Transcriptome analysis reveals the link between lncRNA-mRNA co-expression network and tumor immune microenvironment and overall survival in head and neck squamous cell carcinoma
Transcriptome analysis reveals the link between lncRNA-mRNA co-expression network and tumor immune microenvironment and overall survival in head and neck squamous cell carcinoma
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转录组分析揭示了头颈鳞状细胞癌中lncRNA-mRNA共表达网络与肿瘤免疫微环境和总体生存率之间的联系
DOI：
10.1186/s12920-020-0707-0
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发表时间：
2020-03
影响因子：
2.7
通讯作者：
Liang Jin
中科院分区：
文献类型：
--
作者：
Zhong Zhaoming;Hong Min;Chen Xiao;Xi Yan;Xu Yuanyuan;Kong Deyu;Deng Jun;Li Yun;Hu Rui;Sun Chuanzheng;Liang Jin
背景作为全球第六大常见癌症，头颈鳞状细胞癌（HNSCC）在疾病晚期会发生内脏转移，五年生存率较低。肿瘤微环境（TME）在肿瘤发生和转移中的重要性已得到广泛认可。此外，越来越多的证据表明长链非编码RNA（lncRNA）参与TME和肿瘤细胞之间的串扰。然而，调节 HNSCC 微环境和进展的 lncRNA 相关调节因子仍然很大程度上未知。方法公开的转录组数据和匹配的临床 HNSCC 数据来自癌症基因组图谱 (TCGA)。使用 ESTIMATE 算法计算 HNSCC TME 的免疫评分 (IS) 和基质评分 (SS)。进行加权基因共表达网络分析（WGCNA）以确定共表达的lncRNA和蛋白质编码mRNA。结果结果显示，高IS HNSCC男性患者亚组表现出改善的生存率。此外，我们还鉴定出 169 个 lncRNA 和 825 个蛋白质编码 mRNA 在高 IS HNSCC 样本中差异表达，上调的 mRNA 在免疫相关生物过程中表现出富集。值得注意的是，我们发现了一个高共表达 lncRNA-mRNA 模块（即紫色模块），它与 IS 具有很强的相关性。该模块包含 79 个 lncRNA 和 442 个 mRNA，其中 26 个 lncRNA 和 215 个 mRNA 显示表达与男性 HNSCC 存活之间的关联。一致地，215 个 mRNA 中的 207 个在高 IS HNSCC 组中上调，并且在免疫相关信号通路中富集。基于生物信息学分析和之前的功能测定，紫色模块中的某些lncRNA（例如，AL365361.1和PCED1B-AS1）可能通过调节丰富的免疫相关基因（例如，CCR7和TLR8）的转录来改变高IS HNSCC患者的肿瘤免疫微环境（TIME）。结论总而言之，我们确定了表现出高IS的HNSCC男性患者亚组和良好的生存概率。我们在该 HNSCC 亚组中鉴定了数百个具有特定表达模式的基因，以及高度共表达的 lncRNA-mRNA 模块，该模块在调节 HNSCC 的 TIME 方面具有巨大潜力。我们的研究提供了 lncRNA 相关基因网络、TIME 和 HNSCC 进展之间联系的证据，并强调了这种疾病的潜在治疗靶点。
BackgroundAs the sixth most common cancer worldwide, head and neck squamous cell carcinoma (HNSCC) develops visceral metastases during the advanced stage of the disease and exhibits a low five-year survival rate. The importance of tumor microenvironment (TME) in tumor initiation and metastasis is widely recognized. In addition, accumulating evidence indicates that long non-coding RNA (lncRNA) is involved in crosstalk between TME and tumor cells. However, the lncRNA-associated regulators modulating the HNSCC microenvironment and progression remain largely unknown.MethodsThe publicly available transcriptome data and matched clinical HNSCC data were collected from The Cancer Genome Atlas (TCGA). Immune scores (ISs) and stromal scores (SSs) of HNSCC TME were calculated using ESTIMATE algorithm. Weighted gene co-expression network analysis (WGCNA) was conducted to determine the co-expressed lncRNAs and protein-coding mRNAs.ResultsResults showed that the high IS HNSCC male patient subgroup exhibited improved survival. Additionally, we identified 169 lncRNAs and 825 protein-coding mRNAs that were differentially expressed in high IS HNSCC samples, with the up-regulated mRNAs displaying enrichment in immune-related biological processes. Notably, we identified a high co-expression lncRNA-mRNA module (i.e., purple module) that showed strong correlation with ISs. This module contained 79 lncRNAs and 442 mRNAs, including 26 lncRNAs and 215 mRNAs showing association between expression and male HNSCC survival. Consistently, 207 of the 215 mRNAs were up-regulated in high IS HNSCC group and were enriched in immune-related signaling pathways. Based on bioinformatics analyses and previous functional assays, certain lncRNAs (e.g.,AL365361.1andPCED1B-AS1) in the purple module likely contributed to the modification of tumor immune microenvironment (TIME) in the high IS HNSCC patients, achieved by regulating transcription of abundant immune-related genes (e.g.,CCR7andTLR8).ConclusionsIn summary, we ascertained a HNSCC male patient subgroup that displayed high ISs and good survival probability. We identified hundreds of genes with specific expression patterns in this HNSCC subgroup as well as a highly co-expressed lncRNA-mRNA module with great potential for the modulation of TIME of HNSCC. Our study provides evidence of a link between the lncRNA-associated gene network, TIME, and HNSCC progression, and highlights potential therapeutic targets for this disease.
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影响因子：
3.8
作者：
Lu KH;Li W;Liu XH;Sun M;Zhang ML;Wu WQ;Xie WP;Hou YY
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影响因子：
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DOI：
10.1038/nrc.2017.99
发表时间：
2018-01
期刊：
Nature reviews. Cancer
影响因子：
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作者：
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通讯作者：
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影响因子：
3.3
作者：
Mao Y;Feng Q;Zheng P;Yang L;Liu T;Xu Y;Zhu D;Chang W;Ji M;Ren L;Wei Y;He G;Xu J
通讯作者：
Xu J
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影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S