作者：李引，林青雨，钱辰，周侦，翟二涛

单位：中山大学附属第一医院胃肠外科中心，广东 广州 510080

Authors: Li Yin, Lin Qingyu, Qian Chen, Zhou Zhen, Zhai Ertao

Unit：Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China

摘要：

目的 探讨富含亮氨酸重复序列/Ⅲ型纤维连接蛋白4（leucine-rich repeat and fibronectin type Ⅲ domain-containing protein 4，LRFN4）在胃癌组织中的表达情况，并分析LRFN4 表达水平与胃癌患者临床病理参数和预后的关系。方法  收集2017年1月至12月于中山大学附属第一医院胃肠外科中心确诊并行手术治疗的胃癌患者组织标本8组（包含胃癌组织和癌旁正常组织），并选取2004年1月至2005年12月在同一中心行手术治疗的117例胃癌患者术后组织标本制成胃癌组织芯片。分析LRFN4在癌症基因组图谱(the cancer genome atlas, TCGA)数据库胃癌数据集中的表达情况，应用蛋白质印迹法及实时荧光定量聚合酶链反应检测LRFN4 在8组新鲜胃癌组织及癌旁正常组织中的表达，应用免疫组织化学检测LRFN4在胃癌组织芯片中的表达。分析不同LRFN4表达水平的胃癌患者其临床病理参数的差异。应用Kaplan-Meier法分析不同LRFN4表达水平的胃癌患者的预后情况。应用单因素和多因素Cox回归分析法分析胃癌患者预后的影响因素。结果  LRFN4在TCGA数据库胃癌数据集的胃癌组织以及新鲜胃癌组织中呈高表达状态。LRFN4高表达的患者，表现出更大的肿瘤大小以及更为进展的T分期、N分期、M分期和TNM分期（均P＜0.05），其预后也较差（P＜0.001）。单因素和多因素Cox回归分析提示LRFN4在胃癌组织中的高表达是影响胃癌患者预后的独立危险因素(HR=3.898，95%CI 2.273~6.686，P＜0.001)。结论  胃癌组织中LRFN4 高表达与患者较差的预后相关，可能成为预测胃癌患者预后的生物标志物之一。

关键词：胃癌；富含亮氨酸重复序列/Ⅲ型纤维连接蛋白4；癌症基因组图谱数据库；生物标志物；胃癌预后 

Abstract：

Objective To investigate the expression of leucine-rich repeat and fibronectin type Ⅲdomain-containing protein 4 (LRFN4) in gastric cancer tissues and analyze the relationship between LRFN4 expression levels and the clinicopathological parameters as well as the prognosis of gastric cancer patients. Method  8 groups of samples of gastric cancer patients were collected, including gastric cancer and adjacent normal tissue. These patients were diagnosed and underwent surgical treatment at the Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University from January to December 2017. Postoperative tissue samples of 117 gastric cancer patients were collected between January 2004 and December 2005 from the same center to create a gastric cancer tissue microarray. The expression of LRFN4 in the gastric cancer dataset from the cancer genome atlas (TCGA) database was analyzed. Western blotting and real -time quantitative polymerase chain reaction (RT-qPCR) were applied to detect LRFN4 expression in 8 groups of fresh gastric cancer tissues and adjacent normal tissues. Immunohistochemistry was used to detect LRFN4 expression in the gastric cancer tissue microarray. The differences in clinicopathological parameters of gastric cancer patients with different LRFN4 expression levels were analyzed. The prognosis of gastric cancer patients with different LRFN4 expression levels was analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were further conducted to identify factors affecting the prognosis of gastric cancer patients. Result  LRFN4 was highly expressed in gastric cancer tissues in both the TCGA dataset and fresh gastric cancer tissues. Patients with high expression of LRFN4 exhibited larger tumor size and more advanced T stage, N stage, M stage and TNM stage (all P＜0.05), and had poorer prognosis (P＜0.001). Univariate and multivariate Cox regression analyses indicated that high LRFN4 expression in gastric cancer tissues was an independent risk factor influencing the prognosis of gastric cancer patients (HR=3.898, 95%CI 2.273-6.686, P<0.001). Conclusion  High expression of LRFN4 in gastric cancer tissues is associated with poor prognosis in patients and may act as a novel potential biomarker for predicting the prognosis of gastric cancer patients.

Key Words:  Gastric cancer; Leucine -rich repeat and fibronectin type Ⅲdomain-containing protein 4; The cancer genome atlas; Biomarker; Prognosis of gastric cancer

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