• 川北醫(yī)學(xué)院第二臨床醫(yī)學(xué)院　南充市中心醫(yī)院腫瘤中心（四川南充，637000）;

【摘要】　目的　 剪切修復(fù)偶聯(lián)因子1（ERCC1）是核苷酸外切修復(fù)家族中的重要成員，它在核酸損傷修復(fù)過程和凋亡過程中起著重要作用；存活蛋白（Survivin）屬凋亡抑制蛋白家族，是迄今發(fā)現(xiàn)的最強(qiáng)的凋亡抑制因子之一。研究中初步探索晚期非小細(xì)胞肺癌（non-small-cell lung cancer，NSCLC）中ERCC1和Survivin與鉑類化學(xué)療法敏感性的關(guān)系及其相關(guān)性。　方法　 2001年1月－2002年6月對(duì)51例晚期NSCLC（ⅢB或Ⅳ期）標(biāo)本經(jīng)免疫組織化學(xué)檢測(cè)ERCC1和Survivin的表達(dá)，患者行至少2周期含鉑方案化學(xué)療法，2周期化學(xué)療法后評(píng)價(jià)療效，采用SPSS 13.0軟件就檢測(cè)指標(biāo)和化學(xué)療法療效評(píng)價(jià)進(jìn)行相關(guān)統(tǒng)計(jì)分析。　結(jié)果　 ERCC1和Survivin在腫瘤組織中陽性表達(dá)率分別為58.8 %（30/51）和76.5 %（39/51）。ERCC1陰性組化學(xué)療法有效率高于陽性組（P lt;0.05），5年生存時(shí)間高于陽性組（P lt;0.05）；Survivin陰性組化學(xué)療法有效率雖高于陽性組，但無統(tǒng)計(jì)學(xué)意義（P gt;0.05），其5年生存時(shí)間與陰性組比較無差別（P gt;0.05）。Spearman相關(guān)分析提示ERCC1與Survivin之間無相關(guān)性（rs=-0.088，P=0.537）。　結(jié)論　 ERCC1和Survivin可能與NSCLC的發(fā)生相關(guān)，ERCC1可能與腫瘤的預(yù)后相關(guān)，并對(duì)化學(xué)療法療效具有一定預(yù)測(cè)價(jià)值。ERCC1和Survivin之間耐藥機(jī)制可能各不相同。
【Abstract】　Objective　 Excision repair cross-complementing 1 (ERCC1), an important member of the DNA repair gene family, plays a key role in nucleotide excision repair and apoptosis of tumor cells. Survivin, a member of inhibitor of apoptosis protein (IAP) family, is one of the most powerful factors in inhibiting apoptosis up to now. This study is to explore the value of ERCC1 and Survivin in predicting the sensitivity of non-small cell lung cancer (NSCLC) to platinum-based chemotherapy and the interrelationship between the two markers.　Methods　 From January 2001 to June 2002, expressions of ERCC1 and Survivin of 51 advanced NSCLC patients (Ⅲ B or IV) were tested through immunohistochemistry. The patients were treated with at least 2 cycles of platinum-based chemotherapy. The curative effect was evaluated later, and the relationship among detected data, curative effect of chemotherapy and patients′ clinical parameters were analyzed with SPSS 13.0 software.　Results　 The positive expression rates of ERCC1 and Survivin in NSCLC tissues were 58.8 % (30/51) and 76.5 % (39/51), respectively. The effective rate of chemotherapy and 5-year survival rate for the negative group of ERCC1 were significantly higher than those for the positive group (P lt;0.05). The results for Survivin were similar to those for ERCC1, but there was no statistical significance (P gt;0.05). We also found there was no relationship between ERCC1 and Survivin by Spearman′s correlation analysis (rs=-0.088, P=0.537).　Conclusion　 ERCC1 and Survivin may be correlated with the development of NSCLC, and ERCC1 may be related to curative effect and prognosis of NSCLC. There was probably no mechanism of coordination or regulation in multi-drug resistance between ERCC1 and Survivin.

引用本文： 何朗,郭翠華,別俊,付曦,李光明. 剪切修復(fù)偶聯(lián)因子1和存活蛋白對(duì)非小細(xì)胞肺癌. 華西醫(yī)學(xué), 2011, 26(7): 1059-1062. doi: 復(fù)制

1. 　Kosmidis P. Chemotherapy in NSCLC: historical review [J]. Lung Cancer, 2002, 38 (Suppl 3): 19-22.
2. 　Fong K, Sekido Y, Gazdar JD, et al. Lung cancer 9: Molecular biology of lung cancer clinical implications[J].Thorax, 2003, 58 (10): 892-900.
