基于癌症干性的肺腺癌和肺鳞癌预后免疫相关基因特征。
Cancer Stemness-Based Prognostic Immune-Related Gene Signatures in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.
机构信息
Department of Radiation Oncology, and Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, China.
Medical Science and Technology Innovation Center, Shandong First Medical University, Jinan, China.
出版信息
Front Endocrinol (Lausanne). 2021 Oct 21;12:755805. doi: 10.3389/fendo.2021.755805. eCollection 2021.
BACKGROUND
Cancer stem cells (CSCs) refer to cells with self-renewal capability in tumors. CSCs play important roles in proliferation, metastasis, recurrence, and tumor heterogeneity. This study aimed to identify immune-related gene-prognostic models based on stemness index (mRNAsi) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively.
METHODS
X-tile software was used to determine the best cutoff value of survival data in LUAD and LUSC based on mRNAsi. Tumor purity and the scores of infiltrating stromal and immune cells in lung cancer tissues were predicted with ESTIMATE R package. Differentially expressed immune-related genes (DEIRGs) between higher- and lower-mRNAsi subtypes were used to construct prognostic models.
RESULTS
mRNAsi was negatively associated with StromalScore, ImmuneScore, and ESTIMATEScore, and was positively associated with tumor purity. LUAD and LUSC samples were divided into higher- and lower-mRNAsi groups with X-title software. The distribution of immune cells was significantly different between higher- and lower-mRNAsi groups in LUAD and LUSC. DEIRGs between those two groups in LUAD and LUSC were enriched in multiple cancer- or immune-related pathways. The network between transcriptional factors (TFs) and DEIRGs revealed potential mechanisms of DEIRGs in LUAD and LUSC. The eight-gene-signature prognostic model (ANGPTL5, CD1B, CD1E, CNTFR, CTSG, EDN3, IL12B, and IL2)-based high- and low-risk groups were significantly related to overall survival (OS), tumor microenvironment (TME) immune cells, and clinical characteristics in LUAD. The five-gene-signature prognostic model (CCL1, KLRC3, KLRC4, CCL23, and KLRC1)-based high- and low-risk groups were significantly related to OS, TME immune cells, and clinical characteristics in LUSC. These two prognostic models were tested as good ones with principal components analysis (PCA) and univariate and multivariate analyses. Tumor T stage, pathological stage, or metastasis status were significantly correlated with DEIRGs contained in prognostic models of LUAD and LUSC.
CONCLUSION
Cancer stemness was not only an important biological process in cancer progression but also might affect TME immune cell infiltration in LUAD and LUSC. The mRNAsi-related immune genes could be potential biomarkers of LUAD and LUSC. Evaluation of integrative characterization of multiple immune-related genes and pathways could help to understand the association between cancer stemness and tumor microenvironment in lung cancer.
背景
癌症干细胞（CSCs）是指在肿瘤中具有自我更新能力的细胞。CSCs 在增殖、转移、复发和肿瘤异质性中发挥重要作用。本研究旨在分别基于肺癌（LUAD）和肺鳞癌（LUSC）中的干细胞指数（mRNAsi），鉴定免疫相关基因预后模型。
方法
使用 X-tile 软件根据 mRNAsi 确定 LUAD 和 LUSC 中生存数据的最佳截止值。用 ESTIMATE R 包预测肺癌组织中肿瘤纯度和浸润性基质及免疫细胞的评分。使用高和低 mRNAsi 亚组之间差异表达的免疫相关基因（DEIRGs）构建预后模型。
结果
mRNAsi 与基质评分、免疫评分和 ESTIMATE 评分呈负相关，与肿瘤纯度呈正相关。用 X-tile 软件将 LUAD 和 LUSC 样本分为高和低 mRNAsi 组。在 LUAD 和 LUSC 中，高和低 mRNAsi 组之间免疫细胞的分布有显著差异。LUAD 和 LUSC 中两组之间的 DEIRGs 富集在多个癌症或免疫相关途径中。转录因子（TFs）与 DEIRGs 之间的网络揭示了 DEIRGs 在 LUAD 和 LUSC 中的潜在机制。基于 8 个基因的预后模型（ANGPTL5、CD1B、CD1E、CNTFR、CTSG、EDN3、IL12B 和 IL2）的高和低风险组与 LUAD 的总生存期（OS）、肿瘤微环境（TME）免疫细胞和临床特征显著相关。基于 5 个基因的预后模型（CCL1、KLRC3、KLRC4、CCL23 和 KLRC1）的高和低风险组与 LUSC 的 OS、TME 免疫细胞和临床特征显著相关。通过主成分分析（PCA）以及单因素和多因素分析，这两个预后模型被证明是良好的模型。LUAD 和 LUSC 中，肿瘤 T 分期、病理分期或转移状态与预后模型中包含的 DEIRGs 显著相关。
结论
癌症干细胞不仅是癌症进展的重要生物学过程，而且可能影响 LUAD 和 LUSC 中的肿瘤微环境免疫细胞浸润。与 mRNAsi 相关的免疫基因可能是 LUAD 和 LUSC 的潜在生物标志物。评估多个免疫相关基因和途径的综合特征有助于理解癌症干细胞与肺癌肿瘤微环境之间的关联。
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