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胃腺癌中长链非编码RNA的表达模式可作为肿瘤突变负荷的指标,并与肿瘤浸润淋巴细胞和微卫星不稳定性相关。

Long Non-coding RNA Expression Patterns in Stomach Adenocarcinoma Serve as an Indicator of Tumor Mutation Burden and Are Associated With Tumor-Infiltrating Lymphocytes and Microsatellite Instability.

作者信息

Yang Dongdong, Yu Jinling, Han Bing, Sun Yue, Mo Steven, Hu Jing

机构信息

Department of Surgical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of General Practice, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Cell Dev Biol. 2021 Feb 12;9:618313. doi: 10.3389/fcell.2021.618313. eCollection 2021.

DOI:10.3389/fcell.2021.618313
PMID:33644056
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7907456/
Abstract

Long non-coding RNAs (lncRNAs) are crucial in controlling important aspects of tumor immunity. However, whether the expression pattern of lncRNAs in stomach adenocarcinoma (STAD) reflects tumor immunity is not fully understood. We screened differentially expressed lncRNAs (DElncRNAs) between high and low tumor mutation burden (TMB) STAD samples. Using the least absolute shrinkage and selection operator method, 33 DElncRNAs were chosen to establish a lncRNA-based signature classifier for predicting TMB levels. The accuracy of the 33-lncRNA-based signature classifier was 0.970 in the training set and 0.950 in the test set, suggesting the expression patterns of the 33 lncRNAs may be an indicator of TMB in STAD. Survival analysis showed that a lower classifier index reflected better prognosis for STAD patients, and the index showed correlation with expression of immune checkpoint molecules (PD1, PDL1, and CTLA4), tumor-infiltrating lymphocytes, and microsatellite instability. In conclusion, STAD samples with different tumor mutation burdens have different lncRNA expression patterns. The 33-lncRNA-based signature classifier index may be an indicator of TMB and is associated expression of immune checkpoints, tumor-infiltrating lymphocytes, and microsatellite instability.

摘要

长链非编码RNA(lncRNAs)在控制肿瘤免疫的重要方面起着关键作用。然而,lncRNAs在胃腺癌(STAD)中的表达模式是否反映肿瘤免疫尚未完全明确。我们筛选了高肿瘤突变负担(TMB)和低肿瘤突变负担的STAD样本之间差异表达的lncRNAs(DElncRNAs)。使用最小绝对收缩和选择算子方法,选择了33个DElncRNAs来建立基于lncRNA的特征分类器以预测TMB水平。基于33个lncRNA的特征分类器在训练集中的准确率为0.970,在测试集中为0.950,这表明这33个lncRNAs的表达模式可能是STAD中TMB的一个指标。生存分析表明,较低的分类器指数反映STAD患者的预后较好,并且该指数与免疫检查点分子(PD1、PDL1和CTLA4)的表达、肿瘤浸润淋巴细胞以及微卫星不稳定性相关。总之,具有不同肿瘤突变负担的STAD样本具有不同的lncRNA表达模式。基于33个lncRNA的特征分类器指数可能是TMB的一个指标,并且与免疫检查点、肿瘤浸润淋巴细胞的表达以及微卫星不稳定性相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/1510b2bf2abb/fcell-09-618313-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/6b3df1b7231c/fcell-09-618313-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/deb7465f49e9/fcell-09-618313-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/99096c553e1e/fcell-09-618313-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/0982f4fd4d78/fcell-09-618313-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/080be1765f92/fcell-09-618313-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/1510b2bf2abb/fcell-09-618313-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/6b3df1b7231c/fcell-09-618313-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/deb7465f49e9/fcell-09-618313-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/99096c553e1e/fcell-09-618313-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/0982f4fd4d78/fcell-09-618313-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/080be1765f92/fcell-09-618313-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/483b/7907456/1510b2bf2abb/fcell-09-618313-g006.jpg

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