宫颈癌放化疗患者DNA-PKcs表达及其预后关系研究
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摘要
目的探讨宫颈癌放化疗患者组织中DNA依赖性蛋白激酶(DNA-depended protein kinase,DNA-PK)的表达及与预后关系。方法选Ⅱb～Ⅲb期宫颈癌患者109例,术前放化疗,14 d后行根治术,据术后病理放疗反应分为病理缓解组(pCR组)及病理无缓解组(non-pCR组);免疫组化SP法检测DNA-PKcs蛋白在宫颈癌组织中的表达;分析其与生存期的关系。结果 pCR组的DNA-PK阳性率(56/85,65.8%)低于non-pCR组(18/24,75.0%),差异具有统计学意义(X~2=8.06,P=0.04)。DNA-PK阳性表达患者的1、3和5年生存率低于阴性表达者,差异有统计学意义(P<0.05)。多因素Cox回归分析显示,影响宫颈癌患者5年生存结局的独立因素包括DNA-PK蛋白(+++)表达(P=0.002)、分化程度(P=0.036)、浸润深度(P=0.001)和远处转移(P=0.002)。结论 DNA-PK可作为宫颈癌放疗敏感性的预测指标,高表达者预后更差。
Objective To investigate the expression of DNA-depended protein kinase(DNA-PK) and its relationship with prognosis in cervical cancer patients undergoing radiotherapy and chemotherapy. Methods 109 cervical cancer patients, stage Ⅱb～Ⅲb, were treated with preoperative radiotherapy and chemotherapy, followed by radical surgery. According to postoperative pathological radiotherapy reaction, were divided into pathologic complete remission(pCR) and non-pathologic complete remission(non-pCR). The immunohistochemical SP method was used to detect the expression of DNA-PKcs protein in cervical cancer tissue, and the relationship with survival time was analyzed. Results The positive rate of DNA-PK in group pCR(56/85, 65.8%) was lower than that in group non-pCR(18/24, 75%)(χ~2=8.06,P=0.04). The 1, 3, and 5 years survival rates of patients with positive DNA-PK expression were lower than those with negative expression(P<0.05). Multivariate Cox regression analysis showed that the independent factors affecting the 5 year survival of patients with cervical cancer included DNA-PK(+ + +) expression, degree of differentiation(P=0.036), depth of infiltration(P=0.001) and distant metastasis(P=0.002). Conclusions DNA-PK can be used as a predictor of radiosensitivity in cervical cancer, and patients with high expression may have worse prognosis.
Objective To investigate the expression of DNA-depended protein kinase(DNA-PK) and its relationship with prognosis in cervical cancer patients undergoing radiotherapy and chemotherapy. Methods 109 cervical cancer patients, stage Ⅱb～Ⅲb, were treated with preoperative radiotherapy and chemotherapy, followed by radical surgery. According to postoperative pathological radiotherapy reaction, were divided into pathologic complete remission(pCR) and non-pathologic complete remission(non-pCR). The immunohistochemical SP method was used to detect the expression of DNA-PKcs protein in cervical cancer tissue, and the relationship with survival time was analyzed. Results The positive rate of DNA-PK in group pCR(56/85, 65.8%) was lower than that in group non-pCR(18/24, 75%)(χ~2=8.06,P=0.04). The 1, 3, and 5 years survival rates of patients with positive DNA-PK expression were lower than those with negative expression(P<0.05). Multivariate Cox regression analysis showed that the independent factors affecting the 5 year survival of patients with cervical cancer included DNA-PK(+ + +) expression, degree of differentiation(P=0.036), depth of infiltration(P=0.001) and distant metastasis(P=0.002). Conclusions DNA-PK can be used as a predictor of radiosensitivity in cervical cancer, and patients with high expression may have worse prognosis.
引文
[1] Minig L,Patrono MG,Romero N,et al.Different strategies of treatment for uterine cervical carcinoma stage IB2-IIB[J].World J Clin Oncol,2014,5(2):86-92.
[2] Ho CK,Kornaga EN,Klimowicz AC,et al.Expression of DNA damage response proteins in cervical cancer patients treated with radical chemoradiotherapy[J].Gynecol Oncol,2017,145(1):176-184.
[3] Wieringa HW,Zee AG,Vries EG,et al.Breaking the DNA damage response to improve cervical cancer treatment[J].Cancer Treat Rev,2016,42(2):30-40.
[4] Mladenov E,Magin S,Soni A,et al.DNA double-strand break repair as determinant of cellular radiosensitivity to killing and target in radiation therapy[J].Front Oncol,2013,10(3):113-120.
