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自噬蛋白LC3B和上皮-间质转化标志物在胃癌中的表达及临床意义

Expression and clinical significance of autophagic protein LC3B and EMT markers in gastric cancer.

作者信息

Wang Juan-Yi, Wu Tao, Ma Wu, Li Shuo, Jing Wen-Jiang, Ma Jun, Chen Dong-Mei, Guo Xiao-Jie, Nan Ke-Jun

机构信息

Department of Oncology, 3201 Affiliated Hospital of Medical College of Xi'an Jiaotong University, Hanzhong, Shaanxi, People's Republic of China.

Department of Gynecologic Cancer, Shaanxi Province Tumor Hospital, Xi'an, Shaanxi, People's Republic of China.

出版信息

Cancer Manag Res. 2018 Jun 11;10:1479-1486. doi: 10.2147/CMAR.S164842. eCollection 2018.

Abstract

BACKGROUND AND AIM

Gastric cancer (GC) is a fatal malignancy with high rate of recurrence and metastasis. Here, we investigated the correlations between the expression of autophagic protein LC3B and 2 epithelial-mesenchymal transition-related proteins (E-cadherin and Vimentin) and the clinicopathological factors and prognosis of patients with GC.

MATERIALS AND METHODS

The expression of LC3B, E-cadherin, and Vimentin in GC samples (110 cases) and paracarcinoma tissues (40 cases) was analyzed using the Oncomine databases and further detected by immunohistochemistry. The correlations among these markers expression and clinicopathological features in GC were analyzed. The patients were followed for survival analysis.

RESULTS

Compared to the nontumor tissues, the expression of LC3B and Vimentin proteins were significantly elevated in GC tissues, but the E-cadherin expression was decreased (all <0.05). Interestingly, LCB expression was positively correlated with Vimentin (=0.320, =0.001) and negatively associated with E-cadherin expression (= -0.484, <0.001) in GC. The expression of these markers was closely related to tumor differentiation, T classification, TNM stage, and lymph node metastasis (all <0.05). Furthermore, survival analyses and screening Kaplan-Meier plotter database revealed that GC patients with high LC3B and Vimentin expression levels had a poorer clinical outcome than those with low expression. Conversely, high E-cadherin expression was linked with favorable overall survival (all <0.05, log-rank test). Multivariate survival analysis demonstrated that LC3B, E-cadherin, and Vimentin expression were independent prognostic factors of GC patients.

CONCLUSION

LC3B, E-cadherin, and Vimentin may play an important role in the tumorigenesis of GC, and these marker expressions may serve as additional prognostic indicators for overall survival of patients. The interactions of autophagy and epithelial-mesenchymal transition in GC merits further investigation.

摘要

背景与目的

胃癌(GC)是一种具有高复发率和转移率的致命恶性肿瘤。在此,我们研究了自噬蛋白LC3B与2种上皮-间质转化相关蛋白(E-钙黏蛋白和波形蛋白)的表达与胃癌患者临床病理因素及预后之间的相关性。

材料与方法

利用Oncomine数据库分析110例胃癌样本和40例癌旁组织中LC3B、E-钙黏蛋白和波形蛋白的表达,并通过免疫组织化学进一步检测。分析这些标志物表达与胃癌临床病理特征之间的相关性。对患者进行生存分析。

结果

与非肿瘤组织相比,胃癌组织中LC3B和波形蛋白的表达显著升高,但E-钙黏蛋白的表达降低(均P<0.05)。有趣的是,在胃癌中LCB表达与波形蛋白呈正相关(r=0.320,P=0.001),与E-钙黏蛋白表达呈负相关(r=-0.484,P<0.001)。这些标志物的表达与肿瘤分化、T分期、TNM分期及淋巴结转移密切相关(均P<0.05)。此外,生存分析和筛选Kaplan-Meier plotter数据库显示,LC3B和波形蛋白表达水平高的胃癌患者临床结局比低表达患者差。相反,E-钙黏蛋白高表达与良好的总生存期相关(均P<0.05,对数秩检验)。多因素生存分析表明,LC3B、E-钙黏蛋白和波形蛋白表达是胃癌患者的独立预后因素。

结论

LC3B、E-钙黏蛋白和波形蛋白可能在胃癌的发生中起重要作用,这些标志物的表达可能作为患者总生存期的额外预后指标。胃癌中自噬与上皮-间质转化的相互作用值得进一步研究。

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