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Predictive and Prognostic Roles of Ribonucleotide Reductase M1 in Patients with Pancreatic Cancer Treated with Gemcitabine: A Meta-analysis

  • Zhang, Xiong (Department of Laboratory Medicine, Hubei Wuchang Hospital) ;
  • Jin, Fen-Shu (Department of Laboratory Medicine, Hubei Wuchang Hospital) ;
  • Zhang, Li-Guo (Department of Laboratory Medicine, Hubei Wuchang Hospital) ;
  • Chen, Rui-Xue (Department of Laboratory Medicine, Hubei Wuchang Hospital) ;
  • Zhao, Jin-Hui (Department of Laboratory Medicine, Hubei Wuchang Hospital) ;
  • Wang, Yan-Nan (Department of Laboratory Medicine, Hubei Wuchang Hospital) ;
  • Wang, En-Fu (Department of Laboratory Medicine, Hubei Wuchang Hospital) ;
  • Jiang, Zhen-Dong (Department of Laboratory Medicine, Hubei Wuchang Hospital)
  • Published : 2013.07.30

Abstract

Increasing scientific evidence suggests that ribonucleotide reductase M1 (RRM1) may be a powerful predictor of survival in patients with pancreatic cancer treated with adjuvant gemcitabine-based chemotherapy after operative resection, but many existing studies have yielded inconclusive results. This meta-analysis aimed to assess the prognostic role of RRM1 in predicting survival in patients with pancreatic cancer treated with gemcitabine. An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through May 1st, 2013. This meta-analysis was performed using the STATA 12.0 software and crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Eight clinical studies were included in this meta-analysis with a total of 665 pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy, including 373 patients in the high RRM1 expression group and 292 patients in the low RRM1 expression group. Our meta-analysis revealed that high RRM1 expression was associated with improved overall survival (OS) of pancreatic cancer patients (HR=1.56, 95%CI=0.95-2.17, P<0.001). High RRM1 expression also was linked to longer disease-free survival (DFS) than low RRM1 expression (HR=1.37, 95%CI=0.25-2.48, P=0.016). In conclusion, our meta-analysis suggests that high RRM1 expression may be associated with improved OS and DFS of pancreatic cancer patients treated with adjuvant gemcitabine-based chemotherapy. Detection of RRM1 expression may be a promising biomarker for gemcitabine response and prognosis in pancreatic cancer patients.

