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Correlation between RAS Test Results and Prognosis of Metastatic Colorectal Cancer Patients: a Report from Western Iran

  • Payandeh, Mehrdad (Cancer Research Center, Kermanshah University of Medical Sciences) ;
  • Shazad, Babak (Cancer Research Center, Kermanshah University of Medical Sciences) ;
  • Sadeghi, Masoud (Cancer Research Center, Kermanshah University of Medical Sciences) ;
  • Shahbazi, Maryam (Oncology-Pathobiology Line, Partolab Pathological and Molecular Laboratory)
  • Published : 2016.06.01

Abstract

In the patients with metastatic colorectal cancer (mCRC), RAS testing is the first step to identify those that could benefit from anti-EGFR therapy. This study examined associations between KRAS mutations and clinicopathological and survival data in Iranian patients with mCRC. Between 2008 to2015 in a retrospective study, 83 cases of mCRC were referred to the Clinic of Medical Oncology. The mean follow-up was 45 months that there were 27 deaths. The 3 patients that did not complete follow-up were censored from the study. KRAS and NRAS were analyzed using allele-specific PCR primers and pyrosequencing in exons 2, 3 and 4. Multivariate survival analysis using Cox's regression model was used for affecting of variables on overall survival (OS). The mean age at diagnosis for patients was 57.7 (range, 18 to 80 years) and 61.4% were male. There was no significant different between prognostic factors and KRAS mutation with wild-type. Also, There was no significant different between KRAS mutation and KRAS wild-type for survival, but there was a significant different between KRAS 12 and 13 mutations for survival (HR 0.13, 95% CI 0.03-0.66, P=0.01). In conclusion, the prevalence of KRAS mutations in CRC patients was below 50% but higher than in other studies in Iran. As in many studies, patients with KRAS 12 mutations had better OS thn those with KRAS 13 mutation. In addition to KRAS testing, other biomarkers are needed to determine the best treatment for patients with mCRC.

Keywords

KRAS;NRAS;metastatic colorectal cancer;survival;western Iran

References

  1. Allegra CJ, Rumble RB, Hamilton SR, et al (2016). Extended ras gene mutation testing in metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy: american society of clinical oncology provisional clinical opinion update 2015. J Clin Oncol, 34, 179-85. https://doi.org/10.1200/JCO.2015.63.9674
  2. Al-Kuraya KS (2009). KRAS and TP53 mutations in colorectal carcinoma. Saudi J Gastroenterol, 15, 217-9. https://doi.org/10.4103/1319-3767.56087
  3. Brink M, Weijenberg MP, de Goeij AF, et al (2005). Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study. Int J Cancer, 114, 824-30. https://doi.org/10.1002/ijc.20775
  4. Bokemeyer C, Bondarenko I, Makhson A, et al (2009). Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol, 27, 663-71. https://doi.org/10.1200/JCO.2008.20.8397
  5. Inoue Y, Saigusa S, Iwata T, et al (2012). The prognostic value of KRAS mutations in patients with colorectal cancer. Oncol Rep, 28, 1579-84. https://doi.org/10.3892/or.2012.1974
  6. Lievre A, Bachet J, Le Corre D, et al (2006). KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res, 66, 3992-5. https://doi.org/10.1158/0008-5472.CAN-06-0191
  7. Liu X, Jakubowski M, Hunt JL (2011). KRAS gene mutation in colorectal cancer is correlated with increased proliferation and spontaneous apoptosis. Am J Clin Pathol, 135, 245-52. https://doi.org/10.1309/AJCP7FO2VAXIVSTP
  8. Li Z, Chen Y, Wang D, et al (2012). Detection of KRAS mutations and their associations with clinicopathological features and survival in Chinese colorectal cancer patients. J Int Med Res, 40, 1589-98. https://doi.org/10.1177/147323001204000439
  9. Margonis GA, Kim Y, Spolverato G, et al (2015). Association between specific mutations in KRAS codon 12 and colorectal liver metastasis. JAMA Surg, 150, 722-9. https://doi.org/10.1001/jamasurg.2015.0313
  10. Modest DP, Stintzing S, Laubender RP, et al (2011). Clinical characterization of patients with metastatic colorectal cancer depending on the KRAS status. Anticancer Drugs, 22, 913-8. https://doi.org/10.1097/CAD.0b013e3283493160
  11. Neumann J, Zeindl-Eberhart E, Kirchner T, et al (2009). Frequency and type of KRAS mutations in routine diagnostic analysis of metastatic colorectal cancer. Pathol Res Pract, 205, 858-62. https://doi.org/10.1016/j.prp.2009.07.010
  12. Omidifar N Md, Geramizadeh B Md, Mirzai M Ms (2015). K-ras mutation in colorectal cancer, a report from southern Iran. Iran J Med Sci, 40, 454-60.
  13. Payandeh M, Sadeghi E, Sadeghi M, et al (2015a). Chronic myeloid leukemia in patient with local recurrence colon cancer: a case report. Int J Cancer Research, 11, 197-200. https://doi.org/10.3923/ijcr.2015.197.200
  14. Payandeh M, Sadeghi M, Sadeghi E, et al (2015b). Analysis of KRAS, BRAF and NRAS in Patients with Colorectal Cancer: the First Report of Western Iran. Am J Cancer Prevent, 3, 19-22.
  15. Payandeh M, Sadeghi M, Sadeghi E (2016). The report of KRAS mutation and NRAS wild-type in a patient with thyroid metastasis from colon cancer: a rare case report. Iran J Pathol, 11, 71-5.
  16. Russo A, Rizzo S, Bronte G, et al (2009). The long and winding road to useful predictive factors for anti-EGFR therapy in metastatic colorectal carcinoma: the KRAS/BRAF pathway. Oncol, 77, 57-68. https://doi.org/10.1159/000258497
  17. Roock WD, Vriendt VD, Normanno N, et al (2011). KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer. Lancet Oncol, 12, 594-603. https://doi.org/10.1016/S1470-2045(10)70209-6
  18. Sameer AS, Chowdhri NA, Abdullah S, et al (2009). Mutation pattern of K-ras gene in colorectal cancer patients of Kashmir: a report. Indian J Cancer, 46, 219-25. https://doi.org/10.4103/0019-509X.52956
  19. Shen H, Yuan Y, Hu HG, et al (2011). Clinical significance of K-ras and BRAF mutations in Chinese colorectal cancer patients. World J Gastroenterol, 17, 809-16. https://doi.org/10.3748/wjg.v17.i6.809
  20. Tan C, Du X (2012). KRAS mutation testing in metastatic colorectal cancer. World J Gastroenterol, 18, 5171-80.
  21. Wilson PM, Labonte MJ, Lenz HJ (2010). Molecular markers in the treatment of metastatic colorectal cancer. Cancer J, 16, 262-72. https://doi.org/10.1097/PPO.0b013e3181e07738
  22. Yokota T, Shibata N, Ura T, et al (2010). Cycleave polymerase chain reaction method is practically applicable for V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS)/Vraf murine sarcoma viral oncogene homolog B1 (BRAF) genotyping in colorectal cancer. Transl Res, 156, 98-105. https://doi.org/10.1016/j.trsl.2010.05.007

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