3. 　Wachters FM, Wong LS, Timens W, et al. ERCC1,hRad51,and BRCA1 protein expression in relation to tumour response and survival of stage Ⅲ/Ⅳ NSCLC patients treated with chemotherapy[J]. Lung Cancer, 2005, 50(2): 211-219.
4. 　Tanaka K, Iwamoto S, Gon G, et al.Expression of survivin and its relationship to loss of apoptosis in breast carcinomas[J]. Clin Cancer Res, 2000, 6(1): 127-134.
5. 　Saeb? M, Skjelbred CF, Nex? BA, et al. Increased mRNA expression levels of ERCC1,OGG1 and RAI in colorectal adenomas and carcinomas[J].BMC Cancer, 2006, 16(6): 208.
6. 　Azuma K, Komohara Y, Sasada T, et al. Excision repair cross-complementation group 1 predicts progression-free and overall survival in non-small cell lung cancer patients treated with platinum-based chemotherapy[J]. Cancer Sci, 2007, 98(9): 1336-1343.
7. 　Ikehara M, Oshita F, Kameda Y, et al. Expression of surviving correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung[J]. Oncol Rep, 2002, 9(4): 835-838.
8. 　Li F, Yang J, Ramnath N, et al. Nuclear or cytoplasmic expression of survivin:what is the significance?[J]. Int J Cancer, 2005, 114(4): 509-512.
9. 　Akyürek N, Memi? L, Ekinci Ö, et al. Survivin expression in pre-invasive lesions and non-small cell lung carcinoma[J]. Virchows Arch, 2006, 449(2): 164-170.〖ZK)〗.
10. 　Douillard JY, Rosell R, de Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage ⅠB-ⅢA non-small-cell lung cancer(Adjuvant Navelbine International Trialist Association[ANITA]):a randomized controlled trial[J]. Lancet Oncol, 2006, 7(9): 719-727.
11. 　Anonymous. Chemotherapy in non-small-cell lung cancer:A meta-analysis using updated data on individual patients from 52 randomized trials.Non-small cell lung cancer collaborative Group[J]. BMJ, 1995, 311(7010): 899-909.
12. 　Garcia-Campelo R, Alonso-Curbera G, Antón Aparicio LM, et al. Pharmacogenomics in lung cancer: an analysis of DNA repair gene expression in patients treated with platinum-based chemotherapy[J]. Expert Opin Pharmacother, 2005, 6(12): 2015-2026.
13. 　Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy[see comment] [J]. N Engl J Med, 2006, 355(10): 983-991.
14. 　Ho TF, Peng YT, Chuang SM, et al. Prodigiosin down-regulates survivin to facilitate paclitaxel sensitization in human breast carcinoma cell lines [J].Toxicol Appl Pharmacol, 2009, 235(2): 253-260.
15. 　Fareed KR, Al-Attar A, Soomro IN, et al. Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy [J]. Br J Cancer, 2010, 102(11): 1600-1607.
16. 　Wang J, Huang C, Wei XY, et al. Changes of activated circulating endothelial cells and survivin in patients with non-small cell lung cancer after antiangiogenesis therapy[J]. Chin Med J (Engl), 2008, 121(22): 2234-2240.
17. 　Kwon HC, Roh MS, Oh SY, et al. Prognostic value of expression of ERCC1,thymidylate synthase,and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer[J]. Ann Oncol, 2007, 18(3): 504-509.
18. 　Darcy KM, Tian C, Reed E. A Gynecologic Oncology Group Study of Platinum-DNA Adducts and Excision Repair Cross-Complementation Group 1 Expression in Optimal,Stage Ⅲ Epithelial Ovarian Cancer Treated with Platinum-Taxane Chemotherapy[J]. Cancer Res, 2007, 67(9): 4474-4481.
19. 　Deng H, Wu RL, Zhou HY, et al. Significance of Survivin and PTEN expression in full lymph nodeexamined gasTric cancer[J]. World J GasTroenTerol, 2006, 12(7): 1013-1017.
  1. 1. 　Kosmidis P. Chemotherapy in NSCLC: historical review [J]. Lung Cancer, 2002, 38 (Suppl 3): 19-22.
  2. 2. 　Fong K, Sekido Y, Gazdar JD, et al. Lung cancer 9: Molecular biology of lung cancer clinical implications[J].Thorax, 2003, 58 (10): 892-900.
