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CagA、c-Met、PI3K和Beclin-1在胃癌中的表达及其与预后的关系和临床价值。

Clinical value of CagA, c-Met, PI3K and Beclin-1 expressed in gastric cancer and their association with prognosis.

作者信息

Huang Xiaojun, Wang Chaoqun, Sun Jinmin, Luo Jun, You Jiangzhou, Liao Linchuan, Li Mingyuan

机构信息

Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Department of Pathogenic Biology and Immunology, School of Medicine, Hubei University for Nationalities, Enshi, Hubei 445000, P.R. China.

出版信息

Oncol Lett. 2018 Jan;15(1):947-955. doi: 10.3892/ol.2017.7394. Epub 2017 Nov 13.

Abstract

Gastric cancer (GC) is the fourth most common type of malignant tumor worldwide, and causes the second highest number of cancer-associated mortalities in 2012. Gastric tumorigenesis is a multistep and multifactorial process. In the present study, tissue microarray and immunohistochemistry analysis were used to detect cytotoxin-associated gene A (CagA), c-Met, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and Beclin-1 expression in 121 GC tumors and 120 normal gastric tissues. The clinical relevance and prognostic implications of CagA, c-Met, PI3K and Beclin-1 expression in GC patients were analyzed. Furthermore, the Cox proportional hazards model was performed to indicate the independent prognostic factors for GC patients, including various clinicopathological parameters and CagA, c-Met, PI3K and Beclin-1 expression. The results indicated that CagA-positive H. pylori infection, c-Met, PI3K and Beclin-1 may have major roles in the oncogenesis, invasion and lymph node metastasis of GC. The disease-free survival rate was negatively associated with the expression of c-Met and CagA in tissues, and was positively associated with Beclin-1 expression. Overall survival was also negatively associated with the expression of c-Met and PI3K, and was positively associated with Beclin-1 expression. This indicated that c-Met and Beclin-1 may be independent and efficient biomarkers for predicting the DFS of patients with GC. Furthermore, in CagA-positive H. pylori infection-associated GC, c-Met expression was significantly upregulated and Beclin-1 expression was significantly downregulated. CagA-positive H. pylori infection therefore associated with the c-Met signaling pathway and the suppression of autophagy in the neoplasia, invasion and metastasis of GC.

摘要

胃癌(GC)是全球第四大常见恶性肿瘤类型,在2012年导致的癌症相关死亡人数位居第二。胃癌的发生是一个多步骤、多因素的过程。在本研究中,采用组织芯片和免疫组化分析检测了121例胃癌肿瘤组织和120例正常胃组织中细胞毒素相关基因A(CagA)、c-Met、磷脂酰肌醇-4,5-二磷酸3-激酶(PI3K)和Beclin-1的表达情况。分析了CagA、c-Met、PI3K和Beclin-1在GC患者中的临床相关性及预后意义。此外,采用Cox比例风险模型来确定GC患者的独立预后因素,包括各种临床病理参数以及CagA、c-Met、PI3K和Beclin-1的表达情况。结果表明,CagA阳性幽门螺杆菌感染、c-Met、PI3K和Beclin-1可能在GC的肿瘤发生、侵袭和淋巴结转移中起主要作用。无病生存率与组织中c-Met和CagA的表达呈负相关,与Beclin-1的表达呈正相关。总生存率也与c-Met和PI3K的表达呈负相关,与Beclin-1的表达呈正相关。这表明c-Met和Beclin-1可能是预测GC患者无病生存期的独立且有效的生物标志物。此外,在CagA阳性幽门螺杆菌感染相关的GC中,c-Met表达显著上调,Beclin-1表达显著下调。因此,CagA阳性幽门螺杆菌感染与GC的肿瘤形成、侵袭和转移中的c-Met信号通路及自噬抑制有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0337/5772925/acc29e619f2e/ol-15-01-0947-g00.jpg

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