ERCC1在结直肠癌组织中的表达及预后价值
|
摘要
目的:探究核苷酸切除修复交叉互补基因1(excision repair cross-complementation gene 1,ERCC1)表达对结直肠癌(colorectal cancer,CRC)患者铂类辅助化疗的预后价值。方法:选取2011年01月至2013年01月安徽医科大学附属六安医院行CRC根治术后接受m FOLFOX6方案化疗的患者共84例,通过免疫组化方法评估ERCC1在CRC组织中表达情况,分析ERCC1表达与预后的关联。结果:ERCC1高表达30例(35. 7%)。Kaplan-Meier曲线显示ERCC1高表达的CRC患者无病生存期(DFS)和总生存期(OS)均缩短(P均<0. 001)。多因素COX分析显示ERCC1高表达(DFS HR=4. 645,95%CI:2. 045～10. 548,P <0. 001; OS HR=4. 898,95%CI:1. 971～12. 170,P <0. 001)是CRC患者预后的不良因素,分析各亚组患者中ERCC1表达与生存相关性得到相似的结果。复发患者中ERCC1高表达的肝肺转移占68. 8%(11/16),低表达的腹腔转移为70. 0%(7/10),ERCC1表达与首次复发模式显著相关(P=0. 006)。结论:ERCC1表达可作为评价CRC患者预后的重要指标。ERCC1表达可能有助于预测CRC患者辅助化疗后首次复发模式。ERCC1表达的预后价值需进一步研究。
Objective: To explore the prognostic value of nucleotide excision repair cross-complementation gene 1( ERCC1) expression in patients receiving oxaliplatin adjuvant chemotherapy with colorectal cancer( CRC). Methods: A total of 84 patients undergoing m FOLFOX6 chemotherapy after radical resection of CRC from Lu'an Hospital Affiliated to Anhui Medical University from January 2011 to January 2013 were selected. The expression of ERCC1 in CRC tissues was evaluated by immunohistochemistry and the correlation between ERCC1 expression and prognosis was analyzed. Results: ERCC1 was highly expressed in 30 patients( 35. 7%). Kaplan-Meier curves showed a reduction in disease-free survival( DFS) and overall survival( OS) in CRC patients with high ERCC1 expression( P < 0. 001). Multivariate COX analysis showed that high expression of ERCC1( DFS HR = 4. 645,95% CI: 2. 045 ～10. 548,P < 0. 001. OS HR = 4. 898,95% CI: 1. 971 ～ 12. 170,P < 0. 001) was a poor prognostic factor. Analysis of the correlation between ERCC1 expression and survival in similar subgroups was similar. Among the 16 patients with high expression and recurrence of ERCC1,liver and lung metastasis was 68. 8%( 11/16). In 10 patients with low expression of ERCC1 and recurrence,70. 0%( 7/10) of the patients had peritoneal metastasis. ERCC1 expression was significantly associated with the first recurrence pattern( P = 0. 006). Conclusion: ERCC1 expression can be used as an important indicator to evaluate the prognosis of CRC patients and may help predict the first relapse pattern after adjuvant chemotherapy in CRC patients. The prognostic value of ERCC1 expression needs further study.
Objective: To explore the prognostic value of nucleotide excision repair cross-complementation gene 1( ERCC1) expression in patients receiving oxaliplatin adjuvant chemotherapy with colorectal cancer( CRC). Methods: A total of 84 patients undergoing m FOLFOX6 chemotherapy after radical resection of CRC from Lu'an Hospital Affiliated to Anhui Medical University from January 2011 to January 2013 were selected. The expression of ERCC1 in CRC tissues was evaluated by immunohistochemistry and the correlation between ERCC1 expression and prognosis was analyzed. Results: ERCC1 was highly expressed in 30 patients( 35. 7%). Kaplan-Meier curves showed a reduction in disease-free survival( DFS) and overall survival( OS) in CRC patients with high ERCC1 expression( P < 0. 001). Multivariate COX analysis showed that high expression of ERCC1( DFS HR = 4. 645,95% CI: 2. 045 ～10. 548,P < 0. 001. OS HR = 4. 898,95% CI: 1. 971 ～ 12. 170,P < 0. 001) was a poor prognostic factor. Analysis of the correlation between ERCC1 expression and survival in similar subgroups was similar. Among the 16 patients with high expression and recurrence of ERCC1,liver and lung metastasis was 68. 8%( 11/16). In 10 patients with low expression of ERCC1 and recurrence,70. 0%( 7/10) of the patients had peritoneal metastasis. ERCC1 expression was significantly associated with the first recurrence pattern( P = 0. 006). Conclusion: ERCC1 expression can be used as an important indicator to evaluate the prognosis of CRC patients and may help predict the first relapse pattern after adjuvant chemotherapy in CRC patients. The prognostic value of ERCC1 expression needs further study.