Keywords

Pancreatic cancer;gemcitabine;ribonucleotide reductase M1;meta-analysis

References

  1. Akita H, Zheng Z, Takeda Y, et al (2009). Significance of RRM1 and ERCC1 expression in resectable pancreatic adenocarcinoma. Oncogene, 28, 2903-9. https://doi.org/10.1038/onc.2009.158
  2. Bepler G, Kusmartseva I, Sharma S, et al (2006). RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol, 24, 4731-7. https://doi.org/10.1200/JCO.2006.06.1101
  3. Biggerstaff BJ, Jackson D (2008). The exact distribution of Cochran's heterogeneity statistic in one-way random effects meta-analysis. Stat Med, 27, 6093-110. https://doi.org/10.1002/sim.3428
  4. Choi M, Kim R, Saif MW (2012). What options are available for refractory pancreatic cancer? JOP, 13, 163-5.
  5. Fujita H, Ohuchida K, Mizumoto K, et al (2010). Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy. Neoplasia, 12, 807-17.
  6. Giovannetti E, Mey V, Nannizzi S, et al (2006). Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer. Mol Cancer Ther, 5, 1387-95. https://doi.org/10.1158/1535-7163.MCT-06-0004
  7. Hsu CC, Herman JM, Corsini MM, et al (2010). Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Ann Surg Oncol, 17, 981-90. https://doi.org/10.1245/s10434-009-0743-7
  8. Jackson D, White IR, Riley RD (2012). Quantifying the impact of between-study heterogeneity in multivariate meta-analyses. Stat Med, 31, 3805-20. https://doi.org/10.1002/sim.5453
  9. Jordheim LP, Seve P, Tredan O, et al (2011). The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer. Lancet Oncol, 12, 693-702. https://doi.org/10.1016/S1470-2045(10)70244-8
  10. Kanai M, Yoshimura K, Asada M, et al (2011). A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol, 68, 157-64. https://doi.org/10.1007/s00280-010-1470-2
  11. Kim R, Tan A, Lai KK, et al (2011a). Prognostic roles of human equilibrative transporter 1 (hENT-1) and ribonucleoside reductase subunit M1 (RRM1) in resected pancreatic cancer. Cancer, 117, 3126-34. https://doi.org/10.1002/cncr.25883
  12. Kim ST, Lim do H, Jang KT, et al (2011b). Impact of KRAS mutations on clinical outcomes in pancreatic cancer patients treated with first-line gemcitabine-based chemotherapy. Mol Cancer Ther, 10, 1993-9. https://doi.org/10.1158/1535-7163.MCT-11-0269
  13. Kovacevic Z, Chikhani S, Lovejoy DB, et al (2011). Novel thiosemicarbazone iron chelators induce up-regulation and phosphorylation of the metastasis suppressor N-myc downstream regulated gene 1: a new strategy for the treatment of pancreatic cancer. Mol Pharmacol, 80, 598-609. https://doi.org/10.1124/mol.111.073627
  14. Kwon WS, Rha SY, Choi YH, et al (2006). Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines. Pharmacogenet Genomics, 16, 429-38. https://doi.org/10.1097/01.fpc.0000204999.29924.da
  15. Lai R, Bartlett NL, Mackey JR, et al (2008). High expression of nucleoside transporter protein hENT1 in Reed-Sternberg cells is associated with treatment failure in relapsed/refractory Hodgkin lymphoma patients treated with gemcitabine, vinorelbine and liposomal doxorubicin - a CALGB 59804 correlative study. Leuk Lymphoma, 49, 1202-5. https://doi.org/10.1080/10428190802094237
  16. Lau MK, Davila JA, Shaib YH (2010). Incidence and survival of pancreatic head and body and tail cancers: a population-based study in the United States. Pancreas, 39, 458-62. https://doi.org/10.1097/MPA.0b013e3181bd6489
  17. Li D, Xie K, Wolff R, et al (2004). Pancreatic cancer. Lancet, 363, 1049-57. https://doi.org/10.1016/S0140-6736(04)15841-8
  18. Marechal R, Bachet JB, Mackey JR, et al (2012). Levels of gemcitabine transport and metabolism proteins predict survival times of patients treated with gemcitabine for pancreatic adenocarcinoma. Gastroenterology, 143, 664-74 e1-6. https://doi.org/10.1053/j.gastro.2012.06.006
  19. Mini E, Nobili S, Caciagli B, et al (2006). Cellular pharmacology of gemcitabine. Ann Oncol, 17, v7-12. https://doi.org/10.1093/annonc/mdj941
  20. Nakagawa N, Murakami Y, Uemura K, et al (2013). Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gemcitabine-based chemotherapy after operative resection. Surgery, 153, 565-75. https://doi.org/10.1016/j.surg.2012.10.010
  21. Nakahira S, Nakamori S, Tsujie M, et al (2007). Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. Int J Cancer, 120, 1355-63. https://doi.org/10.1002/ijc.22390
  22. Neoptolemos JP, Stocken DD, Bassi C, et al (2010). Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA, 304, 1073-81. https://doi.org/10.1001/jama.2010.1275
  23. Oettle H, Post S, Neuhaus P, et al (2007). Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA, 297, 267-77. https://doi.org/10.1001/jama.297.3.267
  24. Ohtaka K, Kohya N, Sato K, et al (2008). Ribonucleotide reductase subunit M1 is a possible chemoresistance marker to gemcitabine in biliary tract carcinoma. Oncol Rep, 20, 279-86.
  25. Peters JL, Sutton AJ, Jones DR, et al (2006). Comparison of two methods to detect publication bias in meta-analysis. JAMA, 295, 676-80. https://doi.org/10.1001/jama.295.6.676
  26. Siegel R, Naishadham D and Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  27. Stang A (2010). Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 25, 603-5. https://doi.org/10.1007/s10654-010-9491-z
  28. Traverso LW (2006). Pancreatic cancer: surgery alone is not sufficient. Surg Endosc, 20, S446-9. https://doi.org/10.1007/s00464-006-0052-1
  29. Ueno H, Kiyosawa K and Kaniwa N (2007). Pharmacogenomics of gemcitabine: can genetic studies lead to tailor-made therapy? Br J Cancer, 97, 145-51. https://doi.org/10.1038/sj.bjc.6603860
  30. Valsecchi ME, Holdbrook T, Leiby BE, et al (2012). Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma? BMC Cancer, 12, 104. https://doi.org/10.1186/1471-2407-12-104
  31. Van Laethem JL, Hammel P, Mornex F, et al (2010). Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/ GERCOR phase II study. J Clin Oncol, 28, 4450-6. https://doi.org/10.1200/JCO.2010.30.3446
  32. Wang Z, Li Y, Kong D, et al (2009). Acquisition of epithelialmesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway. Cancer Res, 69, 2400-7. https://doi.org/10.1158/0008-5472.CAN-08-4312
  33. Wonganan P, Chung WG, Zhu S, et al (2012). Silencing of ribonucleotide reductase subunit M1 potentiates the antitumor activity of gemcitabine in resistant cancer cells. Cancer Biol Ther, 13, 908-14. https://doi.org/10.4161/cbt.20843
  34. Xie H, Jiang W, Jiang J, et al (2013). Predictive and prognostic roles of ribonucleotide reductase M1 in resectable pancreatic adenocarcinoma. Cancer, 119, 173-81. https://doi.org/10.1002/cncr.27715
  35. Ying JE, Zhu LM, Liu BX (2012). Developments in metastatic pancreatic cancer: is gemcitabine still the standard? World J Gastroenterol, 18, 736-45. https://doi.org/10.3748/wjg.v18.i8.736

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