Correlation Between The HPSE, VEGF Tissues And Their Prognostic Value Proteins Expression In Gastric Cancer

Background:Carcinoma of stomach is one of the most common cancers and the fourth most frequently diagnosed malignancy worldwide. Gastric cancer is the first leading cause of cancer-related deaths in Japanese males. In the United States, over 21, 260 new cases were diagnosed in 2007, deaths caused by gastric cancer exceeded 11, 210 in the same year. The death rate in China is 25.2 per hundred thousand populations (male: 32.8/100, 000 and female: 17/100, 000) .The incidence amongst Chinese males is 1.9 times higher than females; compared to the Western European countries and the United states, they are about 4.2-7.9 and 3.8-8.0 times higher, respectively. In most of the countries where no effective screening programmes are established to aid the early diagnosis of asymptomatic patients, many are diagnosed with poor prognosis at the late stage of their diseases. Surgical operations, radiotherapy and chemotherapy are not able to significantly increase the survival time and quality of life for end stage gastric cancer patients. Therefore, improvement in early diagnosis, seeking new therapeutic targets and new prognosis indicators is the most promising way forward in gastrointestinal cancer research. Objectives:1 .Determine the tissue expressions of HPSE and VEGF proteins in stomach tissuesamples from 103 gastric adenocarcinoma patients and 20 healthy individuals thenanalyze their correlation with the disease;2.Analyze HPSE and VEGF protein expressions in gastric cancers and theircorrelation with various clinical and pathological parameters;3.Retrospectively analyze HPSE and VEGF protein expressions and their correlationwith the survival time of gastric cancer patients, in order to provide a hypotheticalbase for clinical prognosis;4.Evaluate the feasibility of targeting HPSE and VEGF proteins in gastric cancermolecular therapies, in order to provide a hypothetical base for target therapy forgastric cancers.Methods:1.Data from 103 gastric adenoma patients with full follow-ups were collected. Control data are collected from stomach tissues form 20 healthy individuals.2.Tissue expressions of HPSE and VEGF proteins were determined by Immunohistochemistry method(EliVision^TM two step kit) in 103 gastric adenoma and 20 healthy stomach tissue samples.3.Correlations between the expressions of HPSE and VEGF proteins and various clinical and pathological parameters were analyzed using SPSS13.0 software.Results:1.HPSE and VEGF proteins were detected in 57.3% (59/103) and 46.6% (48/103) amongst the 103 tissue samples of gastric adenoma patients, respectively. Both proteins were undetectable using this method in the 20 healthy control samples (p<0.05) . 2.There is no significant correlation between HPSE, VEGF protein expression and the patients' gender, age, size and site of the tumor and the degree of differentiation(P>0.05) . HPSE and VEGF protein expressions correlate with tumor's infiltration depth, lymph node metastasis, distal metastasis and pathological stages (p<0.05), implying that positive HPSE and VEGF expressions are possible indicators for serosal infiltration, lymph node and distal metastasis.3.The median survival time for patients with HPSE or VEGF protein expression is 11.0 months and 12.0 months respectively. The difference is statistically significant(p<0.05) compared to HPSE or VEGF negative patients whose median survival time is 70.0 months and 70.0 months respectively. Interestingly a COX model analysis has indicated that there is no significant difference between HPSE and/or VEGF expressions and the prognosis of gastric cancer (p>0.05) .4.The expressions of HPSE and VEGF proteins are positively correlated in gastric cancers (r=0.675, p<0.05) .Conclusions:1. The significantly higher expressions of HPSE and VEGF protein in gastric cancer compared to normal stomach tissue imply that HPSE and VEGF proteins are able to serve as two specific molecular markers for gastric cancers.2.HPSE and VEGF expression possibly promotes the infiltration and metastasis involving in the lymph node metastasis of gastric cancers. Expressions of both proteins may be used as molecular markers to predict relapse and metastasis status. 3.Patients with negative HPSE, VEGF protein expressions had a significantly longer median survival time compared to HPSE, VEGF positive patients. This implies that HPSE, VEGF may stimulate the growth of gastric cancer, resulting in the shortening of patient survival time.Therefore HPSE and VEGF can be used as indicators for gastric cancer prognosis.4.Because of the co-inductive nature of HPSE and VEGF proteins in gastric cancers,their co-expression may serve as an indicator for gastric cancer patients.