| 1 Background and objectiveChinese esophageal cancer has the typical characteristics of geographical distribution,which results in the distinct high-and low-risk incidence areas,and the morbidity and mortality of high-risk areas can be as much as 500 times than lowrisk areas[1].While the high-risk incidence areas mainly located in mountainous and rural areas,the urban areas are relatively rare.More than 97% of the histological types of Chinese esophageal cancer is esophageal squamous cell carcinoma(ESCC),which is significantly different from that in western countries that esophageal adenocarcinoma is the most common type.The occurrence and development of esophageal cancer is a multi-stage pathological process which involves in many factors and many genes.Nutritional deficiency,especially vitamins and trace elements,is one of the major risk factors for esophageal cancer in China [2].Therefore,esophageal cancer in our country is known as a "poor disease".Exposure to nitrosamines,mycotoxinscontaminated and human papillomavirus(HPV)infection are also considered as important risk factors for esophageal cancer in the high-risk incidence areas for esophageal cancer in China [3].Therefore,patients with ESCC in high-risk incidence areas for esophageal cancer,especially in rural regions,may be more likely to be exposed to environmental risk factors.In contrast,patients with esophageal cancer in urban regions may be likely to have a lower risk of exposure to nitrosamines and biological risk factors.Furthermore,the urban patients have a better condition than rural patients in the diet,nutritional status,economic level and medical resources.This may be one of the reasons why ESCC is rare in urban regions,and thus may have a certain impact on the prognosis.However,there are very few reports on survival analysis of patients with ESCC in rural and urban areas.The analysis of P53 gene mutation spectrum showes that aflatoxin B can cause the third base change which is localed in codon 249,so as to form the special mutation of p53 gene;nitrosamines in the environment can also cause P53 mutation [4-5].Wang et al [6] reported that the alteration in the signal transduction pathways of P53-Rb is one of the important molecular mechanisms in the process of esophageal cancer.There is a significant difference in the degree of exposure to risk factors in patients with ESCC from rural and urban areas.However,the difference in the expression of P53 in the ESCC tissue of rural and urban patients has not been well studied,and the study of the relationship between expression of P53 and clinicpathogic characteristics in the two groups is still rare.Therefore,this study through the comparative analysis of 41,520 cases with ESCC from rural and urban regions to discuss survival difference and its influencing factors between rural and urban patients,and to study the expression of P53 in the two groups and its’ significance,thus providing feasible bases for prevention and control,early warning for high-risk groups and related molecular detection of ESCC.2 Materials and methods 2.1 Object of studyIn this study,the general information,pathology details,clinical information and follow-up results of the 41,520 cases were all from the clinical databases of 500,000 esophageal and gastric cardia carcinomas(1973-2015)of the Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital,Zhengzhou University.In the total of 41520 cases,37,968 cases were rural patients(91.4%)and 3,552 cases were urban patients(8.6%).The rural patients include 23,685 male patients with an average age of 58.98±8.64 and 14,283 female patients with an average age of 59.51±8.49.The urban patients include 2,400 male patients with an average age of 60.65±9.10 and 1,152 female patients with an average age of 62.31±9.13.In this study,all the patients received radical resection of esophageal cancer.2.2 Clinical information collection and follow upClinical information of all the patients were from the medical records in the hospitals where patients were treated,including general information,detailed address and contact information,and so on.All the patients have detailed postoperative pathologic diagnosis.And the clinical and pathologic information has been checked and supplemented from the related hospitals.Patients were followed up by telephone,household surveys,asking village doctors and other methods.The last follow-up time was April 2016 and the success rate was 92%.2.3 Methods1)The clinical date of 37,968 rural patients and 3,552 urban patients with ESCC were analyzed retrospectively,including the patients’ gender,age,gross type,differentiated degree,lymph node metastasis,stump cancer,TNM stage,high-and low-risk incidence areas.2)56 cases of rural patients and 29 cases of urban patients were selected randomly.The expression of P53 protein in the ESCC tissue and corresponding normal esophageal tissue which is 5cm above from the tumor mass was deteceted respectively by immunohistochemistry.The relation between the expression of P53 and the clinical features of patients with ESCC from rural and urban regions was analysed respectively.Then further analysis was made relating to the expression of P53 in the ESCC tissue and the effect on prognosis for the two