Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, China.
Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China.
Gene. 2025 Jan 10;932:148898. doi: 10.1016/j.gene.2024.148898. Epub 2024 Aug 30.
Lactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear.
Gene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified.
The immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor's development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells.
This study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.
乳酸（LA）可以通过与肿瘤微环境（TME）的串扰促进肿瘤的恶性进展。然而，与 LA 代谢相关的长非编码 RNA（lncRNA）在肾母细胞瘤（WT）中的功能尚不清楚。
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中收集 WT 患者的基因表达数据和临床数据。通过 ESTIMATE 算法和 Pearson 相关性分析，筛选与肿瘤免疫和 LA 代谢相关的 lncRNA。随后，进行 Cox 回归分析和 Lasso Cox 回归分析构建模型。进一步确定候选基因，并构建竞争性内源 RNA（ceRNA）网络以探索特征基因的具体机制。最后，基于 UNC5B-AS1 的强临床相关性，对其表达和功能进行了实验验证。
免疫评分和基质评分与 WT 的预后密切相关。最终，成功鉴定出由 6 个 lncRNA 组成的预后模型（TME-LA-LM）。该模型表现出良好的预测能力和准确性，风险组之间观察到免疫浸润和药物敏感性的显著变化。此外，该研究还揭示了 2 个候选基因和 5 个 microRNAs（miRNAs）参与肿瘤的发生。值得注意的是，UNC5B-AS1 表达较高，并且发现其促进肿瘤细胞的增殖和迁移。
本研究首次利用与 TME 和 LA 代谢相关的 lncRNA 阐明了 WT 的预后特征。本研究的资金为未来的免疫治疗、个性化化疗和机制研究提供了有价值的见解。
