A three-gene signature as potential predictive biomarker for irinotecan sensitivity in gastric cancer

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• 作者：Jie Shen (1)
  Jia Wei (1)
  Hao Wang (2)
  Guofeng Yue (3)
  Lixia Yu (1)
  Yang Yang (1)
  Li Xie (1)
  Zhengyun Zou (1)
  Xiaoping Qian (1)
  Yitao Ding (2)
  Wenxian Guan (2)
  Baorui Liu (1)
  
• 关键词：Personalized chemotherapy ; Irinotecan ; Gastric cancer ; HDRA ; Immunodeficient mice
• 刊名：Journal of Translational Medicine
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：11
• 期：1
• 全文大小：537KB
• 参考文献：1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. / CA Cancer J Clin 2011, 61:69-0. CrossRef
  2. Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE: Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. / J Clin Oncol 2006, 24:2903-909. CrossRef
  3. Kubota T: New chemotherapy strategies for gastric cancer. / In Vivo 2008, 22:273-78.
  4. Wesolowski R, Lee C, Kim R: Is there a role for second-line chemotherapy in advanced gastric cancer? / Lancet Oncol 2009, 10:903-12. CrossRef
  5. Farhat FS: A general review of the role of irinotecan (CPT11) in the treatment of gastric cancer. / Med Oncol 2007, 24:137-46. CrossRef
  6. Schilsky RL: Personalized medicine in oncology: the future is now. / Nat Rev Drug Discov 2010, 9:363-66. CrossRef
  7. Wei J, Costa C, Ding Y, Zou Z, Yu L, Sanchez JJ, Qian X, Chen H, Gimenez-Capitan A, Meng F: mRNA expression of BRCA1, PIAS1, and PIAS4 and survival after second-line docetaxel in advanced gastric cancer. / J Natl Cancer Inst 2011, 103:1552-556. CrossRef
  8. Wang L, Wei J, Qian X, Yin H, Zhao Y, Yu L, Wang T, Liu B: ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel. / BMC Cancer 2008, 8:97. CrossRef
  9. Shen J, Wang H, Wei J, Yu L, Xie L, Qian X, Zou Z, Liu B, Guan W: Thymidylate synthase mRNA levels in plasma and tumor as potential predictive biomarkers for raltitrexed sensitivity in gastric cancer. / Int J Cancer 2012, 131:E938-E945. CrossRef
  10. Wang L, Liu B, Wang T, Ding Y, Qian X, Zhao Y: Detection of cell-free ERCC1 and thymidylate synthase (TS) mRNA in malignant effusions and its association with anticancer drug sensitivity. / Anticancer Res 2008, 28:1085-091.
  11. Wei J, Zou Z, Qian X, Ding Y, Xie L, Sanchez JJ, Zhao Y, Feng J, Ling Y, Liu Y: ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen. / Br J Cancer 2008, 98:1398-402. CrossRef
  12. Xu Y, Villalona-Calero MA: Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity. / Ann Oncol 2002, 13:1841-851. CrossRef
  13. Dopeso H, Mateo-Lozano S, Elez E, Landolfi S, Ramos Pascual FJ, Hernandez-Losa J, Mazzolini R, Rodrigues P, Bazzocco S, Carreras MJ: Aprataxin tumor levels predict response of colorectal cancer patients to irinotecan-based treatment. / Clin Cancer Res 2010, 16:2375-382. CrossRef
  14. Braun MS, Richman SD, Quirke P, Daly C, Adlard JW, Elliott F, Barrett JH, Selby P, Meade AM, Stephens RJ: Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. / J Clin Oncol 2008, 26:2690-698. CrossRef
  15. Gilbert DC, Chalmers AJ, El-Khamisy SF: Topoisomerase I inhibition in colorectal cancer: biomarkers and therapeutic targets. / Br J Cancer 2012, 106:18-4. CrossRef
  16. Tessema M, Yingling CM, Thomas CL, Klinge DM, Bernauer AM, Liu Y, Dacic S, Siegfried JM, Dahlberg SE, Schiller JH, Belinsky SA: SULF2 methylation is prognostic for lung cancer survival and increases sensitivity to topoisomerase-I inhibitors via induction of ISG15. / Oncogene 2012, 31:4107-116. CrossRef
  17. Desai SD, Haas AL, Wood LM, Tsai YC, Pestka S, Rubin EH, Saleem A, Nur EKA, Liu LF: Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway. / Cancer Res 2006, 66:921-28. CrossRef
  18. Furukawa T, Kubota T, Hoffman RM: Clinical applications of the histoculture drug response assay. / Clin Cancer Res 1995, 1:305-11.
  19. Fujita Y, Hiramatsu M, Kawai M, Nishimura H, Miyamoto A, Tanigawa N: Histoculture drug response assay predicts the postoperative prognosis of patients with esophageal cancer. / Oncol Rep 2009, 21:499-05.
