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

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.

The prevalence of KRAS mutation in colorectal cancer patients in Iranian population: A systematic review and meta-analysis study

“…All studies included 1814 CRC patients that mean age of the patients was 57.5 years. In more studies, the prevalence of CRC in males was more than females (Amirifard et al, 2016;Bishehsari et al, 2006;Dolatkhah et al, 2016;Naseri et al, 2016;Omidifar et al, 2015;Payandeh et al, 2016;Roudbari et al, 2016;Shemirani et al, 2011;Tameshkel et al, 2016;Vakil et al, 2016). Number of mutations in codon 12 and 13 and also mutant amino acid in codon 12 has been shown in Table 1 that Gly is normal amino acid in codon 12 and can change to other amino acids.…”

“…All studies are case-control studies published between 2006 and 2016. Six studies were studied from Tehran (Central of Iran) (Bishehsari et al, 2006;Roudbari et al, 2016;Shemirani et al, 2011;Sobhani et al, 2010;Tameshkel et al, 2016;Vakil et al, 2016), one study from Shiraz (Southwest of Iran) (Omidifar et al, 2015), two studies from Kermanshah (Western of Iran) (Amirifard et al, 2016;Payandeh et al, 2016), one study from Tabriz (Northwestern of Iran) (Dolatkhah et al, 2016), and one study from South Khorasan (Eastern of Iran) (Naseri et al, 2016). All studies included 1814 CRC patients that mean age of the patients was 57.5 years.…”

Frequency of NRAS Gene Mutation in Wild Type KRAS and BRAF Colorectal Cancers; a Single Center Study

“…To the best of our knowledge only two published studies have been reported from Iran about the frequency of NRAS in KRAS and BRAF mutation negative CRCs. 17 , 18 In this study, we want to identify NRAS mutations rate and spectrum (at codons 12, 13, and 61) in 52 KRAS and BRAF wild type during 5 years (2011-2015) in the hospitals affiliated to Shiraz University of Medical Sciences as the largest referral center in south of Iran.…”

A novel KRAS gene mutation report in sporadic colorectal cancer, from Northwest of Iran

“…They suggested that these mutation types may confer more aggressive phenotype due to the functional differences associated with different amino acid substitutions, and then resulting protein from these mutation types. Our reported novel KRAS mutation G10V had the same amino acid change, but the prognosis of the patient was not as poor as their report and he had a good response to treatment [6,12]. Further experimental and cohort studies about any association between different KRAS mutation types and biological behaviors are needed to substantiate this theory.…”