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构建新型免疫相关 lncRNA 标志物,并预测其预测肝细胞癌患者免疫状态的潜力。

Construction of a novel immune-related lncRNA signature and its potential to predict the immune status of patients with hepatocellular carcinoma.

机构信息

Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.

State Key Laboratory of Oncology in South China, Guangzhou, China.

出版信息

BMC Cancer. 2021 Dec 19;21(1):1347. doi: 10.1186/s12885-021-09059-x.

Abstract

BACKGROUND

The accuracy of existing biomarkers for predicting the prognosis of hepatocellular carcinoma (HCC) is not satisfactory. It is necessary to explore biomarkers that can accurately predict the prognosis of HCC.

METHODS

In this study, original transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. Immune-related long noncoding ribonucleic acids (irlncRNAs) were identified by coexpression analysis, and differentially expressed irlncRNA (DEirlncRNA) pairs were distinguished by univariate analysis. In addition, the least absolute shrinkage and selection operator (LASSO) penalized regression was modified. Next, the cutoff point was determined based on the area under the curve (AUC) and Akaike information criterion (AIC) values of the 5-year receiver operating characteristic (ROC) curve to establish an optimal model for identifying high-risk and low-risk groups of HCC patients. The model was then reassessed in terms of clinicopathological features, survival rate, tumor-infiltrating immune cells, immunosuppressive markers, and chemotherapy efficacy.

RESULTS

A total of 1009 pairs of DEirlncRNAs were recognized in this study, 30 of these pairs were included in the Cox regression model for subsequent analysis. After regrouping according to the cutoff point, we could more effectively identify factors such as aggressive clinicopathological features, poor survival outcomes, specific immune cell infiltration status of tumors, high expression level of immunosuppressive biomarkers, and low sensitivity to chemotherapy drugs in HCC patients.

CONCLUSIONS

The nonspecific expression level signature involved with irlncRNAs shows promising clinical value in predicting the prognosis of HCC patients.

摘要

背景

现有的用于预测肝细胞癌 (HCC) 预后的生物标志物的准确性并不令人满意。有必要探索能够准确预测 HCC 预后的生物标志物。

方法

本研究从癌症基因组图谱 (TCGA) 数据库中下载了原始转录组数据。通过共表达分析鉴定免疫相关长非编码 RNA (irlncRNA),并通过单变量分析区分差异表达的irlncRNA (DEirlncRNA) 对。此外,还修改了最小绝对值收缩和选择算子 (LASSO) 惩罚回归。然后,根据 5 年接收者操作特征 (ROC) 曲线的 AUC 和 AIC 值确定截断点,以建立一个用于识别 HCC 患者高风险和低风险组的最优模型。然后,根据临床病理特征、生存率、肿瘤浸润免疫细胞、免疫抑制标志物和化疗疗效对该模型进行重新评估。

结果

本研究共鉴定出 1009 对 DEirlncRNA,其中 30 对被纳入 Cox 回归模型进行后续分析。根据截断点重新分组后,我们可以更有效地识别 HCC 患者侵袭性临床病理特征、较差的生存结局、肿瘤特定免疫细胞浸润状态、高表达水平的免疫抑制标志物以及对化疗药物低敏感性等因素。

结论

涉及 irlncRNA 的非特异性表达水平特征在预测 HCC 患者预后方面具有有前景的临床价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68ec/8684648/5e4be0e52313/12885_2021_9059_Fig1_HTML.jpg

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