groups.3)The data was analyzed by SPSS 21 software analysis system.Patients’ gender,age,and the clinicopathologic characteristics were analyzed by Chi-square test;Survival time was calculated by year.Life-table method was used to evaluate the 1 year,3 year and 5 year survival rates of patients;Kaplan-Meier and Log-rank methods were used in the analysis of survival differences;and Cox proportional hazards regression model was used to analyze the main influencing factors for survival.3 Results 3.1 The distribution of clinical characteristics of the patients from rural and urban regionsIn the total of 41,520 ESCC petients,37,968 cases were rural patients(91.4%),which were far higher than that of urban patients(3,552 cases,8.6%).The proportion of male and female patients with ESCC from rural and urban regions was 1.7:1 and 2.1:1 respectively,which has a significant difference(P<0.05).The mean age at time of diagnosis of rural male(58.89±8.64)and female patients(59.51±8.49)were smaller than that of urban male(60.65±9.10)and female patients(62.31±9.13)(P<0.05).The proportion of the rural patients from the high-risk incidence areas(65%)for esophageal cancer was much higher than that of urban patients(46.7%)(P=0.000).11.8% of the rural patients were diagnosed as the early cancer(0+Ⅰstage),which was much lower than that of the urban patients;but the proportion of the advanced cancer(Ⅱ+Ⅲ+Ⅳstage)was obviously higher than the urban patients’(χ2=25.787,P=0.000).3.2 Comparative analysis of survival and its influencing factors in patients with esophageal squamous cell carcinoma in rural and urban areasLife-table analysis showed that the 1 year,3 year and 5 year survival rates of the patients from the rural and urban regions were 90%,69%,55% and 87%,64%,52%,respectively.Kaplan-Meier and log-rank analysis showed that the rural patients had a better overall survival than that of the urban patients(χ2=15.503,P=0.000).Further analysis revealed that the male and female of the rural patients with ≥50 years old in middle stage(Ⅱa、Ⅱb stage)had a better survival than that of the urban patients(male: χ2=14.868,P=0.000;female: χ2=8.025,P=0.005),but the there was no survival difference between the rural patients and urban patients in the early and terminal stage(Ⅲ、Ⅳstage)of the cancer(P>0.05).3.3 The analysis of the multivariate Cox proportional hazards regression modelCox regression model analysis incicated that the independent risk factors for the survival of the rural patients with ESCC were gender,age,high-and low-risk incidences areas,TNM staging,differentiated degree and tumor sites;but the independent risk factors for urban patients’ survival were gender,age,high-and lowrisk incidence areas and TNM staging.The overall Cox regression model analysis for both rural and urban patients ESCC revealed that the male,age with ≥50 years old,urban regions,low-risk incidence areas,TNM staging,poor differentiated degree,upper tumor,positive stump cancer were independent risk factors for the survival with ESCC.And the female,rural regions,high-risk incidence areas,well differentiated degree,negative stump cancer were the protective factors for prognosis of ESCC.3.4 Expression and prognostic analysis of P53 in patients with esophageal squamous cell carcinoma in rural and urban areasThe expression of P53 protein in the normal esophageal tissue and the orresponding ESCC tissue of the 56 rural patients were 7.1%(4/56)and 64.3%(36/56)respectively,there was a significant difference of them(P<0.05).Like the rural patients,the expression of P53 protein in the normal esophageal tissue and the orresponding ESCC tissue of the 29 urban patients were 6.9%(2/29)and 61.1%(18/29)respectively,and the difference between them was significant(P<0.05).However,the expression of P53 protein in the ESCC tissue between rural and urban patients was similar(rural: 64.3%;urban: 62.1%)(P>0.05).The expression of P53 protein in the ESCC tissue has no relation with gender,age,differentiated degree and lymph node metastasis in both rural and urban patients.The survival for both rural and urban ESCC patients with positive and negative expression of P53 protein in the esophageal caner was similar(rural: P=0.686;urban: P=0.605).The positive expression of P53 protein in the caner tissue was not an independent risk factor for the survival of rural patients,urban patients and overall patients.4 Conclusions1)The rural patients had a better overall survival than that of the urban patients;2)The male,age with ≥50 years old,urban regions,low-risk incidence areas,TNM staging,poor differentiated degree,upper tumor,positive stump cancer were independent risk factors for the survival with ESCC.3)The positive expression of P53 in esophageal carcinoma was much higher than that of normal esophageal tissue,so the expression of P53 can be used as a molecular marker of esophageal cancer detection;but the expression of P53 protein in the ESCC tissue between rural and urban patients was similar.The positive expression of P53 protein in the caner tissue was not an independent risk factor for the survival of ESCC,and the traditional pathological information was still the vital reference for the survival of ESCC. |
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