Analysis Of The K-ras Gene Mutation Relations To Its Clinicopathology Factors And Systematic Review In Ctal Cancer

Part 1 Systematic review of K-ras gene mutation relation with its clinicopathology significance in colorectal cancerObjective:To investigate the K-ras gene mutation relations with its clinicopathology fatcrs in colorectal cancer with a systematic review.Methods: Published studies were collected in Cochrane Library,Pubmed,Embase,American Society of Clinical Oncology(ASCO),CNKI,Wang fang databases,VIP,CBM and quality of the included original studies were assessed.Meta-analysis of enrolled studies were performed by Renvman 5.3 software.Results: Totally 29 research were collected for this systematic review,included 5210 colorectal cancers and 2459 K-ras gene mutation.Results of Meta analysis showed that the K-ras gene mutation associated with preperative {OR=1.78,95%CI(1.27--2.49),P=0.0008},lymph node metastassis {OR=1.61,95%CI(1.27-2.05),P<0.0001)},TNM stages {OR=0.71,95%CI(0.56--0.88),P=0.002},but not asscociated with tumor location {OR=0.94,95%CI(0.72-1.24),P=0.68)},distant organ metastasis {OR=1.39,95%CI(1-1.91),P=0.05},carcinoma differentiation{OR=0.94,95%CI(0.72-1.24),P=0.68} and tumor size{OR=0.88,95%CI(0.63-1.22),P=0.44}.Conclusions: ⑴The K-ras gene mutation rate was higher in patients with colorectal cancer who had positive CEA level than that regular CEA level in preoperative.The mutation of K-ras gene was correlated with preoperative CEA level.⑵III+IV patients had higher K-ras gene mutation rate compared with I+II patients by TNM stages with colorectal cancer.Mutation of K-ras gene may increase the risk of invasion,lymph node metastasis playing a promoting role with colorectal cancer.⑶K-ras gene mutation may be uncorrelated to tumor location,distant organ metastasis,carcinoma differentiation and tumor size。Part 2 Analysis of detection the K-ras gene mutation relation to its clinicopathology factors in colorectal cancerObjective : To investigate the incidence of K-ras gene mutation in colorectal cancer and explore its correlation with clinicopathological factors in colorectal cancer.Methods: 120 cases of fresh colorectal cancer primary tumor specimens which were treated by open or laparoscopic surgery in the First Affiliated Hospital of Guang Xi hospital Medical University were collected to detect the K-ras gene mutation by using x-TAG liquid chip technology.Analysis of K-ras gene mutation associated with gender,family history,age,nation,blood type,course of disease,hypohemia,serum albumin,Hbs Ag,CEA,FOB,tumor location,distant organ metastasis,tumor size,histopathological type,gross type,carcinoma differentiation,infiltration depth,lymph node metastassis,vascular and lymphatic invasion,perineural invasion,TNM stages were performed by SPSS15.0 software.Results: In 120 cases,the K-ras gene mutation rate was 35%(42/120),in which male was accounted for 54.17%(65/120)and female in 55 cases was accounted for 45.83%(55/120).Inside,the rate codon 12 and codon 13 was respectively 30 cases and 9cases,accounting for 74.3% and 24.3% in all 42 mutation cases.And 3 cases appeared codon 13 and codon 13 mutation at the same time,accounted for 7.14%(3/42).Results of SPSS15.0 analysis showed that ⑴ the K-ras gene mutation did not associated with gender,family history,age,nation,blood type,course of disease,hypohemia,serum albumin,FOB,tumor size,histopathological type,gross type,carcinoma differentiation, infiltrationdepth,perineural invasion(p>0.05).