研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

焦亡相关的长非编码 RNA 特征可预测肺鳞状细胞癌患者的生存和免疫治疗效果。

Pyroptosis-related long-noncoding RNA signature predicting survival and immunotherapy efficacy in patients with lung squamous cell carcinoma.

发表日期:2024 Jul 03
作者: Xiang Zhan, Jixian Li, Yi Ding, Fengge Zhou, Renya Zeng, Lingli Lei, Ying Zhang, Alei Feng, Yan Qu, Zhe Yang
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

细胞焦亡相关的长链非编码 RNA (PRlncRNA) 在癌症进展中发挥着重要作用。然而,它们在肺鳞状细胞癌(LUSC)中的作用尚不清楚。基于癌症基因组图谱数据库的 RNA 测序数据,使用最小绝对收缩和选择算子 (LASSO) Cox 回归分析构建了风险模型。 LUSC 队列根据中位风险评分分为高风险组和低风险组。对于模型的预后价值,进行了Kaplan-Meier分析、对数秩检验和Cox回归分析。使用风险评分和年龄、性别、临床分期和肿瘤淋巴结转移分类(TNM)分期等临床参数构建列线图来预测患者的预后。随后,采用六种常见算法来评估免疫细胞的入侵。进行基因集富集分析(GSEA)来识别高风险和低风险患者之间的差异。此外,pRRophetic 软件包用于预测流行化疗药物的半最大抑制剂量,同时计算肿瘤免疫功能障碍和排除评分以预测对免疫治疗的反应。使用 RT-qPCR 检查 LUSC 和正常肺上皮细胞系中 7 种 PRlncRNA 的表达水平。还进行了增殖、迁移和侵袭测定,以研究 MIR193BHG 在 LUSC 细胞中的作用。在总队列或亚组分析中,低风险组患者的生存期延长。 Cox回归分析显示,风险模型可以作为LUSC患者的独立预后因素。 GSEA分析结果显示,高危组表现出细胞因子通路、Janus酪氨酸激酶/信号转导器和转录信号通路激活剂、Toll样受体通路的富集。相反,低风险组表现出多种基因修复途径的富集。此外,风险评分与免疫细胞浸润呈正相关。此外,高危类别的患者对传统化疗药物和免疫疗法的反应性降低。通过体外测试证实,与正常肺上皮细胞系相比,风险模型中的大多数长非编码RNA在LUSC细胞系中过度表达。进一步的研究表明,下调MIR193BHG的表达可能会抑制LUSC细胞的生长、运动和浸润能力,而增加MIR193BHG的表达可能会增强这些恶性倾向。本研究发现 PRlncRNA 与 LUSC 患者的预后相关。该风险模型通过各种临床参数和治疗方式进行评估,显示出作为未来临床应用参考的潜力。© 2024。作者。
Pyroptosis-related long-noncoding RNAs (PRlncRNAs) play an important role in cancer progression. However, their role in lung squamous cell carcinoma (LUSC) is unclear. A risk model was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis based on RNA sequencing data from The Cancer Genome Atlas database. The LUSC cohort was divided into high- and low-risk groups based on the median risk score. For the prognostic value of the model, the Kaplan-Meier analysis, log-rank test, and Cox regression analysis were performed. A nomogram was constructed to predict the prognosis of patients, using a risk score and clinical parameters such as age, sex, clinical stage, and tumor node metastasis classification (TNM) stage. Afterwards, six common algorithms were employed to assess the invasion of immune cells. The Gene Set Enrichment Analysis (GSEA) was conducted to identify differences between patients at high and low risk. Furthermore, the pRRophetic package was employed to forecast the half-maximal inhibitory doses of prevalent chemotherapeutic drugs, while the tumor immune dysfunction and exclusion score was computed to anticipate the response to immunotherapy. The expression levels of the seven PRlncRNAs were examined in both LUSC and normal lung epithelial cell lines using RT-qPCR. Proliferation, migration, and invasion assays were also carried out to investigate the role of MIR193BHG in LUSC cells. Patients in the low-risk group showed prolonged survival in the total cohort or subgroup analysis. The Cox regression analysis showed that the risk model could act as an independent prognostic factor for patients with LUSC. The results of GSEA analysis revealed that the high-risk group showed enrichment of cytokine pathways, Janus tyrosine kinase/signal transducer and activator of the transcription signalling pathway, and Toll-like receptor pathway. Conversely, the low-risk group showed enrichment of several gene repair pathways. Furthermore, the risk score was positively correlated with immune cell infiltration. Moreover, patients in the high-risk category showed reduced responsiveness to conventional chemotherapeutic medications and immunotherapy. The majority of the long noncoding RNAs in the risk model were confirmed to be overexpressed in LUSC cell lines compared to normal lung epithelial cell lines by in vitro tests. Further studies have shown that downregulating the expression of MIR193BHG may inhibit the growth, movement, and infiltration capabilities of LUSC cells, whereas increasing the expression of MIR193BHG could enhance these malignant tendencies. This study found that PRlncRNAs were linked to the prognosis of LUSC patients. The risk model, evaluated across various clinical parameters and treatment modalities, shows potential as a future reference for clinical applications.© 2024. The Author(s).