The Factors Affecting The Prognosis And Cause Of Death Of The Early Esophageal Squamous Cell Carcinoma And The Relationship Between Variations Of Rs1and The Different Cancer Stages

1Background and purposeEarly stage of the esophageal squamous cell carcinoma (ESCC) has such characteristics for the lesions confined to the mucosa and submucosa without lymph node metastasis (Tis～T1N0M0). And it has a good effect after the operation with more than90%of the5year survival rate. It is an effective way to improve the survival rate and reasonable treatment for the early detection of esophageal cancer (EC). However, the rate of early diagnosis of EC is still not high (10%), and the accumulation of early EC cases is very difficult. And it is hard to representativeness for the most of the existing literatures, which only contain dozens of cases. Now it is badly needed to the large sample for the statistical analysis of the clinical and pathological features of early EC and the relationship of the prognosis. It is good for increasing the understanding of early EC for improving clinical diagnosis and more reasonable treatment, and providing a strong theoretical support and basis. This research is supported by the Henan Province Key Laboratory for esophageal cancer of the largest esophageal cancer cases database in the world, finishing in340thousands cases of esophageal carcinoma, finding2387cases of the patients with early ESCC with clear clinical and pathological features. By the statistics of ESCC and prognostic factors, especially the analysis of death cause of death, it is benefitial to understand the impact of the prognostic factors of the disease, providing some basis and theoretical support to enhance the reasonable treatment of early ESCC. In addition, the research group finds that it is closely related to prognosis of the RS1polymorphism with high risk of ESCC by genome-wide association analysis (GWAS). This study is devoted to find the relationship between clinical features of the ESCC and RSI in3074cases, and the relationship between the site and the different pathological stages, so as to providing a new molecular marker for the early diagnosis of esophageal cancer.2Materials and Methods2.1Subjects2.1.1The factors affecting the prognosis and cause of death of the early esophageal squamous cell carcinoma2387cases were diagnosed as early stage of the ESCC with radical resection in1975to2012, which came from Henan Province esophageal biological samples database.1325male patients (mean58.84±8.04years),1062females (mean59.33±7.90years), male:female=1.3:1, and the median age is59years old.2.1.2The relationship between variations of rsl and the different cancer stages3074cases were used for GWAS technology, which is famous for finding important gene polymorphisms, to identify the real genetic loci significantly associated with prognosis.1863male patients (mean60.51±9.04years),1211females (mean61.35±9.16years old male), Male:female=1.5:1. And the median age is60years,1year younger than the women’s. 2.2Households survey, Verification hospital data and Follow-upThrough household survey or phone follow-up to record the patient’s basic and survival information, and in accordance the information of the patients with treatment of hospital to review, supplement of the treatment modalities and the pathological diagnosis. Follow-up time was from the date of surgery to Feb18,2014.2.3Diagnostic criteria of early ESCCIt can be seen as superficial mucosal lesions by endoscopy, such as erosion, plaque and mucosal rough, no late metastasis phenomenon; biopsy and postoperative pathology reports for ESCC, infiltration of carcinoma in situ, mucosa, mucosa or submucosa, without lymph node and distant metastasis. It is the0phase and I phase (phase0:Tis NO MO, phase Ⅰ:T1NO MO).2.4Collecting blood samples, DNA extraction and Taqman genotypingIn the case of informed consent of patients, each patient acquisited5ml EDTA anticoagulant peripheral venous bloods. The Qiagen Flexi Gene DNA extraction kit to extract blood cell genomic DNA. Application of Taqman (?) genotyping analysis technique.2.5Statistical analysisThe data was analyzed by SPSS19.0. The chi-square test was applied to analyze the count data; Kaplan-Meier method and Log-rank test for the differences between the different survival groups; Influencing factors using Cox proportional hazards regression model to analyze the prognosis of patients with ESCC. a=0.05was considered as the test standard.3Results 3.1SurvivalThe survival rate of patients with early ESCC after1year,2year,3year,4year,5years,10years,20year was:93%,88%,85%,82%,78%,65%,53%. The average survival time was5.70±4.26years. And the median survival was4.86years.3.2The relationship between clinicopathologic features and prognosisSingle factor analysis showed, family history, pathological staging, infiltration degree, degree of differentiation, gross type, tumor length, tumor location, high and low incidence area, degree, age of onset had significant relationship with the prognosis of esophageal carcinoma which meant statistical significance (P<0.05). The removed lymph node number had no significant relationship with the prognosis of esophageal carcinoma which showed no statistical significance (P>0.05). And the extent of tumor invasion, gross type, tumor length, age of onset were the biggest factors affecting on the prognosis (P<0.05). Younger patients compared to older ones were the better prognosis factor for survival(HR=0.237,95%CI:0.15-0.38); The smaller tumor length compared to the larger was the better prognosis factor (HR=0.649,95%CI:0.49-0.86); The plaque type was the better prognosis factor(HR=0.599,95%CI:0.48-0.74). Infiltration of mucosa layer compared to the submucosa was the better prognosis factor(HR=0.529,95%CI:0.42-0.67).3.3Analysis the cause of deathIn the526dead patients, the tumor cause contains418cases (79.47%), and108cases was non tumor cause of death (20.53%). The tumor causes for the cancer cells metastasis, included lung, liver, bone metastasis, and tumor recurrence. Non cancer death cause includes anastomotic fistula, pulmonary infection, cardiovascular and cerebrovascular diseases. Through the analysis of patients with various clinical and pathological factors, the older patient has a higher proportion of non-neoplastic causes of death (χ2=18.881, P=2.89E-04); and the proportion of the non tumor causes death for workers and cadres more than farmers (χ2=4.697, P=0.03); Within3years of the dead patients, non tumor death caused ones had the higher proportion of the shorter survival time (χ2=36.408, P^6.07E-06). With the prognosis of early EC, in this study,60patients had been died in1year. In the60patients, tumor and non cancer causes of death were42and18cases. It was significant difference to the svival time between the cancer and non cancer death cause. By early ESCC HE slices of123cases during2006-2008, it was found that the existence of small vascular tumor thrombus in HP sections of3dead cases in the yao cun esophageal cancer hospital. It suggested the possibility of the early hematogenous metastasis, which might be one of the reasons for its poor survival.3.4The relationship between AAAAA gene RS1polymorphism and ESCC in different clinical phenotypesHardy-Weinberg balance test showed that the genotypes of the RS1locus in genetic equilibrium distribution in this population (χ2=1.142, P=0.28). The distribution of RS1genotype and gender, age, family history, the degree of differentiation, T stage, N stage, tumor length, gross type of early and late in the gross type was not significant (P>0.05). TNM classified as early stage, the same correlation significantly, there was statistically significant (χ2=9.703, P=0.046).But in the three different genotype group, it is no statistical significance between the early, middle and late stages (P>0.05).4Conclusion4.1The extent of tumor invasion, gross type, tumor length, age of onset is important factor affecting the prognosis of early ESCC patients with postoperative. The shallower for the degree of infiltration, gross type of protuberant, the smaller of the tumor length, the younger onset of early ESCC cases may have better postoperative prognosis.4.2The reason of death in a short time after operation for early ESCC, on one hand, it can be attributed to non cancer factors, such as medical accident, operation complications. On the other hand, it is caused by tumor distant metastase and recurrence. In addition, merely operation is not enough for some early ESCC patients for short time death. Timely chemotherapy may be needed for those patients.4.3rsl has not a significance relationship with the prognosis and the different clinical stages. So it is needed to explore more sensitive indexs for judgement on the clinical stages and prognosis.