  20. Margeli M, Cirauqui B, Castella E, Tapia G, Costa C, Gimenez-Capitan A, Barnadas A, Sanchez Ronco M, Benlloch S, Taron M, Rosell R: The prognostic value of BRCA1 mRNA expression levels following neoadjuvant chemotherapy in breast cancer. / PLoS One 2010, 5:e9499. CrossRef
  21. Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(?delta delta C(T)) method. / Methods 2001, 25:402-08. CrossRef
  22. Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, Chen Y, Xu L, Zen K, Zhang C, Shen H: Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. / J Clin Oncol 2010, 28:1721-726. CrossRef
  23. Fichtner I, Rolff J, Soong R, Hoffmann J, Hammer S, Sommer A, Becker M, Merk J: Establishment of patient-derived non-small cell lung cancer xenografts as models for the identification of predictive biomarkers. / Clin Cancer Res 2008, 14:6456-468. CrossRef
  24. Chen HY, Yu SL, Chen CH, Chang GC, Chen CY, Yuan A, Cheng CL, Wang CH, Terng HJ, Kao SF: A five-gene signature and clinical outcome in non-small-cell lung cancer. / N Engl J Med 2007, 356:11-0. CrossRef
  25. Larsen JE, Pavey SJ, Passmore LH, Bowman RV, Hayward NK, Fong KM: Gene expression signature predicts recurrence in lung adenocarcinoma. / Clin Cancer Res 2007, 13:2946-954. CrossRef
  26. Dowsett M, Cuzick J, Wale C, Forbes J, Mallon EA, Salter J, Quinn E, Dunbier A, Baum M, Buzdar A: Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. / J Clin Oncol 2010, 28:1829-834. CrossRef
  27. Tanino H, Oura S, Hoffman RM, Kubota T, Furukawa T, Arimoto J, Yoshimasu T, Hirai I, Bessho T, Suzuma T: Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay. / Anticancer Res 2001, 21:4083-086.
  28. Ariyoshi Y, Shimahara M, Tanigawa N: Study on chemosensitivity of oral squamous cell carcinomas by histoculture drug response assay. / Oral Oncol 2003, 39:701-07. CrossRef
  29. Hasegawa Y, Goto M, Hanai N, Ijichi K, Adachi M, Terada A, Hyodo I, Ogawa T, Furukawa T: Evaluation of optimal drug concentration in histoculture drug response assay in association with clinical efficacy for head and neck cancer. / Oral Oncol 2007, 43:749-56. CrossRef
  30. Sausville EA, Burger AM: Contributions of human tumor xenografts to anticancer drug development. / Cancer Res 2006, 66:3351-354. discussion 3354 CrossRef
  31. Talmadge JE, Singh RK, Fidler IJ, Raz A: Murine models to evaluate novel and conventional therapeutic strategies for cancer. / Am J Pathol 2007, 170:793-04. CrossRef
  32. Villarroel MC, Rajeshkumar NV, Garrido-Laguna I, De Jesus-Acosta A, Jones S, Maitra A, Hruban RH, Eshleman JR, Klein A, Laheru D: Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. / Mol Cancer Ther 2011, 10:3-. CrossRef
  33. Hidalgo M, Bruckheimer E, Rajeshkumar NV, Garrido-Laguna I, De Oliveira E, Rubio-Viqueira B, Strawn S, Wick MJ, Martell J, Sidransky D: A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer. / Mol Cancer Ther 2011, 10:1311-316. CrossRef
  34. Ramaswamy S: Translating cancer genomics into clinical oncology. / N Engl J Med 2004, 350:1814-816. CrossRef
  35. Mariadason JM, Arango D, Shi Q, Wilson AJ, Corner GA, Nicholas C, Aranes MJ, Lesser M, Schwartz EL, Augenlicht LH: Gene expression profiling-based prediction of response of colon carcinoma cells to 5-fluorouracil and camptothecin. / Cancer Res 2003, 63:8791-812.
  36. Zander SA, Kersbergen A, van der Burg E, de Water N, van Tellingen O, Gunnarsdottir S, Jaspers JE, Pajic M, Nygren AO, Jonkers J: Sensitivity and acquired resistance of BRCA1;p53-deficient mouse mammary tumors to the topoisomerase I inhibitor topotecan. / Cancer Res 2010, 70:1700-710. CrossRef
  37. Kirschner K, Melton DW: Multiple roles of the ERCC1-XPF endonuclease in DNA repair and resistance to anticancer drugs. / Anticancer Res 2010, 30:3223-232.
  38. Tessema M, Yu YY, Stidley CA, Machida EO, Schuebel KE, Baylin SB, Belinsky SA: Concomitant promoter methylation of multiple genes in lung adenocarcinomas from current, former and never smokers. / Carcinogenesis 2009, 30:1132-138. CrossRef
  
