| 1 Background and objectiveGastric Cardia Adenocarcinoma(GCA)is a common malignant tumor of the upper digestive tract,which is often referred to as "sister cancer" because of its similar regional prevalence and clinical symptoms with esophageal squamous cell carcinoma(ESCC)in northern China.In recent decades,the global incidence of cardia adenocarcinoma has continued to rise,and Chinese and Western scholars have begun to pay more attention to the study of this disease.With the deepening of the research on tumor diseases,researchers and clinicians have realized that different subtypes of the same tumor have different treatment methods and different prognosis effects,which reminds us that we should pay more attention to the understanding of different subtypes of tumors.Therefore,a complete histological classification is of great significance to the deeper understanding of tumor diseases and the realization of personalized prevention and precision treatment in the next step.The occurrence of malignant tumor is a long,complex and changeable process.In the process of canceration in normal tissues,changes in genes and proteins may be the earliest and most critical factors.Cadherins(Cadherins)are a superfamily of proteins that mediate cell-to-cell adhesion in a calcium-dependent manner and play an important role in many organ morphogenesis.PCDH9(Pro-cadherin 9)belongs to the cadherin superfamily.It is a tumor suppressor gene that has been proved in gastric cancer and liver cancer.It can regulate the differentiation and invasion ability of tumors,and its deletion and decreased expression are closely related to the prognosis of patients.In this study,the GCA was divided into five histological types,namely tubular adenocarcinoma,poorly differentiated adenocarcinoma,mucinous adenocarcinoma,papillary adenocarcinoma and signet ring cell carcinoma,according to the different histological morphologies presented by GCA and combined with the diagnosis by clinical pathologists.The clinical characteristics of different histological types of GCA and associated factors with their prognosis were analyzed,and the expression profiles in different histological types and the effects on survival of different histological types were further analyzed in combination with PCDH9 protein.It is expected to provide a theoretical basis for early screening and personalized prevention of GCA.2 Materials and methods2.1 Object of studyAll the research subjects were derived from the clinical information database of 500,000 cases of esophageal cancer(EC)and GCA established by the State Key Laboratory of Esophageal Cancer Prevention&Treatment of the First Affiliated Hospital of Zhengzhou University in 1973.The surgical patients who were pathologically diagnosed as GCA were selected,and the histological classification was clear,and the clinical diagnosis and treatment information of the patients was clear and complete,without the occurrence of other malignant tumors.2.2 Methods1)The clinicopathological characteristics of 4895 patients with different histological types of GCA were retrospectively analyzed,including name,gender,age at diagnosis,home address,smoking history,drinking history,family history,tumor length,degree of tumor differentiation,depth of tumor invasion,lymph node metastasis,and distant organ metastasis,etc.The relationship between each histological type and clinical features was analyzed to explore the prognostic factors of different histological types.2)The pathological tissue sections of 4895 patients with GCA included in the analysis were stained by immunohistochemistry to analyze the expression of PCDH9 protein in different types,and to explore the association between PCDH9 protein expression and the clinical characteristics and prognosis of GCA with different histological types.2.3 Statistical analysisStatistical analysis was performed using SPSS 23.0.The description of the basic clinical characteristics of patients was divided into frequency and percentage.The comparison of classification data was performed by the chi-square test.Univariate survival analysis was based on the Kaplan-Meier method and Log-rank test to analyze the survival rate between groups.A Multivariate Cox proportional risk regression model was used to analyze the independent factors affecting the prognosis of patients with GCA.Test level:a=0.05.3 Results3.1 Clinicopathological features and survival analysis of different histological typesA total of 4895 patients with cardiac adenocarcinoma were included in this study,including 3847 males(78.6%),with an average age of 61.92±8.593 years old at diagnosis.There were 1048 females(21.4%)with an average age of 61.67±8.541 years.The most common histological types were tubular adenocarcinoma in 2440 cases(49.8%),followed by poorly differentiated adenocarcinoma in 1732 cases(35.4%),signet ring cell carcinoma in 291 cases(6.0%),papillary adenocarcinoma in 221 cases(4.5%)and 210 cases(4.3%)of mucinous adenocarcinoma.Through analysis,it was found that gender,age at diagnosis,smoking history,drinking history,tumor family history,and M staging were not significantly different in the distribution of different histological types(p>0.05).There were significant differences in the high and low incidence area,tumor length,tumor differentiation degree,depth of invasion(T stage),lymph node metastasis(N stage),and TNM stage between different histological types(P<0.05).Among patients with tubular adenocarcinoma,the age of diagnosis increases,the patient comes from a high-risk area,the degree of tumor differentiation is reduced,and the positive lymph node metastasis was an independent risk factor for the prognosis of the patient.In patients with poorly differentiated adenocarcinoma,patients came from a high-risk area,and the low degree of tumor differentiation was an independent risk factor for the prognosis of patients,while drinking were an independent protective factor for the prognosis of patients with poorly differentiated adenocarcinoma.Age at diagnosis was an independent prognostic factor in patients with mucinous adenocarcinoma,and the older the patient was at diagnosis,the worse the prognosis.In patients with papillary adenocarcinoma,gender was a factor affecting the prognosis,and the prognosis of women was better than that of men.Among patients with signet ring cell carcinoma,patients come from a high-risk area,and smoking was an independent risk factor for their prognosis.3.2 Expression of PCDH9 protein in different histological types and its relationship with survivalAmong 4895 patients included in the analysis,the overall positive expression rate of PCDH9 protein was 96.1%.Among them,the positive expression rates were 97.6%in tubular adenocarcinoma,95.2%in poorly differentiated adenocarcinoma,92.4%in mucinous adenocarcinoma,98.6%in papillary adenocarcinoma,and 89.4%in signet ring cell carcinoma.The expression of PCDH9 protein was significantly different among different histological types(P=0.000).The survival of patients with positive expression of PCDH9 protein in the five types of GCA tissues was better than those with negative expression.Also,the expression of PCDH9 protein is an independent prognostic factor in patients with tubular adenocarcinoma,poorly differentiated adenocarcinoma,and signet ring cell carcinoma.The prognosis of positive protein expression was better than that of negative protein expression.4 Conclusions4.1 The most common histological type of GCA was tubular adenocarcinoma,and papillary adenocarcinoma and mucinous adenocarcinoma are less common.Papillary adenocarcinoma has the best prognosis among the five histological types,and signet ring cell carcinoma has the worst prognosis.4.2 The independent prognostic factors were different with different histological types of GCA.4.3 The survival of patients with positive PCDH9 protein expression was better than that of those with negative expression,and PCDH9 protein expression was an independent influencing factor for good prognosis in patients with tubular adenocarcinoma,poorly differentiated adenocarcinoma and signet ring cell carcinoma.It can be used as a molecular index to determine the prognosis of patients with GCA. |
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