坐骨神经相关lncRNA在编排免疫浸润和预测结肠腺癌治疗效果中的暗示:一项集成生物信息学分析并进行初步实验证实。
The implication of necroptosis-related lncRNAs in orchestrating immune infiltration and predicting therapeutic efficacy in colon adenocarcinoma: an integrated bioinformatic analysis with preliminarily experimental validation.
发表日期:2023
作者:
Shizhe Li, Xiaotong Wang, Yajun Liu, Junbo Xiao, Jun Yi
来源:
Frontiers in Genetics
摘要:
背景:坏死程序化细胞死亡在结肠腺癌(COAD)中起到重要作用。我们旨在通过利用与坏死程序化相关的长链非编码RNA(NRL)开发患有COAD的免疫浸润与干细胞性之间的关系通过风险评分剖析检测方法。方法:我们的研究基于来自癌基因组图谱(TCGA)的基因表达数据和相关临床信息进行。坏死程序化相关基因(NRGs)从基因组和基因组百科全书(KEGG)数据库中获得。使用皮尔逊相关性分析,Cox回归和最小绝对收缩和选择算子(LASSO)回归确定了NRL预后签名(NRLPS)。运用qRT-PCR方法检测了NRLs的表达。运用多种算法识别了免疫细胞浸润与NRLPS风险评分之间的关系。进一步分析了体细胞突变、肿瘤干性指数(TSI)和药物敏感性。结果:为构建NRLPS,我们研究了15个长链非编码RNA。此外,高风险亚组的NRLPS患者的生存率低于低风险亚组的患者。通过GSEA分析,发现NRL在Notch、Hedgehog和Smoothened通路中丰富。免疫浸润分析显示,两个风险组之间的CD8+T细胞、树突状细胞和CD4+T细胞存在显著差异。此外,我们的NRLPS与肿瘤微环境的调节、肿瘤突变负担(TMB)和干细胞性相关。最后,我们的NRLPS证实在预测COAD患者的免疫治疗和化疗的疗效方面具有潜在应用价值。结论:基于NRLs,为COAD患者开发了一个预后模型,使个体化定制免疫治疗和化疗成为可能。(Li, Wang, Liu, Xiao和Yi, 2023版权所有)
Background: Necroptosis contributes significantly to colon adenocarcinoma (COAD). We aim to assess the relationship between immunoinfiltration and stemness in COAD patients through the development of a risk score profile using necroptosis-related long noncoding RNAs (NRLs). Methods: Our study was based on gene expression data and relevant clinical information from The Cancer Genome Atlas (TCGA). Necroptosis-related genes (NRGs) were obtained from the Kyoto Encyclopedia of Genes and Genome (KEGG) database. Pearson correlation analysis, Cox regression, and least absolute shrinkage and selection operator (LASSO) regression were used to determine the NRL prognositic signature (NRLPS). NRLs expression was examined using qRT-PCR method. Several algorithms were used to identify relationships between immune cell infiltration and NRLPS risk scores. Further analysis of somatic mutations, tumor stemness index (TSI), and drug sensitivity were also explored. Results: To construct NRLPS, 15 lncRNAs were investigated. Furthermore, NRLPS patients with high-risk subgroups had lower survival rates than that of patients with low-risk subgroups. Using GSEA analysis, NRL was found to be enriched in Notch, Hedgehog and Smoothened pathways. Immune infiltration analysis showed significant differences in CD8+ T cells, dendritic cell DCs, and CD4+ T cells between the two risk groups. In addition, our NRLPS showed a relevance with the regulation of tumor microenvironment, tumor mutation burden (TMB) and stemness. Finally, NRLPS demonstrated potential applications in predicting the efficacy of immunotherapy and chemotherapy in patients with COAD. Conclusion: Based on NRLs, a prognostic model was developed for COAD patients that allows a personalized tailoring immunotherapy and chemotherapy to be tailored.Copyright © 2023 Li, Wang, Liu, Xiao and Yi.