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胃动素-2(GKN2)在肺癌和胃癌中的预后价值及其与肿瘤浸润免疫细胞的相关性

Prognostic Value of Gastrokine-2 (GKN2) and Its Correlation with Tumor-Infiltrating Immune Cells in Lung Cancer and Gastric Cancers.

作者信息

Liu Fangteng, Wu Hengyu

机构信息

Department of Breast Surgery, The Third Hospital of Nanchang, Nanchang, Jiangxi 330009, People's Republic of China.

Faculty of Medicine, University of Munich, Munich 80336, Germany.

出版信息

J Inflamm Res. 2020 Nov 16;13:933-944. doi: 10.2147/JIR.S277353. eCollection 2020.

Abstract

BACKGROUND

GKN2, as a secretory protein, is involved in the inflammation and immune modulation, and its aberrant expression is closely related to tumorigenesis. However, integrated studies on the value of GKN2 as a promising clinical biomarker and immunotherapy target in multiple tumors are still rare.

METHODOLOGY

Multiple online databases, including ONCOMINE, SEGreg, UALCAN, GEPIA, K-M Plotter, cBioPortal, MethSurv, CellMarker, and Timer, were applied to assess the clinical significance of GKN2 and its correlation with tumor-infiltrating immune cells in differentially expressed cancers.

RESULTS

Several databases confirmed that GKN2 was significantly down-regulated in lung and gastric cancers compared that in normal samples. GKN2 was altered in 3%, 5%, and 4% of the LUAD, LUSC, and STAD samples, respectively. Hyper-methylation of GKN2 was found in LUAD and LUSC samples. For the clinical values of GKN2, we found that the low transcription level of GKN2 was associated with worse OS in lung cancer, and inferior FP and PPS in gastric cancer, and the relationships between GKN2 expression and clinical variables regarding OS/FP/PPS in lung and gastric cancers were assessed. Moreover, the prognostic value of the DNA methylation patterns of GKN2 in LUAD, LUSC, and STAD was identified. Furthermore, GKN2 expression was found to be significantly correlated with the infiltrating multiple tumor immune cells, and statistically significant differences in the correlation between GKN2 expression and multiple markers of neutrophils and macrophage polarization were observed in LUAD, LUSC, and STAD.

CONCLUSION

The study revealed the prognosis and risk factors for deterioration in patients with low expression of GKN2. GKN2 may be used as a valuable prognostic biomarker and therapeutic target in lung and gastric cancers.

摘要

背景

GKN2作为一种分泌蛋白,参与炎症和免疫调节,其异常表达与肿瘤发生密切相关。然而,关于GKN2作为多种肿瘤中有前景的临床生物标志物和免疫治疗靶点价值的综合研究仍然很少。

方法

应用多个在线数据库,包括ONCOMINE、SEGreg、UALCAN、GEPIA、K-M Plotter、cBioPortal、MethSurv、CellMarker和Timer,评估GKN2在差异表达癌症中的临床意义及其与肿瘤浸润免疫细胞的相关性。

结果

多个数据库证实,与正常样本相比,GKN2在肺癌和胃癌中显著下调。GKN2在肺腺癌(LUAD)、肺鳞癌(LUSC)和胃腺癌(STAD)样本中的改变率分别为3%、5%和4%。在LUAD和LUSC样本中发现了GKN2的高甲基化。对于GKN2的临床价值,我们发现GKN2的低转录水平与肺癌患者较差的总生存期(OS)以及胃癌患者较差的无进展生存期(FP)和无进展生存期(PPS)相关,并评估了GKN2表达与肺癌和胃癌中OS/FP/PPS相关临床变量之间的关系。此外,还确定了GKN2的DNA甲基化模式在LUAD、LUSC和STAD中的预后价值。此外,发现GKN2表达与多种肿瘤免疫细胞浸润显著相关,并且在LUAD、LUSC和STAD中观察到GKN2表达与中性粒细胞和巨噬细胞极化的多种标志物之间的相关性存在统计学显著差异。

结论

该研究揭示了GKN2低表达患者的预后及病情恶化的危险因素。GKN2可能作为肺癌和胃癌中有价值的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1dd3/7678718/f88d6554101c/JIR-13-933-g0001.jpg

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