• 作者单位：Jie Shen (1)
  Jia Wei (1)
  Hao Wang (2)
  Guofeng Yue (3)
  Lixia Yu (1)
  Yang Yang (1)
  Li Xie (1)
  Zhengyun Zou (1)
  Xiaoping Qian (1)
  Yitao Ding (2)
  Wenxian Guan (2)
  Baorui Liu (1)
  
  1. The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, 321 Zhongshan Rd, Nanjing, 210008, China
  2. Department of General Surgery, Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, 321 Zhongshan Rd, Nanjing, 210008, China
  3. Nanjing University of Traditional Chinese Medicine, 138 Xianlin Rd, Nanjing, 210029, China
  

文摘

Objective Personalized chemotherapy based on molecular biomarkers can maximize anticancer efficiency. We aim to investigate predictive biomarkers capable of predicting response to irinotecan-based treatment in gastric cancer. Methods We examined gene expression of APTX, BRCA1, ERCC1, ISG15, Topo1 and methylation of SULF2 in formalin-fixed paraffin-embedded gastric cancer tissues from 175 patients and evaluated the association between gene expression levels or methylation status and in vitro sensitivity to irinotecan. We used multiple linear regression analysis to develop a gene-expression model to predict irinotecan sensitivity in gastric cancer and validated this model in vitro and vivo. Results Gene expression levels of APTX, BRCA1 and ERCC1 were significantly lower in irinotecan-sensitive gastric cancer samples than those irinotecan-resistant samples (P < 0.001 for all genes), while ISG15 (P = 0.047) and Topo1 (P = 0.002) were significantly higher. Based on those genes, a three-gene signature were established, which was calculated as follows: Index =0.488 - 0.020× expression level of APTX + 0.015× expression level of Topo1 - 0.011 × expression level of BRCA1. The three-gene signature was significantly associated with irinotecan sensitivity (rho = 0.71, P < 0.001). The sensitivity and specificity for the prediction of irinotecan sensitivity based on the three-gene signature reached 73% and 86%, respectively. In another independent testing set, the irinotecan inhibition rates in gastric samples with sensitive-signature were much higher than those with resistant-signature (65% vs. 22%, P < 0.001). Irinotecan therapy with 20 mg/kg per week to immunodeficient mice carrying xenografts with sensitive-signature dramatically arrested the growth of tumors (P < 0.001), but had no effect on mice carrying xenografts with resistant-signature. Conclusions The three-gene signature established herein is a potential predictive biomarker for irinotecan sensitivity in gastric cancer.