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核糖体蛋白L19是一种预后生物标志物,并促进肝细胞癌的肿瘤进展。

RPL19 Is a Prognostic Biomarker and Promotes Tumor Progression in Hepatocellular Carcinoma.

作者信息

Rao Benchen, Li Jianhao, Ren Tong, Yang Jing, Zhang Guizhen, Liu Liwen, Wang Haiyu, Huang Maoxin, Ren Zhigang, Yu Zujiang

机构信息

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Precision Medicine Center, Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Cell Dev Biol. 2021 Jul 19;9:686547. doi: 10.3389/fcell.2021.686547. eCollection 2021.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most common malignancies, and the therapeutic outcome remains undesirable due to its recurrence and metastasis. Gene dysregulation plays a pivotal role in the occurrence and progression of cancer, and the molecular mechanisms are largely unknown.

METHODS

The differentially expressed genes of HCC screened from the GSE39791 dataset were used to conduct weighted gene co-expression network analysis. The selected hub genes were validated in The Cancer Genome Atlas (TCGA) database and 11 HCC datasets from the Gene Expression Omnibus (GEO) database. Then, a tissue microarray comprising 90 HCC specimens and 90 adjacent normal specimens was used to validate the hub genes. Moreover, the Hallmark, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify enriched pathways. Then, we conducted the immune infiltration analysis.

RESULTS

A total of 17 co-expression modules were obtained by weighted gene co-expression network analysis. The green, blue, and purple modules were the most relevant to HCC samples. Four hub genes, RPL19, RPL35A, RPL27A, and RPS12, were identified. Interestingly, we found that all four genes were highly expressed in HCC and that their high expression was related to a poor prognosis by analyzing the TCGA and GEO databases. Furthermore, we investigated RPL19 in HCC tissue microarrays and demonstrated that RPL19 was overexpressed in tumor tissues compared with non-tumor tissues ( = 0.016). Moreover, overexpression of RPL19 predicted a poor prognosis in hepatocellular carcinoma ( < 0.0007). Then, enrichment analysis revealed that cell cycle pathways were significantly enriched, and bile acid metabolism-related pathways were significantly down-regulated when RPL19 was highly expressed. Furthermore, immune infiltration analysis showed that immune response was suppressed.

CONCLUSION

Our study demonstrates that RPL19 may play an important role in promoting tumor progression and is correlated with a poor prognosis in HCC. RPL19 may serve as a promising biomarker and therapeutic target for the precise diagnosis and treatment of HCC in the future.

摘要

背景

肝细胞癌(HCC)是最常见的恶性肿瘤之一,由于其复发和转移,治疗效果仍然不理想。基因失调在癌症的发生和发展中起关键作用,但其分子机制 largely unknown。

方法

从GSE39791数据集中筛选出的HCC差异表达基因用于进行加权基因共表达网络分析。所选的枢纽基因在癌症基因组图谱(TCGA)数据库和来自基因表达综合数据库(GEO)的11个HCC数据集中进行验证。然后,使用包含90个HCC标本和90个相邻正常标本的组织微阵列来验证枢纽基因。此外,使用标志、基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库来识别富集途径。然后,我们进行了免疫浸润分析。

结果

通过加权基因共表达网络分析获得了总共17个共表达模块。绿色、蓝色和紫色模块与HCC样本最相关。鉴定出四个枢纽基因,即核糖体蛋白L19(RPL19)、核糖体蛋白L35A(RPL35A)、核糖体蛋白L27A(RPL27A)和核糖体蛋白S12(RPS12)。有趣的是,通过分析TCGA和GEO数据库,我们发现这四个基因在HCC中均高表达,且它们的高表达与预后不良相关。此外,我们在HCC组织微阵列中研究了RPL19,并证明与非肿瘤组织相比,RPL19在肿瘤组织中过表达( = 0.016)。此外,RPL19的过表达预示着肝细胞癌的预后不良( < 0.0007)。然后,富集分析显示,当RPL19高表达时,细胞周期途径显著富集,而胆汁酸代谢相关途径显著下调。此外,免疫浸润分析表明免疫反应受到抑制。

结论

我们的研究表明,RPL19可能在促进肿瘤进展中起重要作用,并且与HCC的预后不良相关。RPL19可能作为未来HCC精确诊断和治疗的有前景的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba5d/8327752/94bd3c539d25/fcell-09-686547-g001.jpg

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