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鉴定和验证与 m7G 相关的 lncRNA 特征,以预测肝细胞癌的预后和治疗反应。

Identification and validation of a m7G-related lncRNA signature for predicting the prognosis and therapy response in hepatocellular carcinoma.

机构信息

Department of Nephrology, Shanxi Provincial People's Hospital (Fifth Hospital of Shanxi Medical University), Taiyuan, China.

Department of Pathology and Pathophysiology, School of Basic Medicine, Shanxi Medical University, Taiyuan, China.

出版信息

PLoS One. 2023 Aug 3;18(8):e0289552. doi: 10.1371/journal.pone.0289552. eCollection 2023.

Abstract

BACKGROUND

N7-methylguanosine (m7G) is one of the most common RNA posttranscriptional modifications; however, its potential role in hepatocellular carcinoma (HCC) remains unknown. We developed a prediction signature based on m7G-related long noncoding RNAs (lncRNAs) to predict HCC prognosis and provide a reference for immunotherapy and chemotherapy.

METHODS

RNA-seq data from The Cancer Genome Atlas (TCGA) database and relevant clinical data were used. Univariate and multivariate Cox regression analyses were conducted to identify m7G-related lncRNAs with prognostic value to build a predictive signature. We evaluated the prognostic value and clinical relevance of this signature and explored the correlation between the predictive signature and the chemotherapy treatment response of HCC. Moreover, an in vitro study to validate the function of CASC19 was performed.

RESULTS

Six m7G-related lncRNAs were identified to create a signature. This signature was considered an independent risk factor for the prognosis of patients with HCC. TIDE analyses showed that the high-risk group might be more sensitive to immunotherapy. ssGSEA indicated that the predictive signature was strongly related to the immune activities of HCC. HCC in high-risk patients was more sensitive to the common chemotherapy drugs bleomycin, doxorubicin, gemcitabine, and lenalidomide. In vitro knockdown of CASC19 inhibited the proliferation, migration and invasion of HCC cells.

CONCLUSION

We established a 6 m7G-related lncRNA signature that may assist in predicting the prognosis and response to chemotherapy and immunotherapy of HCC.

摘要

背景

N7-甲基鸟苷(m7G)是最常见的 RNA 转录后修饰之一;然而,其在肝细胞癌(HCC)中的潜在作用尚不清楚。我们开发了一个基于 m7G 相关长非编码 RNA(lncRNA)的预测特征,以预测 HCC 的预后,并为免疫治疗和化疗提供参考。

方法

使用来自癌症基因组图谱(TCGA)数据库的 RNA-seq 数据和相关临床数据。进行单变量和多变量 Cox 回归分析,以确定具有预后价值的 m7G 相关 lncRNA,从而构建预测特征。我们评估了该特征的预后价值和临床相关性,并探讨了预测特征与 HCC 化疗治疗反应之间的相关性。此外,还进行了体外研究来验证 CASC19 的功能。

结果

确定了 6 个 m7G 相关 lncRNA 来创建特征。该特征被认为是 HCC 患者预后的独立危险因素。TIDE 分析表明,高危组可能对免疫治疗更敏感。ssGSEA 表明,预测特征与 HCC 的免疫活性密切相关。高危患者的 HCC 对常见化疗药物博来霉素、多柔比星、吉西他滨和来那度胺更敏感。体外敲低 CASC19 抑制了 HCC 细胞的增殖、迁移和侵袭。

结论

我们建立了一个 6 个 m7G 相关 lncRNA 特征,可用于预测 HCC 的预后和对化疗和免疫治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee53/10399872/31c82d3edc17/pone.0289552.g001.jpg

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