Ki-67、ERCC1的表达对胃癌新辅助化疗病理学缓解的预测价值
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摘要
[目的]探讨胃癌患者组织中ERCC1、ki-67表达及变化与新辅助化疗(neoadjuvant chemotherapy,NAC)敏感性的关系。[方法]收集126例NAC后行R0切除术的胃癌患者,通过免疫组织化学方法检测患者第1次胃镜取检及术后标本癌组织中ki-67、ERCC1的表达水平,结合相关临床病理因素,采用χ~2检验、多因素Logistic回归及Spearman相关分析法分析数据。[结果]单因素分析显示:T分期、临床分期、ki-67表达、NAC前后ki-67变化及ERCC1表达均与NAC疗效相关(均P<0.05);T分期、ki-67的表达及ERCC1的表达与胃癌患者NAC后病理完全缓解(pathological complete response,pCR)相关(P<0.05);多因素Logistic回归结果显示ki-67表达(OR=7.956,95%CI:1.305～48.492,P=0.025)、NAC前后ki-67变化(OR=6.497,95%CI:1.125～37.528,P=0.036)及ERCC1表达(OR=5.271,95%CI:1.020～27.255,P=0.047)均为NAC疗效的独立影响因素;ki-67(OR=0.260,95%CI:0.080～0.849,P=0.026)及ERCC1(OR=0.264,95%CI:0.078～0.899,P=0.033)的表达为pCR的独立影响因素;且ki-67的表达与ERCC1的表达无相关性(P>0.05)。[结论] Ki-67、ERCC1的表达是胃癌患者NAC疗效的独立预测因子,同时结合其他相关指标,将更有利于指导个体化NAC。
[Purpose] To investigate the expression level of Ki-67 and ERCC1 in patients with gastric cancer undergoing neoadjuvant chemotherapy(NAC). [Methods] One hundred and twenty-six patients with gastric cancer who underwent radical surgery after NAC were enrolled. The expression level of ki67 and ERCC1 in tumor tissues from the gastroscopy and postoperative specimens were detected with immunohistochemistry. The predictive value of Ki67 and ERCC1 expression for NAC response was analyzed by multivariate Logistic regression and Spearman correlation methods.[Results] The univariate analysis showed that response rate after NAC was significantly related to the T stage,clinical stage,ki-67 expression and ki-67 changes after NAC as well as ERCC1 expression(P<0.05);T staging,ki-67 expression and ERCC1 expression were correlated with pathological complete response(pCR) after NAC in gastric cancer patients(P<0.05). Multivariate analysis revealed that Ki-67(OR=7.956,95%CI:1.305 ～48.492,P=0.025),ki-67 changes after NAC(OR=6.497,95%CI:1.125～37.528,P=0.036) and ERCC1(OR=5.271,95%CI:1.020 ～27.255,P=0.047)expression level were the independent predictive factors for response rate of NAC;the expressions of ki-67(OR=0.260,95%CI:0.080～0.849,P=0.026) and ERCC1(OR=0.264,95%CI:0.078～0.899,P=0.033) were independent factors affecting pCR. There was no correlation between ki-67 expression and ERCC1 expression(P>0.05). [Conclusion]In gastric cancer patients,high Ki-67 expression and negative ERCC1 expression are predictive indicators for high pathological response rate after NAC. Meanwhile,it may be helpful for better individualized NAC planning with combined considerations of the status of other related factors.
[Purpose] To investigate the expression level of Ki-67 and ERCC1 in patients with gastric cancer undergoing neoadjuvant chemotherapy(NAC). [Methods] One hundred and twenty-six patients with gastric cancer who underwent radical surgery after NAC were enrolled. The expression level of ki67 and ERCC1 in tumor tissues from the gastroscopy and postoperative specimens were detected with immunohistochemistry. The predictive value of Ki67 and ERCC1 expression for NAC response was analyzed by multivariate Logistic regression and Spearman correlation methods.[Results] The univariate analysis showed that response rate after NAC was significantly related to the T stage,clinical stage,ki-67 expression and ki-67 changes after NAC as well as ERCC1 expression(P<0.05);T staging,ki-67 expression and ERCC1 expression were correlated with pathological complete response(pCR) after NAC in gastric cancer patients(P<0.05). Multivariate analysis revealed that Ki-67(OR=7.956,95%CI:1.305 ～48.492,P=0.025),ki-67 changes after NAC(OR=6.497,95%CI:1.125～37.528,P=0.036) and ERCC1(OR=5.271,95%CI:1.020 ～27.255,P=0.047)expression level were the independent predictive factors for response rate of NAC;the expressions of ki-67(OR=0.260,95%CI:0.080～0.849,P=0.026) and ERCC1(OR=0.264,95%CI:0.078～0.899,P=0.033) were independent factors affecting pCR. There was no correlation between ki-67 expression and ERCC1 expression(P>0.05). [Conclusion]In gastric cancer patients,high Ki-67 expression and negative ERCC1 expression are predictive indicators for high pathological response rate after NAC. Meanwhile,it may be helpful for better individualized NAC planning with combined considerations of the status of other related factors.
