Department of General Surgery, Ningde Municipal Hospital of Ningde Normal University, Ningde, China.
Carol & Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine & Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
Front Endocrinol (Lausanne). 2023 Jan 16;13:1076521. doi: 10.3389/fendo.2022.1076521. eCollection 2022.
The significance of nucleotide metabolism and neuroendocrine in cellular immune response and cancer is becoming more well-established. However, the mechanisms underlying nucleotide metabolism and neuroendocrine involvement in stomach adenocarcinoma (STAD) remain unclear.
First, a pan-cancer overview of nucleotide metabolism and neuroendocrine-related genes (NMNGs) was explored through the integration of expression profiles, prognostic values, mutation information, methylation levels, and pathway-regulation relationships. We next extensively assessed variations in prognosis and tumor microenvironment (TME) features across the various modification patterns, based on an extensive analysis of the NMNG modification patterns of 808 STAD samples based on 46 NMNGs. Utilizing principal component analysis methodologies, the NMNGscore was developed to measure NMNG alteration patterns of individual tumors.
Pan-cancer analysis shows that NMNGs mostly act as risk genes in multiple cancer types, especially in STAD. Based on the NMNGs we detected two different NMNG modification patterns in STAD. Both patterns showed distinct immune cell infiltration features and biological behavior, with NMNGcluster A exhibiting a worse prognosis and a larger amount of immune infiltration. Differentially expressed genes with prognostic relevance were used to classify the STAD samples into three genomic subgroups. Analysis of survival rates revealed that cluster B genes were associated with longer life expectancy than clusters A and C. Individual STAD patients' NMNG alteration patterns were analyzed by analyzing their NMNGscore signatures. NMNGscore and immune cells showed a statistically significant adverse correlation with each other. Increased longevity, a higher incidence of mutations, and a better response to immunotherapy were associated with patients' NMNG scores.
Our findings provide a personalized prediction tool for prognosis and immunotherapy sensitivity in patients, as well as a promising knowledge of nucleotide metabolism and neuroendocrine in STAD.
核苷酸代谢和神经内分泌在细胞免疫反应和癌症中的意义变得越来越明确。然而，核苷酸代谢和神经内分泌参与胃腺癌（STAD）的机制仍不清楚。
首先，通过整合表达谱、预后价值、突变信息、甲基化水平和通路调节关系，对核苷酸代谢和神经内分泌相关基因（NMNGs）进行了泛癌概述。接下来，我们根据对 808 个 STAD 样本基于 46 个 NMNG 的 NMNG 修饰模式的广泛分析，广泛评估了不同修饰模式下的预后和肿瘤微环境（TME）特征的变化。利用主成分分析方法，开发了 NMNGscore 来衡量个体肿瘤的 NMNG 改变模式。
泛癌分析表明，NMNGs 主要作为多种癌症类型的风险基因，特别是在 STAD 中。基于我们检测到的 NMNGs，我们在 STAD 中发现了两种不同的 NMNG 修饰模式。两种模式均表现出不同的免疫细胞浸润特征和生物学行为，NMNGcluster A 表现出更差的预后和更多的免疫浸润。具有预后相关性的差异表达基因用于将 STAD 样本分为三个基因组亚群。生存分析显示，cluster B 基因与更长的预期寿命相关，而 cluster A 和 C 则相反。通过分析其 NMNGscore 特征来分析个体 STAD 患者的 NMNG 改变模式。NMNGscore 和免疫细胞之间存在统计学上显著的负相关。NMNG 评分较高的患者生存期较长、突变发生率较高、对免疫治疗的反应较好。
我们的研究结果为患者的预后和免疫治疗敏感性提供了个性化的预测工具，并为 STAD 中的核苷酸代谢和神经内分泌提供了有前途的知识。
