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LINC01094 预测胃癌患者预后不良,并与 EMT 和巨噬细胞浸润相关。

LINC01094 Predicts Poor Prognosis in Patients With Gastric Cancer and is Correlated With EMT and Macrophage Infiltration.

机构信息

117894Department of Gastroenterology, Quanzhou First Hospital affiliated to Fujian Medical University, Quanzhou, Fujian Province, People's Republic of China.

Department of Hematology Oncology and Tumor Immunity, Benjamin Franklin Campus, 14903Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

出版信息

Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221080977. doi: 10.1177/15330338221080977.

Abstract

The novel long non-coding RNA (lncRNA) LINC01094 is often upregulated in renal cell carcinoma and glioma; however, its role in gastric cancer remains unclear. Here, we aim to demonstrate the relationship between LINC01094 and gastric cancer. The gene expression (RNASeq) data of 375 patients with localized, locally advanced, and metastatic gastric cancer were extracted from The Cancer Genome Atlas. The Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to analyze the relationship between the clinicopathological characteristics and LINC01094 expression. Cox regression analysis and the Kaplan-Meier method were used to assess prognostic factors of gastric cancer. A nomogram based on Cox multivariate analysis was used to predict the impact of LINC01094 on gastric cancer prognosis. Gene set enrichment analysis (GSEA) was used to identify key LINC01094-associated signaling pathways. Fluorescence in situ hybridization (FISH) was performed to detect the location of LINC01094 in the tissue, and a competing endogenous (ce)RNA network was constructed to identify LINC01094-related genes. Spearman's rank correlation was used to elucidate the association between LINC01094 expression level and immune cell infiltration level. LINC01094 expression was upregulated in gastric cancer tissues and strongly associated with overall survival using univariate Cox regression (hazard ratio [HR]  =  1.476, 95% CI  =  1.060-2.054,   =  .021) and multivariate Cox regression analysis (HR  =  1.535, 95% CI  =  1.021-2.308,   =  .039). The area under the receiver operating characteristic curve of LINC01094 was 0.910. GSEA showed a strong relationship between LINC01094 and the epithelial-mesenchymal transition pathway. RNA-FISH demonstrated that LINC01094 localized in the cytoplasm. It was closely related to the epithelial-mesenchymal transition (EMT) marker , according to ceRNA (  =  0.61,  < .001), and macrophage-related gene . Macrophages were also significantly positively correlated with LINC01094 expression (  =  0.747,  < .001). High LINC01094 expression predicts poor prognosis in gastric cancer and is correlated with the epithelial-mesenchymal transition pathway and macrophage infiltration.

摘要

新型长链非编码 RNA (lncRNA) LINC01094 在肾细胞癌和神经胶质瘤中常上调;然而,其在胃癌中的作用尚不清楚。在这里,我们旨在证明 LINC01094 与胃癌之间的关系。从癌症基因组图谱中提取了 375 名局限性、局部晚期和转移性胃癌患者的基因表达(RNAseq)数据。采用 Kruskal-Wallis 检验、Wilcoxon 符号秩检验和逻辑回归分析 LINC01094 表达与临床病理特征的关系。Cox 回归分析和 Kaplan-Meier 法用于评估胃癌的预后因素。基于 Cox 多因素分析的列线图用于预测 LINC01094 对胃癌预后的影响。基因集富集分析(GSEA)用于鉴定与 LINC01094 相关的关键信号通路。荧光原位杂交(FISH)用于检测组织中 LINC01094 的位置,并构建竞争内源性(ce)RNA 网络以鉴定 LINC01094 相关基因。Spearman 秩相关用于阐明 LINC01094 表达水平与免疫细胞浸润水平之间的关联。LINC01094 在胃癌组织中表达上调,单因素 Cox 回归(危险比[HR]  =  1.476,95%CI  =  1.060-2.054,p=0.021)和多因素 Cox 回归分析(HR  =  1.535,95%CI  =  1.021-2.308,p=0.039)均强烈提示与总体生存相关。LINC01094 的受试者工作特征曲线下面积为 0.910。GSEA 显示 LINC01094 与上皮-间充质转化途径之间存在很强的关系。RNA-FISH 表明 LINC01094 定位于细胞质中。它与上皮-间充质转化(EMT)标志物紧密相关,根据 ceRNA(  =  0.61,p<0.001)和巨噬细胞相关基因(  =  0.21,p<0.001)。巨噬细胞也与 LINC01094 表达呈显著正相关(  =  0.747,p<0.001)。高 LINC01094 表达预测胃癌预后不良,与上皮-间充质转化途径和巨噬细胞浸润相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a90/8905065/d4df5acd756a/10.1177_15330338221080977-fig1.jpg

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