Detection Of KRAS Mutation And Advanced Colorectal Cancer Targeting Prognosis Assessment

Colorectal cancer is the third in the worldwide incidence of cancer, thesecond in the mortality rate, about yield1.2million new patients a year. InChina, the colorectal cancer has become the third in tumor diseases of the causeof death. The direction of development of the treatment of colorectal cancer inactive and comprehensive treatment of surgery, surgery resection of the primarytumor, relieve obstructive symptoms caused by the tumor. Chemotherapy aftersurgery in recent years, combined with immunotherapy, traditional Chinesemedicine, gene therapy, especially targeted therapy for more and more clinical.The incidence of colorectal cancer is a multi-stage, multi-step involved in thecomplex process of the formation of a variety of oncogenes and tumorsuppressor gene activation or deactivation. Chemotherapy will improve survivalof advanced colorectal cancer, but some patients will be the emergence ofresistance, not more than six months once the resistance reported survival ofadvanced colorectal cancer. Therefore colorectal cancer gene mutationsdetection, expect to find for colorectal cancer targeted therapy will greatlyimprove the prognosis of advanced colorectal cancer, reduce the incidence ofresistant to adverse events, and new program individualized treatment forcolorectal cancer. The proto-oncogene KRAS important molecules in the EGFRdownstream signaling pathway, the KRAS gene mutations in the2exonunrestricted proliferation of tumor cells can be induced to get rid of the normal EGFR signaling pathway. KRAS gene mutations will affect the effect of EGFRinhibitors. NCCN will recommend cetuximab combined with chemotherapy asfirst-line treatment of advanced colorectal cancer patients with wild-type KRASgene bevacizumab combined with chemotherapy is recommended as first-linetreatment of advanced colorectal cancer (KRAS mutations). KRAS genemutation detection and cetuximab and bevacizumab in patients with advancedcolorectal cancer, the safety and efficacy of most of the data sources formforeign reports, the KRAS gene mutation of Chinese human colorectal featuresand application cetuximab single little of anti bevacizumab reported data.Objective:KRAS genetic testing of patients with colorectal cancer to identify thecharacteristics of Chinese human colorectal KRAS gene mutations, the KRASgene mutation and the clinicopathological factors between the relationshipbetween different KRAS gene mutation subtypes and prognosis. Retrospectiveobservational analysis of cetuximab combined with chemotherapy, bevacizumabin combination with chemotherapy, targeted therapy of the safety and efficacy inpatients with advanced colorectal cancer. Provide a theoretical basis for targetedtherapy of colorectal cancer.Method:Part I:78patients with colorectal cancer paraffin specimen selected by HEstaining cancer tissue paraffin blocks, followed by the application of PCR-SSCPin78cases of colorectal cancer were12,13codon on the2exon of KRAS genemutation detection. Between the analysis of the KRAS gene mutations and theclinicopathological factors. Patients were followed up, follow-up data line survival analysis to analyze the relationship between the subtypes and theprognosis of the the KRAS gene mutant and wild type prognostic differences,different mutations. Part II: Retrospective analysis cetuximab combined withchemotherapy and bevacizumab combined with chemotherapy in the treatmentof patients with advanced colorectal cancer. Explore the efficacy and safety offirst-line treatment of non-first-line-line treatment.Results:Part I:78patients with colorectal cancer, KRAS gene mutations in a totalof26cases, the mutation rate of33.3%(26/78). KRAS gene mutations aresingle base point mutations, not detected in two or more nucleotide mutations orother forms of mutations. The GA mutation frequency of the highest of20cases(20/26,76.9%); followed by GT mutations in five cases (5/26,19.2%); GCmutation in only1patient (1/26,3.9%). KRAS gene on the12th codonmutations in19cases(73.1%,19/26), a total of three different mutations way:GGT-GAT mutations in13cases (13/26,50%), glycine Gly replaced by asparticacid Asp; GGT-GTT mutation of the five cases (5/26,19.2%), glycine Glyreplaced with valine Val; GGT-GCT mutation (1/26,13.9%), Glycine Glyreplaced with alanine Ala. The13th codon mutations in7cases (26.9%,7/26),are GGC-GAC mutation (7/26,26.9%), glycine Gly replace the aspartic acidAsp. Amino acid