引文
[1]Siegel R,Ma J,Zou Z,et al.Cancer statistics,2014[J].CA Cancer Clin,2014,64(1):9-29.
[2]Amira B Kassem,Salem Eid Salem,Mohamed E Abdelrahim,et al.ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt[J].Experimental and Molecular Pathology,2017,102(1):78-85.
[3]Yang H,Li G,Li WF.Association between ERCC1 and XPF polymorphisms and risk of colorectal cancer[J].Genet Mol Res,2015,14(1):700-705.
[4]Smith DH,Fiehn AM,Fogh L,et al.Measuring ERCC1 protein expression in cancer specimens:Validation of a novel antibody[J].Sci Rep,2014,7(4):4313.
[5]Van Huis-Tanja LH,Kweekel DM,Lu X,et al.Excision repair crosscomplementation group 1(ERCC1)C118T SNP does not affect cellular response to oxaliplatin[J].Mutat Res,2014,759:37-44.
[6]Lord RV,Brabender J,Gandara D,et al.Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer[J].Clin Cancer Res,2002,8(7):2286-2291.
[7]Bellmunt J,Paz-Ares L,Cuello M,et al.Gene expression of ER-CC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy[J].Ann Oncol,2007,18(3):522-528.
[8]Kwon HC,Roh MS,Oh SY,et al.Prognostic value of expression of ERCC1,thymidylate synthase,and glutathione S-transferase P1 for5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer[J].Ann Oncol,2007,18(3):504-509.
[9]Li MX,Bi XY,Zhao H,et al.Excision repair cross-complementation group 1 is a prognostic biomarker in patients with colorectal cancer receiving chemotherapy[J].Chin Med J(Engl),2016,129(5):586-593.
[10]Li S,Zhu L,Yao L,et al.Association between ERCC1 and TSmRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil(5-FU)adjuvant chemotherapy[J].BMC Gastroenterol,2014,14:154-161.
[11]Lenz HJ,Lee FC,Yau L,et al.MAVERICC,a phase 2 study of m FOLFOX6-bevacizumab(BV)vs FOLFIRI-BV with biomarker stratification as first-line(1 L)chemotherapy(CT)in patients(pts)with metastatic colorectal cancer(m CRC)[J].ASCOAnnual Meeting Proceedings,2016,34:493.
[12]Li P,Fang YJ,Li F,et al.ERCC1,defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy[J].Br J Cancer,2013,108(6):1238-1244.
[13]Kelly H,Goldberg RM.Systemic therapy for metastatic colorectal cancer:Current options,current evidence[J].J Clin Oncol,2005,23:4553-4560.
[14]Huang MY,Tsai HL,Lin CH,et al.Predictive value of ERCC1,ERCC2,and XRCC1 overexpression for stage III colorectal cancer patients receiving FOLFOX-4 adjuvant chemotherapy[J].J Surg Oncol,2013,108(7):457-464.
[15]Zhang Y,Ma J,Zhang S,et al.A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites[J].Int J Colorectal Dis,2015,30(9):1173-1183.
[16]Patel M,Mc Sorley ST,Park JH,et al.The relationship between right-sided tumour location,tumour microenvironment,systemic inflammation,adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer[J].Br J Cancer,2018,118(5):705-712.
[17]Kornmann M,Staib L,Wiegel T,et al.Long-term results of 2 adjuvant trials reveal differences in chemosensitivity and the pattern of metastases between colon cancer and rectal cancer[J].Clin Colorectal Cancer,2013,12(1):54-61.
[18]Liang J,Jiang T,Yao RY,et al.The combination of ERCC1 and XRCC1 gene polymorphisms better predicts clinical outcome to oxaliplatin-based chemotherapy in metastatic colorectal cancer[J].Cancer Chemother Pharmacol,2010,66(3):493-500.
[19]Chiang JM,Hsieh PS,Chen JS,et al.Rectal cancer level significantly affects rates and patterns of distant metastases among rectal cancer patients post curative-intent surgery without neoadjuvant therapy[J].World J Surg Oncol,2014,12:197.
