| Background: In the past ten years,the incidence of esophageal cancer is still high,surgical resection is still the main means for the treatment of esophageal carcinoma.For patients with advanced esophageal cancer,surgical treatment alone can not achieve the biological significance of radical cure,multidisciplinary treatment has become the main treatment for patients with advanced cancer.Neoadjuvant chemotherapy and targeted therapy in recent years as a popular means of treatment,especially in the progression of esophageal carcinoma and its clinical value has been widely recognized,but to evaluate its curative effect and patient group selection is still a lot of controversy.In the development of the second generation sequencing technology,the use of new types of increasingly sophisticated technology,to explore the curative effect of chemotherapy new evaluation markers,noninvasive,accurate and efficient prediction and classification of patients with esophageal cancer,is a hot direction of medicine under the guidance of comprehensive treatment of esophageal cancer,has important clinical significance.At present,study on the application value of free DNA in esophageal cancer is less,have been reported in patients with esophageal cancer can be detected in the peripheral blood of free tumor associated DNA,and plasma cel free DNA detection can be used as a non-invasive evaluation biomarkers for esophageal squamous cell cancer,and cell free DNA(cf DNA)detection of second generation sequencing technology based on the study on evaluating the curative effect of chemotherapy and prognosis of patients with esophageal cancer have been reported.This study examined the content and esophageal cancer related gene cf DNA in the process of chemotherapy patients by monitoring esophageal cancer,the potential of cf DNA as to evaluate the efficacy and prognosis of esophageal cancer patients with chemotherapy diagnosis index.Part Ⅰ The relationship between the cf-DNA concentration in plasma and the clinicopathological character in patients with esophageal squamous cell cancerObjective: To analyze the relationship between the cf DNA concentration in plasma of patients with esophageal squamous cell cancer and clinicopathological characters.Material&Methods: 30 patients with esophageal squamous cell cancer who underwent surgical treatment in the 1st ward area of thoracici surgery department in Zhengzhou University Cancer Hospital were enrolled in this study.All the clinical records were collected and the plasma samples were collected from biological specimen bank.The cf DNA of the plasma samples were measured.The relationship between the clinical and pathological characters and the concentration of plasma cf DNA was analyzed.Results: 30 patients enrolled in present study,and the cf DNA concentration in all the palsma samples was measured successfully using Nanodrop methods of quantitative analysis.The concentration of cf DNA in the plasma of 30 patients is 0.128±0.107ng/ul(0.09-0.51ng/ul).The cf DNA concentration in plasma of the two groups(≥60 years old Groupand and <60 years old Group were 0.188±0.104ng/ul、0.174±0.116ng/ul(p=0.764).The cf DNA concentrations in plama of male and female patient were 0.184±0.1040ng/ul and 0.180±0.115ng/ul(p=0.823).The cf DNA concentrationin in plasma of those patients with or without smoking histry were0.184±0.1040ng/ul and 0.180±0.115ng/ul(p=0.823).The cf DNA concentraton in plasma of those patients with or without drinking histry were 0.184±0.108ng/ul and 0.181±0.109ng/ul(p=0.830).The cf DNA concentration in plasma of those patients with or without malignant tumor family histry were 0.208±0.155ng/ul and 0.176±0.095ng/ul(p=0.097).The cf DNA concentration in plasma of those patients whose nidus lied in the upper/middle/lower 1/3 thoracic esophagus were 0.231±0.045ng/ul,0.161±0.067ng/ul and 0.130±0.018ng/ul(p=0.559).The cf DNA concentration in plasma of those patients with IIa、IIb、IIIa、IIIb disease were 0.184±0.108ng/ul,0.178±0.094ng/ul,0.181±0.109ng/ul and 0.161±0.067ng/ul(p=0.102).The cf DNA concentration in plasma of those patients with well/moderately/poorly differentiated tumor were 0.157±0.078ng/ul,0.185±0.110ng/ul and 0.199±0.131ng/ul(p=0.449).The cf DNA concentration in plasma of those patients with or without lymph nodes mestasis were 0.168±0.063ng/ul and 0.193±0.132ng/ul(p=0.058).All the 30 patients were divided in two groups(Big tumor group and Small tumour group)according to the median of tumor volume,the cf DNA concentration in the two goup were 0.220±0.132ng/ul and 0.145±0.056ng/ul(p=0.006).Acording to result of the correlation analysis,cf DNA level had no significant correlation with TNM stage,but shown positive correlation with tumor volume(r=0.381,P=0.038).Conclusions: The concentration of cf-DNA in plasma of patients with esophageal squamous cell cancer were positively correlated with tumor burden,and there were no significant correlation between the concentration of cf-DNA and TNM stage of tumor,gender,age of patients,location of tumor,stage.Part Ⅱ The selection of adjuvant chemotherapy benefit population using plasma ct-DNA level and gene mutation related tumor in patients with esopheal squamous cell cancerObjective: To screen the gene SNP of chemosensitivity for the patients with esophageal squamous cell cancer,to explore the feasibility of prognose the chemosensitivity using single-nucleotide polymorphisms(SNPs)and cf-DNA.Methods: The data of 14 patients who underwent adjuvant chemotherapy including 7 patients who evaluated as CR/PR and 7 patients who evaluated as PD/SD during the period from March,2016 to May,2016 at the 1st Unit of the Dept.of Thoracic Surgery in Henan Cancer Hospital.The plasma samples of the patients of the 14 patients were obtained from the bank of Biobank of Henan Cancer Hospital and withdraw the cell-free DNA from the plasma samples,the differentia of the gene variation between the chemosensitity Group(CR/PR Group)and control Group(PD/SD Group)was analyzed using Next Generation Sequencing(NGS).Results: The gene variation and variation burden between the chemosensitivity Group(CR/PR Group)and the control Group(PR/SD Group)were significantly different(p=0.0006),the variation burden of the control Group(PD/SD Group)was higher the chemotherapy group(CR/PR Group).Signal path analysis demonstrated that the P53 signal path was the most enriched signal path in the different gene variation between the two group.The variation of copy number and differentia between the two group is significant different.The copy number and variation frequency of the different gene in the patients’ cf DNA who were in the chemosensitivity Group(CR/PR group)were significant higher than that in the control Group.Conclusions:There was significant different between the single nucleotide variation and the aberrance of gene copy number in the patients group with chemotsensitivity(CR/PR Group)and the control group(PD/SD Group).This discovery is helpful to built the model for evaluating the chemosensitivity of the patients who undergo adjuvant chemotherapy.This is significant because it may help doctor to select the benefit population who will undergo the adjuvant cheomotherapy. |
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