Department of Medical Oncology, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.
Department of Head and Neck Surgery Section II, Third Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.
BMC Med Genomics. 2020 Mar 30;13(1):57. doi: 10.1186/s12920-020-0707-0.
As 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.
The 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.
Results 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., AL365361.1 and PCED1B-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., CCR7 and TLR8).
In 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.
作为全球第六大常见癌症，头颈部鳞状细胞癌（HNSCC）在疾病的晚期发展为内脏转移，并表现出五年生存率低的特点。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，长非编码 RNA（lncRNA）参与了 TME 与肿瘤细胞之间的串扰。然而，调节 HNSCC 微环境和进展的 lncRNA 相关调节剂在很大程度上仍然未知。
从癌症基因组图谱（TCGA）中收集了公开的转录组数据和匹配的 HNSCC 临床数据。使用 ESTIMATE 算法计算 HNSCC TME 的免疫评分（ISs）和基质评分（SSs）。进行加权基因共表达网络分析（WGCNA）以确定共表达的 lncRNA 和蛋白编码 mRNA。
结果表明，高 IS HNSCC 男性患者亚组的生存情况得到改善。此外，我们鉴定了 169 个在高 IS HNSCC 样本中差异表达的 lncRNA 和 825 个蛋白编码 mRNA，上调的 mRNAs 在免疫相关的生物学过程中富集。值得注意的是，我们鉴定了一个与 ISs 强烈相关的高共表达 lncRNA-mRNA 模块（即紫色模块）。该模块包含 79 个 lncRNA 和 442 个 mRNA，其中 26 个 lncRNA 和 215 个 mRNA 的表达与男性 HNSCC 生存相关。一致地，在高 IS HNSCC 组中，215 个 mRNA 中有 207 个上调，并且富集在免疫相关信号通路中。基于生物信息学分析和先前的功能测定，紫色模块中的某些 lncRNA（例如 AL365361.1 和 PCED1B-AS1）可能通过调节大量免疫相关基因（例如 CCR7 和 TLR8）的转录，从而在高 IS HNSCC 患者中对肿瘤免疫微环境（TIME）的修饰做出贡献。
总之，我们确定了一个具有高 IS 和良好生存概率的 HNSCC 男性患者亚组。我们鉴定了该 HNSCC 亚组中具有特定表达模式的数百个基因，以及一个具有很大潜力可调节 HNSCC 的 TIME 的高度共表达 lncRNA-mRNA 模块。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，并强调了该疾病的潜在治疗靶点。
