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基于 RNA 测序数据鉴定 12 个免疫相关长链非编码 RNA 并对透明细胞肾细胞癌进行分子亚型分类。

Identification of 12 immune-related lncRNAs and molecular subtypes for the clear cell renal cell carcinoma based on RNA sequencing data.

机构信息

The Fifth Hospital of Xiamen, Xiamen, 361101, Fujian Province, People's Republic of China.

The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, 361003, Fujian Province, People's Republic of China.

出版信息

Sci Rep. 2020 Sep 2;10(1):14412. doi: 10.1038/s41598-020-71150-3.

DOI:10.1038/s41598-020-71150-3
PMID:32879362
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7467926/
Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma (RCC). Despite the existing extensive research, the molecular and pathogenic mechanisms of ccRCC are elusive. We aimed to identify the immune-related lncRNA signature and molecular subtypes associated with ccRCC. By integrating 4 microarray datasets from Gene Expression Omnibus database, we identified 49 immune-related genes. The corresponding immune-related lncRNAs were further identified in the TCGA dataset. 12-lncRNAs prognostic and independent signature was identified through survival analysis and survival difference between risk groups was further identified based on the risk score. Besides, we identified 3 molecular subtypes and survival analysis result showed that cluster 2 has a better survival outcome. Further, ssGSEA enrichment analysis for the immune-associated gene sets revealed that cluster 1 corresponded to a high immune infiltration level. While cluster 2 and cluster 3 corresponded to low and medium immune infiltration level, respectively. In addition, we validated the 12-lncRNA prognostic signature and molecular subtypes in an external validation dataset from the ICGC database. In summary, we identified a 12-lncRNA prognostic signature which may provide new insights into the molecular mechanisms of ccRCC and the molecular subtypes provided a theoretical basis for personalized treatment by clinicians.

摘要

透明细胞肾细胞癌 (ccRCC) 是最常见的肾细胞癌 (RCC) 类型。尽管已经进行了广泛的研究,但 ccRCC 的分子和发病机制仍不清楚。我们旨在确定与 ccRCC 相关的免疫相关 lncRNA 特征和分子亚型。通过整合来自基因表达综合数据库的 4 个微数组数据集,我们鉴定了 49 个免疫相关基因。在 TCGA 数据集中进一步鉴定了相应的免疫相关 lncRNA。通过生存分析确定了 12-lncRNA 预后和独立特征,并根据风险评分进一步确定了风险组之间的生存差异。此外,我们还鉴定了 3 个分子亚型,生存分析结果表明,簇 2 具有更好的生存结果。进一步的 ssGSEA 免疫相关基因集富集分析表明,簇 1 对应于高免疫浸润水平。而簇 2 和簇 3 分别对应于低和中等免疫浸润水平。此外,我们在来自 ICGC 数据库的外部验证数据集中验证了 12-lncRNA 预后特征和分子亚型。总之,我们确定了一个 12-lncRNA 预后特征,它可能为 ccRCC 的分子机制提供新的见解,而分子亚型为临床医生提供了个性化治疗的理论基础。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e4/7467926/82be0ff9fdb5/41598_2020_71150_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e4/7467926/31fb23bf8c69/41598_2020_71150_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e4/7467926/edefd117f93e/41598_2020_71150_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e4/7467926/496cac99b252/41598_2020_71150_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e4/7467926/f2d57e29b655/41598_2020_71150_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e4/7467926/ca67243c36f8/41598_2020_71150_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e4/7467926/5859535af83a/41598_2020_71150_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e4/7467926/cad4bcae1217/41598_2020_71150_Fig11_HTML.jpg

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