Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
Cell Signal. 2023 Dec;112:110903. doi: 10.1016/j.cellsig.2023.110903. Epub 2023 Oct 7.
Both lipid metabolism reprogramming and lncRNAs exert effects on tumor development. We aimed to predict the prognosis of head and neck squamous cell carcinoma (HNSCC) based on lipid metabolism-related (LR)-lncRNAs.
LR-lncRNAs were determined from the RNA-ref profiles of HNSCC samples in The Cancer Genome Atlas (TCGA). The prognostic model was established by univariate Cox and Lasso regression analysis. Clinical relevance and predictive accuracy were investigated, and external validation was also performed in the Gene Expression Omnibus (GEO) cohort. Tumor immune infiltration and relevant functional analysis, including the association of autophagy with prognostic signatures, were conducted through single-sample gene set enrichment analysis (ssGSEA). The regulatory network of candidate LR-lncRNAs was investigated via coexpression, ceRNA and cis/trans acting interactions. Potential genes were selected through qRT-PCR analysis, and their effects on tumor biological activities and autophagic activity were explored after gene knockdown.
A total of 222 LR-lncRNAs were identified. Among the 41 genes with prognostic significance, 17 lncRNAs were eligible for the risk model. Patients in the high-risk group had a poorer prognosis than those in the low-risk group, and the risk score was found to be positively associated with tumor microenvironment infiltration via multiple algorithms. Furthermore, improved prognosis was found in patients with high autophagic scores and low risk scores, and autophagy-related genes such as PINK1 and CCL2 showed significantly lower expression in the low-risk group. The expression of immune checkpoint genes such as CD28, CTLA4 and PDCD1 decreased dramatically in the high-risk group. The target genes of candidate lncRNAs were confirmed, such as ENO2 and PPAR-gamma. Furthermore, MIR4435-2HG was the most significantly overexpressed lncRNA in HNSCC cell lines and tumor samples, which could promote proliferation and migration and inhibit apoptosis. Additionally, MIR4435-2HG silencing activated autophagy by increasing LC3B expression.
This study constructed an LR-lncRNA prognostic signature for HNSCC and indicated its relationships with tumor immunity and autophagy, which provides a promising future for LR-lncRNA-oriented prognostic tools and therapeutic targets.
脂质代谢重编程和长链非编码 RNA（lncRNA）都对肿瘤的发展产生影响。我们旨在基于脂质代谢相关（LR）-lncRNA 预测头颈部鳞状细胞癌（HNSCC）的预后。
从癌症基因组图谱（TCGA）的 HNSCC 样本的 RNA-seq 数据中确定 LR-lncRNA。通过单因素 Cox 和 Lasso 回归分析建立预后模型。进行临床相关性和预测准确性的研究，并在基因表达综合数据库（GEO）队列中进行外部验证。通过单样本基因集富集分析（ssGSEA）进行肿瘤免疫浸润和相关功能分析，包括自噬与预后特征的关联。通过共表达、ceRNA 和顺式/反式作用相互作用研究候选 LR-lncRNA 的调控网络。通过 qRT-PCR 分析选择潜在基因，并在基因敲低后探索其对肿瘤生物学活性和自噬活性的影响。
共鉴定出 222 个 LR-lncRNA。在具有预后意义的 41 个基因中，有 17 个 lncRNA 适合风险模型。高危组患者的预后比低危组差，风险评分通过多种算法发现与肿瘤微环境浸润呈正相关。此外，高自噬评分和低风险评分的患者预后改善，自噬相关基因如 PINK1 和 CCL2 在低风险组中的表达明显较低。高风险组中免疫检查点基因如 CD28、CTLA4 和 PDCD1 的表达显著下降。候选 lncRNA 的靶基因得到了证实，如 ENO2 和 PPAR-γ。此外，MIR4435-2HG 在 HNSCC 细胞系和肿瘤样本中表达最显著上调，它可以促进增殖和迁移，抑制凋亡。此外，MIR4435-2HG 沉默通过增加 LC3B 表达激活自噬。
本研究构建了 HNSCC 的 LR-lncRNA 预后模型，并表明其与肿瘤免疫和自噬的关系，为基于 LR-lncRNA 的预后工具和治疗靶点提供了有前景的未来。