[20]Gao Y,Wang J,Zhou Y,et al.Evaluation of serum CEA,CA19-9,CA72-4,CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer[J].Sci Rep,2018,8(1):2732.
[2]Amira B Kassem,Salem Eid Salem,Mohamed E Abdelrahim,et al.ERCC1 and ERCC2 as predictive biomarkers to oxaliplatin-based chemotherapy in colorectal cancer patients from Egypt[J].Experimental and Molecular Pathology,2017,102(1):78-85.
[3]Yang H,Li G,Li WF.Association between ERCC1 and XPF polymorphisms and risk of colorectal cancer[J].Genet Mol Res,2015,14(1):700-705.
[4]Smith DH,Fiehn AM,Fogh L,et al.Measuring ERCC1 protein expression in cancer specimens:Validation of a novel antibody[J].Sci Rep,2014,7(4):4313.
[5]Van Huis-Tanja LH,Kweekel DM,Lu X,et al.Excision repair crosscomplementation group 1(ERCC1)C118T SNP does not affect cellular response to oxaliplatin[J].Mutat Res,2014,759:37-44.
[6]Lord RV,Brabender J,Gandara D,et al.Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer[J].Clin Cancer Res,2002,8(7):2286-2291.
[7]Bellmunt J,Paz-Ares L,Cuello M,et al.Gene expression of ER-CC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy[J].Ann Oncol,2007,18(3):522-528.
[8]Kwon HC,Roh MS,Oh SY,et al.Prognostic value of expression of ERCC1,thymidylate synthase,and glutathione S-transferase P1 for5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer[J].Ann Oncol,2007,18(3):504-509.
[9]Li MX,Bi XY,Zhao H,et al.Excision repair cross-complementation group 1 is a prognostic biomarker in patients with colorectal cancer receiving chemotherapy[J].Chin Med J(Engl),2016,129(5):586-593.
[10]Li S,Zhu L,Yao L,et al.Association between ERCC1 and TSmRNA levels and disease free survival in colorectal cancer patients receiving oxaliplatin and fluorouracil(5-FU)adjuvant chemotherapy[J].BMC Gastroenterol,2014,14:154-161.
[11]Lenz HJ,Lee FC,Yau L,et al.MAVERICC,a phase 2 study of m FOLFOX6-bevacizumab(BV)vs FOLFIRI-BV with biomarker stratification as first-line(1 L)chemotherapy(CT)in patients(pts)with metastatic colorectal cancer(m CRC)[J].ASCOAnnual Meeting Proceedings,2016,34:493.
[12]Li P,Fang YJ,Li F,et al.ERCC1,defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy[J].Br J Cancer,2013,108(6):1238-1244.
[13]Kelly H,Goldberg RM.Systemic therapy for metastatic colorectal cancer:Current options,current evidence[J].J Clin Oncol,2005,23:4553-4560.
[14]Huang MY,Tsai HL,Lin CH,et al.Predictive value of ERCC1,ERCC2,and XRCC1 overexpression for stage III colorectal cancer patients receiving FOLFOX-4 adjuvant chemotherapy[J].J Surg Oncol,2013,108(7):457-464.
[15]Zhang Y,Ma J,Zhang S,et al.A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites[J].Int J Colorectal Dis,2015,30(9):1173-1183.
[16]Patel M,Mc Sorley ST,Park JH,et al.The relationship between right-sided tumour location,tumour microenvironment,systemic inflammation,adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer[J].Br J Cancer,2018,118(5):705-712.
[17]Kornmann M,Staib L,Wiegel T,et al.Long-term results of 2 adjuvant trials reveal differences in chemosensitivity and the pattern of metastases between colon cancer and rectal cancer[J].Clin Colorectal Cancer,2013,12(1):54-61.
[18]Liang J,Jiang T,Yao RY,et al.The combination of ERCC1 and XRCC1 gene polymorphisms better predicts clinical outcome to oxaliplatin-based chemotherapy in metastatic colorectal cancer[J].Cancer Chemother Pharmacol,2010,66(3):493-500.
[19]Chiang JM,Hsieh PS,Chen JS,et al.Rectal cancer level significantly affects rates and patterns of distant metastases among rectal cancer patients post curative-intent surgery without neoadjuvant therapy[J].World J Surg Oncol,2014,12:197.
[20]Gao Y,Wang J,Zhou Y,et al.Evaluation of serum CEA,CA19-9,CA72-4,CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer[J].Sci Rep,2018,8(1):2732.