最新细胞功能及机制文献分享最近的研究表明，长链非编码RNA（lncRNAs）可能参与了肿瘤细胞调控，然而，在结肠腺癌（COAD）中，lncRNA表达与细胞焦亡之间的联系仍不清楚。2021年12月13日，中南大学湘雅医院分子医学中心分子放射肿瘤湖南省重点实验室Cong Shen团队在Frontiers in Cell and Developmental Biology上发表了题为“A Prognostic Pyroptosis-Related lncRNAs Risk Model Correlates With the Immune Microenvironment in Colon Adenocarcinoma”的研究论文。在本研究中，团队旨在基于焦亡相关lncRNA探索和建立COAD的预后特征，确定了来自TCGA-COAD数据集中的15种与预后相关的lncRNA，为预测COAD患者的预后和确定个性化治疗策略提供了新的参考。结直肠癌（CRC）是最常见的恶性肿瘤之一，也是全球癌症相关死亡的第三大原因。根据病理学分类，COAD是CRC最常见的亚型。近年来，青少年COAD的发病率呈上升趋势，目前，无远处转移的COAD患者5年总生存率（OS）预后良好，但转移患者的5年总生存率不足15%。细胞焦亡（Pyroptosis）是一种新发现的依赖于炎症小体的程序性细胞死亡（PCD）机制，其特征是质膜孔形成，导致细胞肿胀和破裂，以及促炎内容物逸出。细胞焦亡是一把双刃剑，在抵抗细菌和病毒感染方面起着关键作用，并且与肿瘤发展直接相关，可通过免疫与肿瘤微环境之间的交联参与抗肿瘤反应。大量研究表明，lncRNA在肿瘤发生发展中不可或缺，甚至可改变肿瘤特性，导致肿瘤微环境差异。在这项研究中，团队系统地探讨了细胞焦亡相关lncRNA之间的关系，并探讨了COAD临床病理信息与肿瘤免疫现象。团队首先筛选了15个差异表达的细胞焦亡相关lncRNA（ZNF667-AS1、OIP5-AS1、AL118506.1、AF117829.1、POC1B-AS1、CCDC18-AS1、THUMPD3-AS1、FLNB-AS1、SNHG11、DHAL70718218-AS1、LINC00641、FGD5-AS1和AC245452.1）以构建预后风险模型；之后，根据风险评分的中位数截断值，将COAD患者分为高危组和低危组，评估两组的免疫状态；据此，构建了免疫风险模型。最后，结合可预测的临床病理特征、风险评分和免疫风险评分构建了一个有效的列线图来预测COAD患者的生存率。结果表明，基于焦亡相关lncRNA的预后特征是COAD患者的一种强大的预测方法。同时，风险评分与免疫微环境之间的关系可显示出预后不良的潜在影响因素。在整合传统的临床病理信息、风险评分和免疫风险评分后，构建了独特的预后评估系统。列线图在基因水平和临床预后之间建立了联系。多维度综合考虑影响COAD患者预后的因素，为临床治疗奠定了坚实的基础。也就是说，细胞焦亡相关lncRNAs表现出其预测COAD患者临床结果的能力，并参与了免疫微环境细胞反应。图 本研究的流程图。期刊及DOI号Front Cell Dev Biol. 2021 Dec 13. doi: 10.3389/fcell.2021.811734.题目A Prognostic Pyroptosis-Related lncRNAs Risk Model Correlates With the Immune Microenvironment in Colon Adenocarcinoma摘要Recent studies have indicated that long non-coding RNAs (lncRNAs) may participate in the regulation of tumor cell proptosis. However, the connection between lncRNA expression and pyroptosis remains unclear in colon adenocarcinoma (COAD). This study aims to explore and establish a prognostic signature of COAD based on the pyroptosis-related lncRNAs. We identify 15 prognostic pyroptosis-related lncRNAs (ZNF667-AS1, OIP5-AS1, AL118506.1, AF117829.1, POC1B-AS1, CCDC18-AS1, THUMPD3-AS1, FLNB-AS1, SNHG11, HCG18, AL021707.2, UGDH-AS1, LINC00641, FGD5-AS1 and AC245452.1) from the TCGA-COAD dataset and use them to construct the risk model. After then, this pyroptosis-related lncRNA signature is validated in patients from the GSE17536 dataset. The COAD patients are divided into low-risk and high-risk groups by setting the median risk score as the cut-off point and represented differences in the immune microenvironment. Hence, we construct the immune risk model based on the infiltration levels of ssGSEA immune cells. Interestingly, the risk model and immune risk model are both independent prognostic risk factors. Therefore, a nomogram combined risk score, immune risk score with clinical information which is meaningful in univariate and multivariate Cox regression analysis is established to predict the overall survival (OS) of COAD patients. In general, the signature consisted of 15 pyroptosis-related lncRNAs and was proved to be associated with the immune landscape of COAD patients.
