K-ras Gene In Codon12,13of Exon2Mutation Status Is Associated With Clinical And Pathological Characteristics, Chemotherapy Effect And The Outcome Of Colorectal Cancer

Objective: The prevalence of colorectal cancer has rised in recent years. Since theprecocious symptoms of colorectal cancer is not prominent. Resulted in the majority ofpatients already belongs in advanced transmutative colorectal cancer diagnosed. Some ofthese patients had lose the best time of surgery. Part of patients with colorectal cancer may beless than8months of survival time. Colorectal maintain a high relapse rate. Nearly half of thecombined presence of liver metastases of colorectal cancer recurrence. Long-term treatmentof clinical medical staff looking forward to the prospect of colorectal cancer. In recent years,for the treatment of colorectal cancer and related technical approach has been significantprogress. But chemotherapy is still an important means of treatment of advanced colorectalcancer. Traditional chemotherapy Such as leucovorin, fluorouracil, irinotecan, can improvethe quality of life of patients and increases the survival of patients. However, its therapeuticeffect is still unsatisfactory, and adverse reactions heavier conventional chemotherapy, andrelatively poor patient tolerance.Bevacizumab is a recombinant humanized anti-vascular endothelial growth factor(VEGF) monoclonal antibody, it can specifically block the vascular endothelial growth factor(VEGF) binding with VEGFR, inhibition of vascular endothelial cell growth and proliferationof new blood vessels. Thereby inhibiting tumor growth and progress.This test is designed to compare gene KRAS codon12and13mutations distribution.Relationship simultaneous contrast KRAS gene mutations in codon12,13andclinicopathological features of colorectal cancer patients, bevacizumab treatment and survivaltime. To provide better solutions and individualized targeted therapy to determine theprognosis of patients with colorectal cancer KRAS gene mutations in codons12and13. Methods:The topic of the patients admitted to our hospital were68cases of colorectal cancer fromMarch2011to September2012, which has passed into the group of patients diagnosed withcolorectal cancer pathology. Cases of clinical and pathological data extracted on demand,which including patient age, sex, clinical stage, taking their efficacy, Clinical treatmentoptions, etc. Application of polymerase chain reaction amplification and sequencing to detectKRAS gene mutation status of codons12,13, And compare the KRAS gene mutations incodons12,13and clinicopathological characteristics of patients with colorectal cancer,bevacizumab treatment and survival time relationship. The resulting test data input SPSS19.0statistical analysis software for various rates χ2test. Using the Kaplan-Meier method to assesssurvival rates among the groups with survival function curve drawing application. CompareKRAS codon12and13mutations in gene relationships with non-small cell lung cancer casessurvival time of patients. All statistical results of P<0.05was said that the difference wasstatistically significant.Results:1. Into the group of patients,40cases of male patients,28cases of female patients.Median age55. Less than55years old in37cases, over55years old in31cases. TNM stageⅡb of28patients, Ⅲ+Ⅳof40patients. source of specimens: primary foci specimens was30.88%(21/68); metastatic lymph nodes biopsy specimens was20.59%(14/68),both primaryfoci specimens and metastatic lymph nodes biopsy specimens was48.53%(33/68).2. Our study had completed68cases of patients with colorectal cancer K-ras gene incodon12,13of exon2mutation detection, of which,56cases located at the codon12of exon2,12cases located at the codon13of exon2.3. The K-ras gene in codon12,13of exon2muatation rate was significantly higher inmale (58.82%) than in female (41.18%). The mutation rate was significantly lower in TNMstage Ⅱb (41.18%) than in stage Ⅲ+Ⅳ (58.82%). The mutation rate was significantly higherin underwent surgery patients (64.71%) than without operation patients（35.29%）. Themutation rate was significantly higher in primary foci and metastatic lymph nodes (48.53%)than primary foci nodes（30.88%）or metastatic lymph nodes（20.59%）. However, patients’ age (54.41%vs45.59%), diameter(48.53%vs51.47%), eminence type and ulcerative type(44.12%vs55.88%), poorly differentiated and highly differentiated (42.65%vs57.35%),rightcolon, transverse colon, left colon, rectum, two and above (8.82%vs5.88%vs44.12%vs36.76%vs4.41%), ECOG score (45.59%vs54.41%), mutation rate difference between thegroups was not statistically significant.4.68cases of patients were enrolled after at least four cycles of therapy, ORR and DCRtest group patients were52.94%and85.29%. ORR and DCR control patients were29.41%and61.76%. Objective between the test group and the control group was (P=0.049) anddisease control rate (P=0.028) were significantly.5. The progression-free survival in patients with the experimental group was significantlyhigher in K-ras gene mutations than in control group.6. In68cases with colorectal cancer that had accurate survival data,34cases with theexperimental group and34cases with control group. The median survival time in two groupswere72weeks (95%CI,67.5-76.5weeks) and50weeks (95%CI,43.6-56.4weeks)respectively, There are significant differences in survival between the two groups.Conclusions:1. In this study, completed a total of68cases of K-ras gene codon12and13mutationsalleles detected in patients with colorectal cancer, of which the codon12of exon2mutationrate is82.35%, among which GGT mutated GAT is the most common type, the codon13ofexon2mutation rate is17.65%, among which GGC mutated GAC is the most common type.2. Colorectal cancer K-ras gene mutation at codon12and13with gender, TNM stage,whether surgical treatment was statistically significant. Colorectal cancer patient’s age, tumorsize, tumor gross morphology, degree of differentiation, ECOG score, tumor location, andwhether the merger lymph node metastasis, distant metastasis mutations and K-ras genecodon12and13, among the group, the difference was not statistically significant.3. K-ras gene in codon12,13of exon2mutation is a predictor of Bevacizumab efficacy.4. K-ras gene in codon12,13of exon2mutation is an independent predictor of survival of colorectal cancer.