现代医学,2017,45(1):90-93.
[5]张冬娟.局部晚期宫颈癌的放射治疗进展[J].重庆医学,2017,46(22):3147-3150.
[6]戴蜜蜜,耿筱虹.宫颈癌放疗抵抗相关因素研究进展[J].中国现代医生,2017,55(26):165-168.
[7]丁立新,赵现哲,姜晓燕,等.宫颈癌辐射敏感性相关基因的研究进展[J].癌变·畸变·突变,2017,29(5):394-396,401.
[8]沙红兰,何陈云,李咏,等.ICAM-3蛋白表达在预测宫颈癌放射抵抗性中的价值[J].浙江临床医学,2016,18(9):1575-1577.
[9]梁秋实,任卫东.PI3K信号通路抑制剂在人乳腺癌细胞侵袭的作用及可能机制[J].解剖科学进展,2015,21(3):249-251,255.
[10]宁思思,谢莹.DC-SIGN与肿瘤关系的研究进展[J].生命科学研究,2015,19(3):252-257.
[11]马超,赵继志,张韬,等.细胞黏附分子-1和淋巴细胞功能相关抗原在口腔鳞癌中的表达及其临床意义[J].中国药物与临床,2015,15(9):1337-1339.
[12]娄英,梁文倩.宫颈癌患者HIF-1α、VEGF、MVD、CXCL12/CXCR4的表达及其预后研究[J].中国妇幼保健,2016,31(20):4135-4138.
[13]黄平,张立民,黄冬冬,等.缺氧诱导因子1α在促卵泡激素促进卵巢癌SKOV3细胞增殖与侵袭中的作用[J].河北医科大学学报,2016,37(4):450-453.
[14]应申鹏,曹学全,王赛赛,等.缺氧诱导因子-1α在宫颈癌放疗过程中的表达[J].现代实用医学,2017,29(5):661-663.
[15]张德太,左曙蓉,杨文,等.siRNA沉默转酮醇酶样基因1下调人宫颈癌细胞HIF-1α表达及糖酵解关键酶活性[J].中国病理生理杂志,2014,30(1):72-76.
[16]王芳,尹立勇,娄娟,等.HIF-1α及其靶基因在宫颈癌中的表达[J].河北医科大学学报,2017,38(7):764-769.
[17]宋妮娜,瞿全新.宫颈上皮内瘤变分子生物学指标的研究进展[J].国际妇产科学杂志,2016,43(5):524-527.
[18]赵小玲,孔为民.宫颈癌放疗敏感性相关基因研究进展[J].医学综述,2018,24(10):1883-1887.