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The Different Expression Of Ki-67、Nm23 And Multidrug Resistance Proteins Between Left And Right Colon Cancer And Its Clinical Significance

Posted on:2018-11-02Degree:MasterType:Thesis
Country:ChinaCandidate:J TangFull Text:PDF
GTID:2334330515489910Subject:Surgery
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Background and objective :Colon cancer has become one of most common therioma of digestive system.According to the GLOBOCAN2012 statistics released by WHO [1],one million 360 thousand new cases of colorectal cancer were estimated in the world in2012,and the number of cases was third in all malignant tumors.The number of death cases were 694 thousand,ranking the leading cause of death due to cancer in the top fifth.The number of colorectal cancer incidence and mortality accounted for first of the total in China.For the treatments of colorectal cancer is still limited,mainly by surgery,supplemented by chemotherapy,radiotherapy and targeted therapy,but the overall effect of treatment is poor,so looking for individual differences in colorectal cancer and seek accurate treatment is particularly important.In 1990,Bufill[2] divided the colon into the proximal colon and the distal colon at the point at 2/3 of proximal colon transversum,on the basis of the differences between embryonic origin,anatomical(such as arterial supply,venous reflux)and molecular characterization,and therectum belongs to the distal colon.A large number of studies have used this classification method[6-7].Another method of dividing line is splenic flexure of colon.As well as the classification of CALGB80405 [11] was not included the colon transversum.At present,it has been proved that there are many differences in the left and right colorectal cancer,which are mainly manifested in some clinical behavioral characteristics,gene types,survival time and the response to tumor drugs.For example,the existing research [8-9] shows that the microsatellite instability(MSI)are significantly different between left and right colon cancer.The right usually has high-microsatellite instability(MSI-H),but left colon cancer seems to be more microsatellite stability(MSS).Furthermore,MSI-H was found to be associated with a higher degree of malignancy compare to MSI-L(low-microsatellite instability)or MSS,which may have an impact on the sensitivity of anticancer drugs [10].The results of the CALGB80405 study [11] confirmed that metastatic left colon cancer had longer survival compared to right colon cancer,and there was a significant difference in sensitivity of targeted drugs between left and right colon cancer.It can be seen that there are many reports on the differences between left and right colon cancer,but there is still a lack of unified conclusions.In recent years,some studies have shown that the poor prognosis of right colon cancer is also related to the inflammatory response,metastasis potential and itssensitivity to chemotherapy drugs,but there are few studies in this area.Our study will use the method of retrospective study and classification of Bufill,dividing colon into right colon(cecum,ascending colon,hepatic flexure of colon and 2/3 of proximal colon transversum,)and left colon(1/3 of distal colon transversum,splenic flexure of colon,descending colon,sigmoid colon and rectum),making the primary site of different colorectal cancer patients as the research object.The clinical data of the patients were collected and the survival data were collected.The expression of multidrug resistance,proliferation and inhibit metastasis related proteins in colorectal cancer were detected by immunohistochemistry.The study aims to further observe the clinical biological differences between left and right colon cancer,and observe the multidrug resistance protein,inhibit proliferation and metastasis related protein expression,NLR and PLR,as well as their relationship with prognosis of left and right colon cancer.In terms of clinical and molecular biology to further understand the difference between left and right colon cancer,,and to provide the reasonable choice of the treatments to colorectal cancer with different primary sites.Methods: 108 colon cancer patients in the gastrointestinal surgery department in the First affiliated Hospital of Southwestern Medical University during July 1,2013-2016 were included in our retrospective study.All patients were operated in our hospital and postoperativepathological biopsy confirmed as colon cancer,at the same time we got rid of the patients who received preoperative chemotherapy,radiotherapy,biological treatment or other auxiliary treatment.Clinical data of patients including complete blood cell analysis,biochemical test,gastrointestinal tumor markers detection results were collected,according to the clinical data,the patients were divided into right colorectal cancer group and left colon cancer group.Pgp,GST-π,TopoII,TS were selected as index of multiple antibiotic resistance and Ki-67,Nm23 as index of the degree of proliferation and inhibit metastasis respectively.Immunohistochemical method was taken to test its level of expression in colon cancer tissues of the specimens of paraffin from those patients.The overall survival rate(OS)of the patients was chosen for prognosis.Patients were followed up from rehabilitation until October 1,2016,the end of the study or dead.The follow-up period was 1-38 months,with a median follow-up time of 18 months.Result: 1.There are no significant differences in surgery and postoperative chemotherapy between right and left colon cancer,comparable.Univariate analysis showed that gender,preoperative symptoms,preoperative albumin,preoperative PLR,preoperative metastasis,tumor diameter,differentiation and TNM stage were significantly different(P<0.05).Oppositely,there were no significant differences in the age of onset,preoperative NLR,preoperative CEA,serosal involvement,vascular invasion,nerve invasion,postoperative complications,general tumor type and lymph node metastasis.Multivariate analysis showed that were was significant difference in PLR between left and right colon cancer(p=0.04).2.The positive expression rates of Ki-67 in left and right colon cancer were 84.48% and 88%,no significant differences between the two groups(p=0.304).And the positive expression rates of Nm23 in carcinoma of the left colon and right colon were 72.41% and 84%(p=0.32).3.The resistance rates of right colon cancer patients with GST – π,Pgp,TS,TopoⅡ were 48%,63%,32%,46% respectively,left were 26.60%,48.30%,6.90%,31% respectively,And GST-π(p=0.028)and TS(p=0.001)had significant differences in the expression.4.The one、two、three year survival rate of the 108 patients was89.5%,78.8%,and 65.2% respectively.Log-rank test showed that the primary tumor site,TNM stage,distant metastasis,differentiation,vascular invasion,nerve invasion and preoperative NLR were risk factors for the prognosis of colon cancer(P < 0.05).The preoperative NLR was an independent risk factor for the prognosis of colon cancer(HR=4.528,95%CI:0.099-0.909,P=0.033).5.There was no significant difference in overall survival betweenright and left colon cancer patients with stage I-II(p=0.674),But in the stage III-IV(p=0.042).Conclusion:1.There is a significant difference in clinical pathology and prognosis between right colon cancer and left colorectal cancer,especially in patients with stage III-IV tumors,Similar to reported in the literature.2.The level of PLR in the right colon cancer was significantly higher than that of left colorectal cancer,which may be associated with the occurrence of malnutrition,failure and anemia in right colon cancer.3.Right colon cancer drug resistance gene GST-π and TS expression level was significantly higher than that of left colon cancer,suggesting that the increased resistance to chemotherapy.Chemotherapy drug sensitivity test should be put into effect before using Cisplatin and 5-fu.
Keywords/Search Tags:Left colorectal cancer, right colon cancer, multidrug resistance, primary tumor site, prognosis, individualized treatment
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