  3. 3. 　Wachters FM, Wong LS, Timens W, et al. ERCC1,hRad51,and BRCA1 protein expression in relation to tumour response and survival of stage Ⅲ/Ⅳ NSCLC patients treated with chemotherapy[J]. Lung Cancer, 2005, 50(2): 211-219.
  4. 4. 　Tanaka K, Iwamoto S, Gon G, et al.Expression of survivin and its relationship to loss of apoptosis in breast carcinomas[J]. Clin Cancer Res, 2000, 6(1): 127-134.
  5. 5. 　Saeb? M, Skjelbred CF, Nex? BA, et al. Increased mRNA expression levels of ERCC1,OGG1 and RAI in colorectal adenomas and carcinomas[J].BMC Cancer, 2006, 16(6): 208.
  6. 6. 　Azuma K, Komohara Y, Sasada T, et al. Excision repair cross-complementation group 1 predicts progression-free and overall survival in non-small cell lung cancer patients treated with platinum-based chemotherapy[J]. Cancer Sci, 2007, 98(9): 1336-1343.
  7. 7. 　Ikehara M, Oshita F, Kameda Y, et al. Expression of surviving correlated with vessel invasion is a marker of poor prognosis in small adenocarcinoma of the lung[J]. Oncol Rep, 2002, 9(4): 835-838.
  8. 8. 　Li F, Yang J, Ramnath N, et al. Nuclear or cytoplasmic expression of survivin:what is the significance?[J]. Int J Cancer, 2005, 114(4): 509-512.
  9. 9. 　Akyürek N, Memi? L, Ekinci Ö, et al. Survivin expression in pre-invasive lesions and non-small cell lung carcinoma[J]. Virchows Arch, 2006, 449(2): 164-170.〖ZK)〗.
  10. 10. 　Douillard JY, Rosell R, de Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage ⅠB-ⅢA non-small-cell lung cancer(Adjuvant Navelbine International Trialist Association[ANITA]):a randomized controlled trial[J]. Lancet Oncol, 2006, 7(9): 719-727.
  11. 11. 　Anonymous. Chemotherapy in non-small-cell lung cancer:A meta-analysis using updated data on individual patients from 52 randomized trials.Non-small cell lung cancer collaborative Group[J]. BMJ, 1995, 311(7010): 899-909.
  12. 12. 　Garcia-Campelo R, Alonso-Curbera G, Antón Aparicio LM, et al. Pharmacogenomics in lung cancer: an analysis of DNA repair gene expression in patients treated with platinum-based chemotherapy[J]. Expert Opin Pharmacother, 2005, 6(12): 2015-2026.
  13. 13. 　Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy[see comment] [J]. N Engl J Med, 2006, 355(10): 983-991.
  14. 14. 　Ho TF, Peng YT, Chuang SM, et al. Prodigiosin down-regulates survivin to facilitate paclitaxel sensitization in human breast carcinoma cell lines [J].Toxicol Appl Pharmacol, 2009, 235(2): 253-260.
  15. 15. 　Fareed KR, Al-Attar A, Soomro IN, et al. Tumour regression and ERCC1 nuclear protein expression predict clinical outcome in patients with gastro-oesophageal cancer treated with neoadjuvant chemotherapy [J]. Br J Cancer, 2010, 102(11): 1600-1607.
  16. 16. 　Wang J, Huang C, Wei XY, et al. Changes of activated circulating endothelial cells and survivin in patients with non-small cell lung cancer after antiangiogenesis therapy[J]. Chin Med J (Engl), 2008, 121(22): 2234-2240.
  17. 17. 　Kwon HC, Roh MS, Oh SY, et al. Prognostic value of expression of ERCC1,thymidylate synthase,and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer[J]. Ann Oncol, 2007, 18(3): 504-509.
  18. 18. 　Darcy KM, Tian C, Reed E. A Gynecologic Oncology Group Study of Platinum-DNA Adducts and Excision Repair Cross-Complementation Group 1 Expression in Optimal,Stage Ⅲ Epithelial Ovarian Cancer Treated with Platinum-Taxane Chemotherapy[J]. Cancer Res, 2007, 67(9): 4474-4481.
  19. 19. 　Deng H, Wu RL, Zhou HY, et al. Significance of Survivin and PTEN expression in full lymph nodeexamined gasTric cancer[J]. World J GasTroenTerol, 2006, 12(7): 1013-1017.