[5] Srivastava M,Raghavan SC.DNA double-strand break repair inhibitors as cancer therapeutics [J].Chem Biol,2015,22(1):17-29.
[6] Jette N,Lees-Miller SP.The DNA-dependent protein kinase:A multifunctional protein kinase with roles in DNA double strand break repair and mitosis[J].Prog Biophys Mol Biol,2015,117(2-3):194-205.
[7] Gustafsson AS,Abramenkovs A,Stenerl B.Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair[J].Mutat Res,2014,769(13):1-10.
[8] Liu Y1,Zhang L,Liu Y,et al.DNA-PKcs deficiency inhibits glioblastoma cell-derived angiogenesis after ionizing radiation[J].J Cell Physiol,2015,230(5):1094-1103.
[9] Kawano M,Mabuchi S,Matsumoto Y,et al.Prognostic significance of pretreatment thrombocytosis in cervical cancer patients treated with definitive radiotherapy[J].Int J Gynecol Cancer,2015,25(9):1656-1662.
[10] Khalil J,El Kacemi H,Afif M,et al.Five years' experience treating locally advanced cervical cancer with concurrent chemoradiotherapy:results from a single institution[J].Arch Gynecol Obstet,2015,292(5):1091-1099.
[11] Goodwin JF,Knudsen KE.Beyond DNA repair:DNA-PK function in cancer[J].Cancer Discov,2014,4(10):1126-1139.
[12] Sun J,Yang X,Ji H,et al.Expression and significance of DNA-dependent protein kinase in human laryngeal squamous cell carcinoma[J].Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi,2014,28(21):1641-1644.
[13] Vávrová J,Zárybnická L,Jo P,et al.Comparison of the radiosensitizing effect of atr,atm and dna-pk kinase inhibitors on cervical carcinoma cells[J].Folia Biol(Praha),2016,62(4):167-174.
[2] Ho CK,Kornaga EN,Klimowicz AC,et al.Expression of DNA damage response proteins in cervical cancer patients treated with radical chemoradiotherapy[J].Gynecol Oncol,2017,145(1):176-184.
[3] Wieringa HW,Zee AG,Vries EG,et al.Breaking the DNA damage response to improve cervical cancer treatment[J].Cancer Treat Rev,2016,42(2):30-40.
[4] Mladenov E,Magin S,Soni A,et al.DNA double-strand break repair as determinant of cellular radiosensitivity to killing and target in radiation therapy[J].Front Oncol,2013,10(3):113-120.
[5] Srivastava M,Raghavan SC.DNA double-strand break repair inhibitors as cancer therapeutics [J].Chem Biol,2015,22(1):17-29.
[6] Jette N,Lees-Miller SP.The DNA-dependent protein kinase:A multifunctional protein kinase with roles in DNA double strand break repair and mitosis[J].Prog Biophys Mol Biol,2015,117(2-3):194-205.
[7] Gustafsson AS,Abramenkovs A,Stenerl B.Suppression of DNA-dependent protein kinase sensitize cells to radiation without affecting DSB repair[J].Mutat Res,2014,769(13):1-10.
[8] Liu Y1,Zhang L,Liu Y,et al.DNA-PKcs deficiency inhibits glioblastoma cell-derived angiogenesis after ionizing radiation[J].J Cell Physiol,2015,230(5):1094-1103.
[9] Kawano M,Mabuchi S,Matsumoto Y,et al.Prognostic significance of pretreatment thrombocytosis in cervical cancer patients treated with definitive radiotherapy[J].Int J Gynecol Cancer,2015,25(9):1656-1662.
[10] Khalil J,El Kacemi H,Afif M,et al.Five years' experience treating locally advanced cervical cancer with concurrent chemoradiotherapy:results from a single institution[J].Arch Gynecol Obstet,2015,292(5):1091-1099.
[11] Goodwin JF,Knudsen KE.Beyond DNA repair:DNA-PK function in cancer[J].Cancer Discov,2014,4(10):1126-1139.
[12] Sun J,Yang X,Ji H,et al.Expression and significance of DNA-dependent protein kinase in human laryngeal squamous cell carcinoma[J].Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi,2014,28(21):1641-1644.
[13] Vávrová J,Zárybnická L,Jo P,et al.Comparison of the radiosensitizing effect of atr,atm and dna-pk kinase inhibitors on cervical carcinoma cells[J].Folia Biol(Praha),2016,62(4):167-174.