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一种与口腔鳞状细胞癌预后及免疫浸润格局相关的新型溶酶体相关预后标志物。

A novel lysosome-related prognostic signature associated with prognosis and immune infiltration landscape in oral squamous cell carcinoma.

作者信息

Liu Jing-Jing, Xu Zhi-Ming, Liu Ying, Guo Xi-Yuan, Zhang Wei-Bing

机构信息

Department of Stomatology, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, 215125, China.

Department of Stomatology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215008, China.

出版信息

Heliyon. 2024 Feb 14;10(4):e26100. doi: 10.1016/j.heliyon.2024.e26100. eCollection 2024 Feb 29.

Abstract

BACKGROUND

Predicting the outcome of oral squamous cell carcinoma (OSCC) is challenging due to its diverse nature and intricate causes. This research explores how lysosome-associated genes (LRGs) might forecast overall survival (OS) and correlate with immune infiltration in OSCC patients.

METHODS

We analyzed OSCC patients' LRGs' mRNA expression data and clinical details from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through univariate Cox regression, we pinpointed LRGs with prognostic potential. A signature comprising 12 LRGs linked to prognosis was developed via the Least Absolute Shrinkage and Selection Operator (LASSO) in a training dataset. Patients were classified as higher or lower risk based on their risk scores, and the prognostic independence of the risk score was assessed using multivariate analysis. The model's robustness and precision were confirmed through bioinformatics in the GEO test set. Differential gene expression analysis between risk groups highlighted functional disparities, while various immune evaluation methods elucidated immune differences.

RESULTS

The prognostic framework utilized 12 LRGs (SLC46A3, MANBA, NEU1, SDCBP, BRI3, TMEM175, CD164, GPC1, SFTPB, TPP1, Biglycan (BGN) and TMEM192), showing that higher risk was associated with poorer OS. This set of genes independently predicted OS in OSCC, linking LRGs to cellular adhesion and extracellular matrix involvement. Initial assessments using ssGSEA and CIBERSORT suggested that the adverse outcomes in the higher-risk cohort may be tied to immune system deregulation.

CONCLUSION

Twelve-LRGs signature has been identified for OSCC prognosis prediction, offering novel directions for lysosome-targeted therapies against OSCC.

摘要

背景

口腔鳞状细胞癌(OSCC)由于其性质多样和病因复杂,预测其预后具有挑战性。本研究探讨溶酶体相关基因(LRGs)如何预测OSCC患者的总生存期(OS)以及与免疫浸润的相关性。

方法

我们分析了来自癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的OSCC患者LRGs的mRNA表达数据和临床细节。通过单变量Cox回归,我们确定了具有预后潜力的LRGs。在一个训练数据集中,通过最小绝对收缩和选择算子(LASSO)开发了一个由12个与预后相关的LRGs组成的特征。根据风险评分将患者分为高风险或低风险,并使用多变量分析评估风险评分的预后独立性。通过GEO测试集中的生物信息学证实了该模型的稳健性和准确性。风险组之间的差异基因表达分析突出了功能差异,而各种免疫评估方法阐明了免疫差异。

结果

预后框架使用了12个LRGs(SLC46A3、MANBA、NEU1、SDCBP、BRI3、TMEM175、CD164、GPC1、SFTPB、TPP1、双糖链蛋白聚糖(BGN)和TMEM192),表明高风险与较差的OS相关。这组基因独立预测OSCC中的OS,将LRGs与细胞粘附和细胞外基质参与联系起来。使用单样本基因集富集分析(ssGSEA)和CIBERSORT的初步评估表明,高风险队列中的不良结果可能与免疫系统失调有关。

结论

已确定用于OSCC预后预测的12-LRGs特征,为针对OSCC的溶酶体靶向治疗提供了新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf89/10900434/904a1fb9cbbf/gr1.jpg

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