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基于 WGCNA 枢纽基因筛选策略的肝癌关键预后相关原癌基因 FYN 的新发现。

A new finding in the key prognosis-related proto-oncogene FYN in hepatocellular carcinoma based on the WGCNA hub-gene screening trategy.

机构信息

Department of Digestive Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

出版信息

BMC Cancer. 2022 Apr 9;22(1):380. doi: 10.1186/s12885-022-09388-5.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the third-most deadly cancer worldwide. More breakthroughs are needed in the clinical practice for liver cancer are needed, and new treatment strategies are required. This study aims to determine the significant differences in genes associated with LIHC and further analyze its prognostic value further.

METHODS

Here, we used the TCGA-LIHC database and the profiles of GSE25097 from GEO to explore the differentially co-expressed genes in HCC tissues compared with paratumor (or healthy) tissues. Then, we utilized WGCNA to screen differentially co-expressed genes. Finally, we explored the function of FYN in HCC cells and xenograft tumor models.

RESULTS

We identified ten hub genes in the protein-protein interaction (PPI) network, but only three (COLEC10, TGFBR3, and FYN) appeared closely related to the prognosis. The expression of FYN was positively correlated with the prognosis of HCC patients. The xenograft model showed that overexpression of FYN could significantly inhibit malignant tumor behaviors and promote tumor cell apoptosis.

CONCLUSION

Thus, FYN may be central to the development of LIHC and maybe a novel biomarker for clinical diagnosis and treatment.

摘要

背景

肝细胞癌(HCC)是全球致死率第三高的癌症。肝癌的临床实践需要更多突破,需要新的治疗策略。本研究旨在确定与 LIHC 相关的基因的显著差异,并进一步分析其预后价值。

方法

在这里,我们使用 TCGA-LIHC 数据库和 GEO 中的 GSE25097 谱来比较 HCC 组织与肿瘤旁(或健康)组织中差异共表达的基因。然后,我们利用 WGCNA 筛选差异共表达基因。最后,我们探索了 FYN 在 HCC 细胞和异种移植肿瘤模型中的功能。

结果

我们在蛋白质-蛋白质相互作用(PPI)网络中确定了十个枢纽基因,但只有三个(COLEC10、TGFBR3 和 FYN)与预后密切相关。FYN 的表达与 HCC 患者的预后呈正相关。异种移植模型表明,FYN 的过表达可显著抑制恶性肿瘤行为并促进肿瘤细胞凋亡。

结论

因此,FYN 可能是 LIHC 发展的核心,也可能是临床诊断和治疗的新生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d157/8994319/97ee111709b9/12885_2022_9388_Fig1_HTML.jpg

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