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生物信息学分析表明,组织蛋白酶G(CTSG)是口腔鳞状细胞癌(OSCC)中一种潜在的免疫相关生物标志物。

Bioinformatics Analyses Indicate That Cathepsin G (CTSG) is a Potential Immune-Related Biomarker in Oral Squamous Cell Carcinoma (OSCC).

作者信息

Huang Guang-Zhao, Wu Qing-Qing, Zheng Ze-Nan, Shao Ting-Ru, Li Fei, Lu Xin-Yan, Ye Heng-Yu, Chen Gao-Xiang, Song Yu-Xing, Zeng Wei-Sen, Ai Yi-Long, Lv Xiao-Zhi

机构信息

Department of Oral & Maxillofacial Surgery, NanFang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.

Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.

出版信息

Onco Targets Ther. 2021 Feb 25;14:1275-1289. doi: 10.2147/OTT.S293148. eCollection 2021.

Abstract

PURPOSE

Plenty of studies showed that the immune system was associated with cancer initiation and progression. This study aimed to explore the prognostic biomarkers from immune-related genes (IRGs) in oral squamous cell carcinoma (OSCC).

MATERIALS AND METHODS

RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and IRGs and transcription factors (TFs) were extracted. Then, the co-expression network between IRGs and TFs was constructed using the "WGCNA" package in R software. Furthermore, a gene expression signature according to IRGs was constructed to predict OSCC prognosis and its accuracy was validated by survival analysis. Subsequently, correlation analyses between risk-score and immune cells level and clinical parameters were performed. Finally, immune-related biomarkers were selected and further investigated using gain-of-function assays in vitro.

RESULTS

A total of 32 normal cases and 317 OSCC cases were selected in our study. Differentially-expressed analysis indicated that there were 381 differentially-expressed IRGs and 62 TFs in OSCC. Among them, 25 TFs and 21 IRGs were enrolled in the co-expression network. Furthermore, we found that gene expression signature on the basis of 10 IRGs could predict the prognosis accurately and a high-risk score based on gene expression signature meant a high T classification, terminal clinical stage, and low immune cells level in OSCC. Finally, cathepsin G (CTSG) was identified as a potential immune-related biomarker and therapeutic target in OSCC.

CONCLUSION

In conclusion, IRGs were directly involved in the development and progression of OSCC. Furthermore, CTSG was identified as a potential independent biomarker and might be an immunotherapeutic target in OSCC treatment.

摘要

目的

大量研究表明免疫系统与癌症的发生和发展相关。本研究旨在探索口腔鳞状细胞癌(OSCC)中免疫相关基因(IRG)的预后生物标志物。

材料与方法

从癌症基因组图谱(TCGA)下载RNA测序数据,并提取IRG和转录因子(TF)。然后,使用R软件中的“WGCNA”包构建IRG与TF之间的共表达网络。此外,构建基于IRG的基因表达特征以预测OSCC的预后,并通过生存分析验证其准确性。随后,进行风险评分与免疫细胞水平及临床参数之间的相关性分析。最后,选择免疫相关生物标志物并在体外进行功能获得性试验进一步研究。

结果

本研究共纳入32例正常病例和317例OSCC病例。差异表达分析表明,OSCC中有381个差异表达的IRG和62个TF。其中,25个TF和21个IRG纳入共表达网络。此外,我们发现基于10个IRG的基因表达特征能够准确预测预后,基于基因表达特征的高风险评分意味着OSCC中T分级高、临床终末期以及免疫细胞水平低。最后,组织蛋白酶G(CTSG)被确定为OSCC中潜在的免疫相关生物标志物和治疗靶点。

结论

总之,IRG直接参与OSCC的发生和发展。此外,CTSG被确定为潜在的独立生物标志物,可能是OSCC治疗中的免疫治疗靶点。

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