Clinical Epidemiology And Serum Proteomics Studies In Patients With Gastric Cardia Adenocarcinoma In High Incident Area In Henan Province

Background and objectiveGastric cardia adenocarcinoma (GCA) is one of the most common malignant diseases in Northern China, expecially in Linzhou city and its surround area. The incidence rate of tumors of GCA still keeps in high level. There are multiple phases and factors which participate the development of GCA. ANCHORCHIP technique, MALDI-TOF-MS, and ClinProTools is a new technology of proteomics to detect the spectrum of serum protein expression. In this research, we retrospectively studied gastric cardia adenocarcinoma patients, including clinicopathologic features and the hereditary susceptibility. We used the ClinProt system to detect the spectrum of serum protein in gastric cardia adenocarcinoma patients. We screened related proteins related with live time of gastric cardia adenocarcinoma.Materials and methodsPatients (n=447) enrolled in this study came from high incident area of GCA in Linzhou city and its surround area. Health control group was made up of gastroscopy normal people in the same period. All patients did not have any chemotherapy and radiotherapy. Research objects included age,sex, area, testing time, main complain,、 clinical feature、duration of symptoms、diagnosis method and diagnosis time、 personal history、family history、location of tumor、 pathological types、histological types and the degree of differentiation and TNM. ClinProt system composed of function magnetic bead、ANCHORCHIP technique、MALDI-TOF-MS and ClinProTools bioinformatics method.Empty stomach venous blood were collected from 18 GCC patients and 20 normal people, purified by function magnetic bead. We used MALDI-TOF-MS to screen the expect protein peaks that have related to the onset of gastric cardia adenocarcinoma through analyzing difference protein peaks that had different M/Z in the data base. The permissive error range of molecular weight is< 0.5%.Empty stomach venous blood were collected from 38 GCC patients, purified by function magnetic bead. We used MALDI-TOF-MS to screen the expect protein peaks that have related to the life span of 38 patients with gastric cardia adenocarcinoma.According to the M/Z of different protein peaks, we retrieved the proteins that match with it as the expect proteins of esophageal cancer in SWISS-PROT protein data base by http://us.expasy.org/tools/tagident.html. The permissive error range of molecular weight is<0.5%.Results1.The epidemiology and genetic susceptibility of patients with cardia cancer in high incidence area for gastric cardia adenocarcinomaIn 447 patients with gastric cardia adenocarcinoma,the mean diagnosed age was 58.60±8.80 years,the mean diagnosed age of male patients was 57.47±9.04 years,the mean diagnosed age of female patients was 61.97±8.05 years.Age at diagnosis of gastric cardia adenocarcinoma male patients were earlier than female patients (t=-0.52, P=0.05).In the 447 patients with cardiac cancer,first symptoms of progressive dysphagia 228 cases.If the patient has two or more first degree relatives and/or second degree relatives (including the patient) who suffered from gastric cardia adenocarcinoma, we can define it gastric cardia adenocarcinoma hereditary susceptibility;if the patient has two or more first degree relatives and/or second degree relatives (including the patient) suffered malignant tumor (including esophageal carcinoma), we can define it malignant tumor hereditary susceptibility. Cardiac cancer patients with cardiac cancer TNM staging among all age groups constitute TNM3 period the proportion of the largest (265/447).In the 447 patients with cardiac cancer,325 patients had been found lymph node metastases when they went to see a doctor (including imaging and confirmed after the operation),122 patients didn’t find lymph node metastases. The pathological histological type of cardiac cancer can be divided into squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, undifferentiated carcinoma and other types.Pathological histological type of cardiac cancer had nothing clear correlation with esophageal cancer and cardiac