| Purpose: As the fifth worldwide malignancy, gastric cancer is the third leading cause of cancer mortality in both sexes. Approximately, one million new cases are diagnosed with gastric carcinoma per year since 2012, causing more than 700,000 deaths annually.Although the mechanism of gastric carcinogenesis is still unclear right now, there are some potential risk factors which might lead to gastric cancer. Reviewing the articles on risk factors will help us to prevent stomach tumor better in the future.The overexpressed in lung cancer 1 (OLC1) was originally identified by Yuan et al in human squamous cell lung tumors. Based on previous discoveries, elevated expression of OLC1 protein promoted oncogenesis and predicted a poor prognosis in many human cancers. We wondered if OLC1 could be a potential marker for gastric cancer,particularly for gastric adenocarcinoma. We have performed this retrospective study and been intended to reveal the correlation between OLC1 and clinicopathologic parameters and prognosis in patients with gastric tumors. Additionally, considering only total protein expression was well studied in human cancers, effects of different subcellular OLC1 expression were ignored in the past. Thus, it was another focus of our study to elucidate the influences of different subcellular expression of OLC1 on gastric cancer, especially on gastric adenocarcinoma.Experimental Method: Both overall and subcellular expression of OLC1 was evaluated by immunohistochemistry(IHC) via tissue microarrays from total 393 samples. The samples included samples from gastric cancer (N=383), from gastric atypical hyperplasia (N=4) and from benign gastric disease (N=6). The Kaplan-Meier method and Cox’s proportional hazard model were exerted to further explore the correlation between OLC1 and prognosis.Results: Total overexpression of OLC1 was significantly associated with stage (P =0.004) and differentiation (P = 0.009), and only the strong total expression could predict a poor prognosis (HR = 1.31, P = 0.04). There were significant associations found between nuclear overexpression and tumor invasion depth (P = 0.002), lymph node (P< 0.001), stage (P = 0.004). differentiation (P < 0.001) and smoking history (P = 0.045).Furthermore,over-expressed nuclear OLC1 protein could be an independent risk factor for gastric adenocarcinoma (univariate: HR = 1.43, P = 0.003; multivariate: HR=1.39,P = 0.011).Conclusion : Rather than the total expression, nuclear overexpression of OLC1 was correlated with most clinicopathological parameters and could predict a poor overall survival as an independent factor for prognosis,which made it a more effective and sensitive biomarker for gastric adenocarcinoma.Significance: This is the first time to investigate the correlation between OLC1 and clinicopathologic parameters, as well as prognosis in patients with gastric adenocarcinoma. Additionally, it is the first time to reveal the different influences of various subcellular localizations of OLC1 on human cancers. OLC1, especially that localized in the nucleus,has a great chance to be a novel treatment target for gastric adenocarcinoma and even to help prevent gastric adenocarcinoma. |
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