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LHFPL四跨膜蛋白亚家族成员6在胃癌中的预后价值:一项基于生物信息学分析和实验验证的研究

Prognostic Value of LHFPL Tetraspan Subfamily Member 6 in Gastric Cancer: A Study Based on Bioinformatics Analysis and Experimental Validation.

作者信息

Liu Yuan-Jie, Yin Sheng-Yan, Zeng Shu-Hong, Hu Yi-Dou, Wang Meng-Qi, Huang Pan, Li Jie-Pin

机构信息

Department of Oncology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People's Republic of China.

Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, People's Republic of China.

出版信息

Pharmgenomics Pers Med. 2021 Nov 20;14:1483-1504. doi: 10.2147/PGPM.S332345. eCollection 2021.

Abstract

PURPOSE

The identification of biomarkers and effective therapeutic targets for gastric cancer (GC), the most common cause of cancer-related deaths around the world, is currently a major focus in research. Here, we examined the utility of LHFPL6 as a prognostic biomarker and therapeutic target for GC.

METHODS

We explored the clinical relevance, function, and molecular role of LHFPL6 in GC using the MethSurv, cBioPortal, TIMER, Gene Expression Profiling Interactive Analysis, ONCOMINE, MEXPRESS, and EWAS Atlas databases. The GSE118919, GSE29272, and GSE13861 datasets were used for differential expression analysis. Using The Cancer Genome Atlas, we developed a Cox regression model and assessed the clinical significance of LHFPLs. In addition, we used the "CIBERSORT" algorithm to make reliable immune infiltration estimations. Western blot and immunohistochemistry were used to examine protein expression. Cell migration and invasion were assessed using transwell experiments. THP-1-derived macrophages and GC cells were co-cultured in order to model tumor-macrophage interactions in vitro. The levels of CD206 and CD163 were measured using immunofluorescence assays. The results were visualized with the "ggplot2" and "circlize" packages.

RESULTS

Our results showed that in GC, LHFPL6 overexpression was significantly associated with a poor prognosis. Our findings also suggested that LHFPL6 may be involved in the activation of the epithelial-mesenchymal transition. Furthermore, LHFPL6 expression showed a positive correlation with the abundance of M2 macrophages, which are potent immunosuppressors.

CONCLUSION

LHFPL6 could be a prognostic biomarker and therapeutic target for GC.

摘要

目的

胃癌是全球癌症相关死亡的最常见原因,鉴定其生物标志物和有效治疗靶点是当前研究的主要重点。在此,我们研究了LHFPL6作为胃癌预后生物标志物和治疗靶点的效用。

方法

我们使用MethSurv、cBioPortal、TIMER、基因表达谱交互分析、ONCOMINE、MEXPRESS和EWAS图谱数据库,探讨LHFPL6在胃癌中的临床相关性、功能和分子作用。使用GSE118919、GSE29272和GSE13861数据集进行差异表达分析。利用癌症基因组图谱,我们建立了Cox回归模型并评估了LHFPLs的临床意义。此外,我们使用“CIBERSORT”算法进行可靠的免疫浸润估计。采用蛋白质免疫印迹法和免疫组织化学法检测蛋白质表达。通过Transwell实验评估细胞迁移和侵袭能力。将THP-1来源的巨噬细胞与胃癌细胞共培养,以模拟体外肿瘤-巨噬细胞相互作用。采用免疫荧光法检测CD206和CD163水平。结果用“ggplot2”和“circlize”软件包进行可视化展示。

结果

我们的结果表明,在胃癌中,LHFPL6过表达与预后不良显著相关。我们的研究结果还表明,LHFPL6可能参与上皮-间质转化的激活。此外,LHFPL6表达与强效免疫抑制剂M2巨噬细胞的丰度呈正相关。

结论

LHFPL6可能是胃癌的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c541/8612673/0b63dd4b2882/PGPM-14-1483-g0001.jpg

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