⑵The rate of K-rasmutation was 48.8%(20/41)in positive Hbs Ag,which was higher than that of negative(22/79),and the difference was statistically significant(χ2=5.199,P=0.023).The incidence of K-ras mutation in CEA was 42%(34/81)higher than that of CEA negative group 20.5%(8/39),and the difference was statistically significant(χ2=5.330,P=0.021).In the primary site of the tumor,the incidence of K-ras gene mutation in the right side colon was 46.9%(23/49)higher than that of left side colon(19/71)of 26.8%,and the difference was statistically significant(χ2=5.189,P=0.023).Furthermore,K-ras gene mutation with distant organ metastasis patients incidence rate was 60%(27/45)significantly higher that 20% without distant organ metastasis(15/75),and the difference was statistically significant(χ2=19.780,P=0.000).K-ras gene mutation with vascular and lymphatic invasion incidence rate was 71.4%(25/35)significantly higher that 20% without distant metastasis(17/85),and the difference was statistically significant(χ2=28.832,P=0.000).Finally,in the TNM stage,K-ras gene mutation in I+II patients with colorectal cancer incidence rate was 18.5%(5/27)compared with 39.8% incidence of stage III+IV(37/93)was significantly lower,the difference was statistically significant(χ2=4.160,P=0.041),also too the lymph node metastassis.Conclusions: ⑴In this study,the mutation rate of K-ras gene in colorectal cancer patients was consistent with that of most of the country,which indicated that K-ras gene mutation is a common event in the process of colorectal cancer.⑵ the K-ras gene mutation did not associated with gender,family history,age,nation,blood type,course of disease,hypohemia,serum albumin,FOB,tumor size,histopathological type,gross type,carcinoma diffe-rentiation,infiltration depth,perineural invasion.⑶The K-ras gene mutation in colorectal cancer was correlated with Hbs Ag,preoperative CEA level,primary tumor site,distant organ metastasis,lymph node metastassis,vascular invasion and TNM stage(P < 0.05).It is suggeste that the positive rate of K-ras gene mutation may be higher in these patients.Part 3 Analysis of detection the PI3 KCA gene mutation relation to its clinicopathology factors and K-ras in colorectal cancerObjective:To investigate the incidence of PI3 KCA gene mutation in colorectal cancer and explore its correlation with clinicopathological factors in colorectal cancer and its pathway.Methods: 120 cases of fresh colorectal cancer primary tumor specimens which were treated by open or laparoscopic surgery in hospital were collected to detect the PI3 KCA gene mutation by using x-TAG liquid chip technology.Analysis of PI3 KCA gene mutation associated with gender,age,nation,,CEA,tumor location,tumor size,histopathologicaltype,gross type,carcinoma differentiation,infiltration depth,lymph node metastassis,vascular and lymphatic invasion,TNM stages,K-ras were performed by SPSS15.0 software.Results: ⑴In 120 cases,the PI3 KCA gene mutation rate was 24.2%(29/120).Inside,the rate 9 exon and 20 exon was respectively 16 cases and 13 cases,accounting for 55.2% and 44.8% in all 29 mutation cases.And 6 cases of these patients showed simultaneous mutations in codon 12 or 13 of the k-ras gene,accounted for 20.7%(6/29).Results of SPSS analysis showed that the PI3 KCA gene mutation associated with CEA significantnegative correlation(r=-0.298,P=0.034).⑵The rate of PI3 KCA mutation associated with TNM stage significantnegative correlation(r=-0.310,P=0.029).Furthermore,PI3 KCA mutation associated K-ras gene mutation significant positive correlation(r=0.337,P=0.016).Conclusions: ⑴In this study,the mutation rate of PI3 KCA gene in this location colorectal cancer case group was 24.2%,which was consistent with most regional reports.It was indicated that the PI3 KCA gene mutation was not an accidental event in the occurrence of colorectal cancer.⑵The PI3 KCA gene mutation in colorectal cancer was correlated with,preoperative CEA level and TNM stage(P < 0.05)in this region.It is suggeste that patients with regular PI3 KCA gene were more likely to have normal CEA levels,and the earlier stage of diagnosis was confirmed.⑶ There may be signaling pathways between K-ras and PI3KCAPTEN-AKT pathways,which need to be further confirmed.