substitutions, Gly substitute the Asp highest frequency,accounting for76.9%(20/26); followed by Gly replaced by Val accounted for19.2%(5/26); Gly with Ala the lowest frequency of only3.8%(1/26).Relationship between KRAS gene mutation and the clinicopathological factors:the degree of differentiation of the KRAS gene mutations and colorectal cancer (differentiation in poorly differentiated52.6%vs27.1%, P <0.05), livermetastases (liver metastases46.7%vs no liver Transfer to25%, P <0.05) related.78patients followed up: the KRAS gene wild type patients the average survivaltime of35.05months, the KRAS gene mutations in patients with type averagesurvival time is25.72months, there is a statistically significant (P <0.05).KRAS gene codon mutation in the12th with an average survival time was25.69months, the13th codon mutations in patients with an average survival time is20.67months, no statistically significant. Univariate analysis showed that thethe KRAS gene mutations in colorectal cancer patients with poor prognosis areclosely related (P <0.05), multivariate analysis showed that liver metastasesKRAS gene mutations, tumor poorly differentiated independent prognosticfactors (P <0.05, P <0.05, P <0.05).Part II: A retrospective analysis of72patients admitted to our hospital withadvanced colorectal cancer. Receiving cetuximab combined with chemotherapyin the treatment of38cases, the overall efficiency of34.2%, and the diseasecontrol rate was63.2%. First-line treatment efficiency of50%. The diseasecontrol rate was87.5%. Non-first-line response rate was22.7%, the diseasecontrol rate was45.5%. First-line treatment of the disease control rate was thesecond-line treatment, there is a statistically significant (P <0.05). The first-linetreatment efficiency was higher than the second-line treatment, no statisticallysignificant. Receive bevacizumab combined with chemotherapy in the treatmentof34cases, the overall efficiency of29.4%,64.7%of the overall disease controlrate. The first-line treatment efficiency of42.9%. The disease control rate was92.8%. The effective rate of20%non-first-line therapy, disease control rate of 45%. The first-line treatment of the disease control rate was higher than thesecond-line treatment, a significant (P<0.05). The first-line treatment of thedisease control rate was higher than the second-line treatment, but no significant(P>0.05). The cetuximab group bevacizumab group point of view no significantdifference between the frequency of occurrence of adverse reactions in thegastrointestinal tract and bone marrow suppression. Cetuximab combined withchemotherapy in first-line treatment group the median survival time was16months, non-first-line treatment, the median survival time was12months, astatistically significant (P<0.05). Bevacizumab combined with chemotherapy infirst-line treatment group, the median survival time is24months, and thefirst-line treatment median survival of17.5months, a significant (P<0.05).Cetuximab combined with chemotherapy group, the median survival time was14months, bevacizumab in combination with the chemotherapy group’s mediansurvival of18.5months (P>0.05). No statistically significant. Univariateanalysis showed: the site of advanced colorectal cancer with a poor prognosisare closely related (P<0.05). Multivariate analysis revealed that tumor site inpatients with advanced colorectal cancer, and accept in newly diagnosed whenfirst-line targeted therapy is an independent prognostic risk factors (P <0.05, P<0.05).Conclusion:KRAS gene mutations in patients with colorectal cancer commonlyoccurring mutation frequency in line with the current international reports,higher mutation frequency of33.3%. KRAS gene mutation in poorlydifferentiated colorectal liver metastasis. Multivariate analysis revealed that liver metastases, the KRAS gene mutations, tumor poorly differentiated independentprognostic factors. KRAS gene mutation that prompts a poor prognosis inpatients with colorectal cancer.Whether to accept patients with advanced colorectal cancer with cetuximabor bevacizumab treatment, select the first-line treatment of the disease controlrate and survival period were better than the non-first-line treatment. The site ofadvanced colorectal cancer with a poor prognosis. Multivariate analysis revealedthat tumor location and whether to accept the targeted therapy in newlydiagnosed, when first-line prognosis independent risk factor. Cetuximab andbevacizumab application of advanced colorectal cancer is safe and effective.