引文
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[12]Mo J,Luo M,Cui J,et al.Prognostic value of ERCC1 and ERCC2 gene polymorphisms in patients with gastric cancer receiving platinum-based chemotherapy[J].Int J Clin Exp Pathol,2015,8(11):15065-15071.
[13]Cabreragaleana P,Mu?oz Monta?o W,Laramedina F,et al.Ki67 changes identify worse outcomes in residual breast cancer tumors after neoadjuvant chemotherapy[J].Oncologist,2018,23(6):670-678.
[14]Li T,Liang MX,Feng DF,et al.Correlation between the expression level of ERCC1 and the efficacy of platinumbased neoadjuvant chemotherapy for gastric cancer[J].Journal of Medical Research,2014,43(3):39-42.[李涛,梁美霞,冯道夫,等.ERCC1表达水平与以铂类药物为基础的胃癌新辅助化疗疗效相关性研究[J].医学研究杂志,2014,43(3):39-42.]
[2]Min KW,Kim DH,Son BK,et al.A high Ki67/BCL2 index could predict lower disease-free and overall survival in intestinal-type gastric cancer[J].Eur Surg Res,2017,58(3-4):158-168.
[3]Ko GH,Go SI,Lee WS,et al.Prognostic impact of Ki-67in patients with gastric cancer-the importance of depth of invasion and histologic differentiation[J].Medicine,2017,96(25):e7181.
[4]Badary DM,Abdel-Wanis ME,Hafez MZ,et al.Immunohistochemical analysis of PTEN,HER2/neu,and ki67 expression in patients with gastric cancer and their association with survival[J].Pathophys,2017,24(2):99-103.
[5]Wan J,Chao L,Lee AC,et al.Higher expression of ER-CC1 may be associated with resistance to adjuvant platinum-based chemotherapy in gastric cancer[J].Cancer Invest,2017,35(2):85-91.
[6]Deng Q,Yang H,Lin Y,et al.Prognostic value of ERCC1mRNA expression in non-small cell lung cancer,breast cancer,and gastric cancer in patients from Southern China[J].Int J Clin Exp Pathol,2014,7(12):8312-8321.
[7]Sano T,Aiko T.New Japanese classifications and treatment guidelines for gastric cancer:revision concepts and major revised points[J].Gastric Cancer,2012,14(2):97-100.
[8]Xu W,Beeharry M K,Liu W,et al.Preoperative chemotherapy for gastric cancer:personal interventions and precision medicine[J].Biomed Res Int,2016,6:1-10.
[9]Xiong BH,Cheng Y,Ma L,et al.An updated meta-analysis of randomized controlled trial assessing the effect of neoadjuvant chemotherapy in advanced gastric cancer.[J].Surg Oncol,2014,40(10):1321-1330.
[10]Zhan H,Long B,Wang ZJ,et al.Efficacy and safety of neoadjuvant chemotherapy containing tegafur gimeracil oteracil potassium combined with surgery in the treatment of advanced gastric cancer:a meta-analysis[J].Chinese Journal of Evidence-Based Medicine,2017,7:820-828.[展昊,龙勃,王振江,等.含替吉奥的新辅助化疗联合手术治疗进展期胃癌有效性和安全性的Meta分析[J].中国循证医学杂志,2017,7:820-828.]
[11]Hu SB1,Liu CH1,Wang X,et al.Pathological evaluation of neoadjuvant chemotherapy in advanced gastric cancer[J].World J Surg Oncol,2019,17(1):3-7.
[12]Mo J,Luo M,Cui J,et al.Prognostic value of ERCC1 and ERCC2 gene polymorphisms in patients with gastric cancer receiving platinum-based chemotherapy[J].Int J Clin Exp Pathol,2015,8(11):15065-15071.
[13]Cabreragaleana P,Mu?oz Monta?o W,Laramedina F,et al.Ki67 changes identify worse outcomes in residual breast cancer tumors after neoadjuvant chemotherapy[J].Oncologist,2018,23(6):670-678.
[14]Li T,Liang MX,Feng DF,et al.Correlation between the expression level of ERCC1 and the efficacy of platinumbased neoadjuvant chemotherapy for gastric cancer[J].Journal of Medical Research,2014,43(3):39-42.[李涛,梁美霞,冯道夫,等.ERCC1表达水平与以铂类药物为基础的胃癌新辅助化疗疗效相关性研究[J].医学研究杂志,2014,43(3):39-42.]