Abstract

Loss of Heterozygosity (LOH) is commonly considered to be one of a reason when some genes lose their function. Numbers of tumor suppressor genes are existing on the LOH lesion and chromosome 16q24 had been reported as a LOH region in gastric cancer. Little is known about what kind of tumor suppressor genes locates around the position. F-box protein, (FBXO31) is a candidate tumor suppressor gene encoded in chromosome 16q24.3 and LOH of the gene was reported in breast cancer, hepatocellular carcinoma and ovarian cancer but the status of FBXO31 was not analyzed in gastric cancer so far. One hundred twenty-seven pairs of tumor and corresponding normal tissue specimens collected from gastric cancer patients who underwent gastrectomy. Total RNAs were extracted from those samples and the expression of FBXO31 was investigated using real time quantitative RT-PCR analysis. Patients were classified into FBXO31 high expression group and low expression group. Clinicopahological factors were compared between the two groups and importance of FBXO31 was investigated. The standardized expression of FBXO31 was not significantly different between tumor (0.43 ± 0.46) and the corresponding 0.49 ± 0.55 in normal tissue (p = 0.39). Two years survival rate was 77% in FBXO31 high expression group and 54% in low expression group however the chance of survival rate of high expression group was dropped in 5 years (Wilcoxon p = 0.01). Clinicopathological factors were compared between the two groups and peritoneal dissemination was observed significantly higher in FBXO31 low expression group than did in high expression group (p = 0.0398). In order to predict existence of peritoneal dissemination of gastric cancer before surgery, FBXO31 may become a favorite marker for the low risk of peritoneal dissemination.

Highlights

  • Gastric cancer is the second leading cause of cancer death in world wide and the ratio was high in eastern Asia [1]

  • F-box protein, (FBXO31) is a candidate tumor suppressor gene encoded in chromosome 16q24.3 and Loss of Heterozygosity (LOH) of the gene was reported in breast cancer, hepatocellular carcinoma and ovarian cancer but the status of FBXO31 was not analyzed in gastric cancer so far

  • Purpose of this study is to examine the expression status of cyclin D1 and FBXO31 and investigate significance the expression of FBXO31 in gastric cancer

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Summary

Introduction

Gastric cancer is the second leading cause of cancer death in world wide and the ratio was high in eastern Asia [1]. In Japan, modification of diagnostic procedure and upgrading of therapeutic techniques made it possible to remarkably improve the prognosis of the disease and the recent overall five years survival and recurrence free survival rate were accounted for 70% and 63% respectively. Gastric cancer could not be completely cured yet and thousands of newly diagnosed patients lose their lives due to the disease. It will be up to the development of non-surgical treatment if there is a further room for the more modification of gastric cancer therapy. S-1 based chemotherapy was demonstrated to be efficient as an adjuvant chemotherapy for stage II or III gastric cancer patients [3] the effect was not sufficient against far advanced gastric cancer thereby novel therapeutic arms such as molecular targeting drugs should be developed

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