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基于免疫相关 lncRNAs 的胃腺癌预后评估模型的构建。

Construction of a Prognostic Evaluation Model for Stomach Adenocarcinoma on the Basis of Immune-Related lncRNAs.

机构信息

Department of Gastrointestinal Surgery, Lishui City People's Hospital, 15# Dazhong Street Zhejiang Province, 323000, Lishui, China.

出版信息

Appl Biochem Biotechnol. 2022 Dec;194(12):6255-6269. doi: 10.1007/s12010-022-04098-x. Epub 2022 Jul 29.

Abstract

Progression, prognosis, and therapeutic strategy of stomach adenocarcinoma (STAD) have a close connection with tumor microenvironment (TME). Thus, it is pivotal to delve into the TME and immune-related genes, which may bring possibilities for improving patient's prognosis. TCGA-STAD dataset was analyzed to acquire differentially expressed lncRNAs in tumor samples, which were overlapped with the immune-related lncRNA datasets in the ImmLnc database. Twenty-six lncRNAs related to STAD immunity and patient's prognosis were acquired by univariate Cox analysis. Following lncRNA expression patterns, STAD samples could be classified into two clusters with completely different immune patterns. We performed multivariate Cox regression analysis on lncRNAs to identify 7-feature lncRNAs and constructed a corresponding prognostic model. The model validity was verified by survival analysis and ROC curve in validation and training sets. To explore connection between model and TME and tumor drug resistance, this study analyzed differences in immune cell infiltration between samples from high- and low-risk groups and then revealed immune cells follicular helper with significant differences in tumor tissue infiltration. Analysis of resistance to chemotherapeutic drugs revealed that samples in the high-risk group had resistance to cisplatin, doxorubicin, bleomycin, and gemcitabine. Through univariate and multivariate Cox analyses, we manifested that risk score could be an independent prognostic factor. Combining risk score and clinical factors, a nomogram was constructed to accurately predict patient's prognosis. This model can effectively predict prognosis, TME, and drug resistance of STAD patients, which may provide a reference for tumor development evaluation and precise treatment for clinical STAD.

摘要

胃腺癌(STAD)的进展、预后和治疗策略与肿瘤微环境(TME)密切相关。因此,深入研究 TME 和免疫相关基因可能为改善患者预后带来可能。分析 TCGA-STAD 数据集以获取肿瘤样本中差异表达的 lncRNA,这些 lncRNA 与 ImmLnc 数据库中的免疫相关 lncRNA 数据集重叠。通过单因素 Cox 分析获得与 STAD 免疫和患者预后相关的 26 个 lncRNA。根据 lncRNA 的表达模式,STAD 样本可分为两个具有完全不同免疫模式的簇。我们对 lncRNA 进行多因素 Cox 回归分析,以识别 7 个特征性 lncRNA,并构建相应的预后模型。该模型在验证和训练集中通过生存分析和 ROC 曲线进行了验证。为了探索模型与 TME 和肿瘤耐药性之间的关系,本研究分析了高风险和低风险组样本之间免疫细胞浸润的差异,然后揭示了肿瘤组织浸润中具有显著差异的滤泡辅助性免疫细胞。对化疗药物耐药性的分析表明,高风险组样本对顺铂、阿霉素、博来霉素和吉西他滨具有耐药性。通过单因素和多因素 Cox 分析,我们表明风险评分可以是一个独立的预后因素。结合风险评分和临床因素,构建了一个列线图来准确预测患者的预后。该模型可以有效地预测 STAD 患者的预后、TME 和药物耐药性,为肿瘤发展评估和临床 STAD 的精确治疗提供参考。

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