Department of Urology, First Affiliated Hospital of Nanchang University, Nanchang, China.
Front Immunol. 2023 Aug 11;14:1225023. doi: 10.3389/fimmu.2023.1225023. eCollection 2023.
Both lactylation and m6A modification have important implications for the development of clear cell renal cell carcinoma (ccRCC), and we aimed to use crosstalk genes of both to reveal the prognostic and immunological features of ccRCC.
Our first step was to look for lactylation-related genes that differed between normal and tumor tissues, and then by correlation analysis, we found the genes associated with M6A. Following that, ccRCC subtypes will be identified and risk models will be constructed to compare the prognosis and tumor microenvironment among different subgroups. A nomogram was constructed to predict the prognosis of ccRCC, and , experiments were conducted to validate the expression and function of key genes.
We screened 100 crosstalk genes and identified 2 ccRCC subtypes. A total of 11 prognostic genes were screened for building a risk model. we observed higher immune scores, elevated tumor mutational burden, and microsatellite instability scores in the high-risk group. Therefore, individuals classified as high-risk would derive greater benefits from immunotherapy. The nomogram's ability to predict overall survival with a 1-year AUC of 0.863 demonstrates its significant practical utility. In addition, HIBCH was identified as a potential therapeutic target and its expression and function were verified by experiments.
In addition to developing a precise prognostic nomogram for patients with ccRCC, our study also discovered the potential of HIBCH as a biomarker for the disease.
乳糖化和 m6A 修饰对透明细胞肾细胞癌（ccRCC）的发展都有重要意义，我们旨在利用这两种修饰的串扰基因来揭示 ccRCC 的预后和免疫特征。
我们首先寻找正常组织和肿瘤组织之间差异表达的乳糖化相关基因，然后通过相关性分析，找到与 M6A 相关的基因。之后，将鉴定 ccRCC 亚型，并构建风险模型以比较不同亚组之间的预后和肿瘤微环境。构建列线图预测 ccRCC 的预后，并进行实验验证关键基因的表达和功能。
我们筛选了 100 个串扰基因，鉴定了 2 个 ccRCC 亚型。共筛选了 11 个预后基因构建风险模型。我们观察到高危组的免疫评分更高，肿瘤突变负担和微卫星不稳定性评分升高。因此，高风险组的患者从免疫治疗中获益更大。列线图预测总生存期的能力，1 年 AUC 为 0.863，表明其具有显著的实际应用价值。此外，通过实验验证了 HIBCH 作为潜在治疗靶点的表达和功能。
本研究不仅为 ccRCC 患者开发了精确的预后列线图，还发现了 HIBCH 作为疾病生物标志物的潜力。