cancer(p>0.05).The carcinoma’s differentiation degree of patients with cardiac cancer can be divided into well-differentiated, moderately differentiated, poorly differentiated, undifferentiation.Differentiation degree had nothing clear correlation with whether the patient had a family history of malignant cancer、 esophageal cancer and cardiac cancer.2. The analysis aboat serum protein expression spectrum of the gastric cardiac cancer patients in the high esophageal cancer incident area in ChinaIn the gastric cardiac cancer group had 13 protein peaks (M/Z:M2369.93Da、 M2066.42Da、M4980.31Da、M2128.37Da、M4964.22Da M4645.87Da、M2394.7Da、 M4112.16Da、M8605.08Da、M4591.45Da、M4299.37Da M2444.97Da M2899.63Da)regulate; but 7 kinds protein peaks(M/Z:M1865.35Da、M1778.51Da、 M1691.73Da、M1881.32Da、M5337.59Da、M5352.67Da、M1450.46Da) down-regulate.The protein peaks (M1865.35Da、M1778.51Da) were screened as category variable to establish category predictive model and to get serum protein mean spectrogram mean value standard deviation and difference. Serum protein sample profile demonstrated that the two protein peaks in gastric cardiac cancer group mean peak obviously just to minor normal control. Two group blood serum samples distributed in two ranges that had significance difference.3. Life span related protein expression spectrum in cardiac cancer patientsThe serum of patients with cardiac cancer who had prolonged survival had significantly higher tendency of 22 kinds of proteins:1866.57Da、3159.66Da、 3957.84 Da、3972.95Da、4112.16Da、4420.42Da、4436.54Da、4574.71Da、 4591.45Da、5905.94Da、 1450.46Da、1778.51Da、2022.6Da、2234.6Da、3883.64Da、 4132.1Da、5670.17Da、5685.49Da、5924.9Da、6934.93Da、7838.62Da、8572.13Da. Prolonged survival related with significantly increased expression of the 2 proteins in cardiac cancer patients:4112.16Da、4591.45 Da; The serum of patients with cardiac cancer who had prolonged survival had significantly lower tendency of 22 kinds of proteins:6649.86Da、8131.92Da、8288.51Da、3380.05Da、3472.8Da、3491Da、 3505.84Da 3772.08Da、5448.65Da、5988.04Da、2070.24Da、3446.47Da、3565.12Da、 4067.61Da、4398.36Da、4744.17Da、6450.97Da、6609.99Da、6811.24Da、8937.92Da.The protein 4067.61Da increased in cardiac cancer patients and decreased significantly with prolonged survival;The protein 5448.65Da downregulated in cardiac cancer patients and also decreased with prolonged survival significantly.That the molecular weight of 4067.61 Da and 5448.65Da protein expressed in cardiac patients is not conducive to the survival of protein.The proteins matched with them were retrieved in SWISS-PROT protein data base to find out the expected proteins related to prognosis.Conclusions1. In the patients with cardiac cancer,the mean diagnosed age was 58.60±8.80 years,the mean diagnosed age of male patients was 57.47±9.04 years,the mean diagnosed age of female patients was 61.97±8.05 yearsAge at diagnosis of cardiac cancer male patients were earlier than female patients (t=-0.52, P=0.05).Most of the first symptom in cardiaccancer showed progressive dyspiaha(228 cases.). Cardiac cancer patients with cardiac cancer TNM staging among all age groups constitute TNM3 period the proportion of the largest (265/447).In the 447 patients with cardiac cancer,325 patients had been found lymph node metastases when they went to see a doctor. Differentiation degree had nothing clear correlation with whether the patient had a family history of malignant cancer、esophageal cancer and cardiac cancer.2. Magnetic bead based sample fractionation and MALDI-TOFMS as a tool to research protein expression map has repeatability and precision.3.13 serum protein are up-regulated, while 7 serum protein are down-regulated in cardiac cancer, these proteins maybe potential tumor markers of cardiac cancer.In the serum of patients with cardiac cancer who had prolonged survival were significantly higher tendency with 22 kinds of proteins trends, in the serum of patients with cardiac cancer who had prolonged survival were significantly lower tendency with 20 kinds of proteins trends, the molecular weight of 4067.61 Da and 5448.65Da protein is expressed in cardiac patients is not conducive to the survival of protein.