基于口腔鳞状细胞癌中顺铂耐药相关基因的预后模型

IF 1.4 4区 医学 Q3 DENTISTRY, ORAL SURGERY & MEDICINE Oral health & preventive dentistry Pub Date : 2024-01-15 DOI:10.3290/j.ohpd.b4836127
Rong Lu, Qian Yang, Siyu Liu, Lu Sun
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引用次数: 0

摘要

目的:筛选口腔鳞状细胞癌(OSCC)中与顺铂耐药相关的预后特征,并评估其与免疫微环境的相关性:从TCGA和GEO数据库下载与OSCC和顺铂耐药相关的基因表达数据。根据肿瘤组与对照组、顺铂耐药样本与亲代样本之间差异表达基因(DEGs)的交集,筛选出顺铂耐药基因。然后,通过单变量 Cox 回归和 LASSO 回归分析,进一步筛选出与预后相关的顺铂耐药基因,构建生存预后模型。利用 MSigDB v7.1 数据库在两个风险组之间进行了 GSEA(基因组富集分析)。最后,利用 CIBERSORT 对样本的免疫格局进行了研究。使用 pRRophetic 0.5 预测了 57 种药物的 IC50 值:结果:共获得 230 个候选基因。结果:共获得 230 个候选基因,然后利用 LASSO 回归分析法筛选出 7 个耐药基因用于构建预后风险评分(RS)特征,包括 STC2、TBC1D2、ADM、NDRG1、OLR1、PDGFA 和 ANO1。RS是一个独立的预后因素。此外,还建立了一个提名图模型来预测样本的1年、2年和3年生存率。GSEA发现了两个风险组之间的几种不同通路,如EMT、缺氧和氧化磷酸化。有15种免疫细胞在两组间的浸润水平存在统计学差异,如巨噬细胞M2和静息NK细胞。共有 57 种药物的 IC50 值在两个风险组之间存在明显统计学差异:这些模型基因和免疫细胞可能在预测 OSCC 的预后和化疗耐药性方面发挥作用。
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A Prognostic Model Based on Cisplatin-Resistance Related Genes in Oral Squamous Cell Carcinoma.

Purpose: To screen for the cisplatin resistance-related prognostic signature in oral squamous cell carcinoma (OSCC) and assess its correlation with the immune microenvironment.

Materials and methods: The gene expression data associated with OSCC and cisplatin-resistance were downloaded from TCGA and GEO databases. Cisplatin-resistant genes were selected through taking the intersection of differentially expressed genes (DEGs) between tumor and control groups as well as between cisplatin-resistant samples and parental samples. Then, prognosis-related cisplatin-resistant genes were further selected by univariate Cox regression and LASSO regression analyses to construct a survival prognosis model. A GSEA (gene set enrichment analysis) between two risk groups was conducted with the MSigDB v7.1 database. Finally, the immune landscape of the sample was studied using CIBERSORT. The IC50 values of 57 drugs were predicted using pRRophetic 0.5.

Results: A total 230 candidate genes were obtained. Then 7 drug-resistant genes were selected for prognostic risk-score (RS) signature construction using LASSO regression analysis, including STC2, TBC1D2, ADM, NDRG1, OLR1, PDGFA and ANO1. RS was an independent prognostic factor. Additionally, a nomogram model was established to predict the 1-, 2-, and 3-year survival rates of samples. The GSEA identified several differential pathways between two risk groups, such as EMT, hypoxia, and oxidative phosphorylation. Fifteen immune cells were statistically significantly different in infiltration level between the two groups, such as macrophages M2, and resting NK cells. A total of 57 drugs had statistically significantly different IC50 values between two risk groups.

Conclusion: These model genes and immune cells may play a role in predicting the prognosis and chemoresistance in OSCC.

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来源期刊
Oral health & preventive dentistry
Oral health & preventive dentistry DENTISTRY, ORAL SURGERY & MEDICINE-
CiteScore
3.00
自引率
0.00%
发文量
51
审稿时长
>12 weeks
期刊介绍: Clinicians, general practitioners, teachers, researchers, and public health administrators will find this journal an indispensable source of essential, timely information about scientific progress in the fields of oral health and the prevention of caries, periodontal diseases, oral mucosal diseases, and dental trauma. Central topics, including oral hygiene, oral epidemiology, oral health promotion, and public health issues, are covered in peer-reviewed articles such as clinical and basic science research reports; reviews; invited focus articles, commentaries, and guest editorials; and symposium, workshop, and conference proceedings.
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