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基底膜相关基因表达作为口腔癌生存预测的指标。

Basement membrane-associated gene expression as a predictor of survival in oral cancer.

机构信息

Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, Laboratory of Clinical Applied Anatomy, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, China.

Department of Oramaxillofacial - Head and Neck Surgery, School of Medicine, Tianjin Stomatological Hospital, Nankai University, Tianjin, 300041, China.

出版信息

BMC Cancer. 2024 Jun 14;24(1):731. doi: 10.1186/s12885-024-12485-2.

Abstract

BACKGROUND

This study sought to investigate the prognostic value of basement membrane (BM)-associated gene expressions in oral cancer.

METHODS

We harvested and integrated data on BM-associated genes (BMGs), the oral cancer transcriptome, and clinical information from public repositories. After identifying differentially expressed BMGs, we used Cox and Lasso regression analyses to create a BMG-based risk score for overall survival at various intervals. We then validated this score using the GSE42743 cohort as a validation set. The prognostic potential of the risk scores and their relations to clinical features were assessed. Further, we conducted functional pathway enrichment, immune cell infiltration, and immune checkpoint analyses to elucidate the immunological implications and therapeutic potential of the BMG-based risk score and constituent genes. To confirm the expression levels of the BMG LAMA3 in clinical samples of oral cancer tissue, we performed quantitative real-time PCR (qRT-PCR) and immunohistochemical staining.

RESULTS

The BMGs LAMA3, MMP14, and GPC2 demonstrated notable prognostic significance, facilitating the construction of a BMG-based risk score. A higher risk score derived from BMGs correlated with a poorer survival prognosis for oral cancer patients. Moreover, the risk-associated BMGs exhibited a significant relationship with immune function variability (P < 0.05), discrepancies in infiltrating immune cell fractions, and immune checkpoint expressions (P < 0.05). The upregulated expression levels of LAMA3 in oral cancer tissues were substantiated through qRT-PCR and immunohistochemical staining.

CONCLUSION

The BMG-based risk score emerged as a reliable prognostic tool for oral cancer, meriting further research for validation and potential clinical application.

摘要

背景

本研究旨在探讨基底膜(BM)相关基因表达在口腔癌中的预后价值。

方法

我们从公共数据库中收集并整合了与 BM 相关的基因(BMGs)、口腔癌转录组和临床信息的数据。在确定差异表达的 BMG 后,我们使用 Cox 和 Lasso 回归分析创建了基于 BMG 的总生存率风险评分,用于不同时间间隔。然后,我们使用 GSE42743 队列作为验证集验证了该评分。评估了风险评分的预后潜力及其与临床特征的关系。此外,我们进行了功能途径富集、免疫细胞浸润和免疫检查点分析,以阐明基于 BMG 的风险评分及其组成基因的免疫意义和治疗潜力。为了确认 BMG LAMA3 在口腔癌组织临床样本中的表达水平,我们进行了定量实时 PCR(qRT-PCR)和免疫组织化学染色。

结果

BMG LAMA3、MMP14 和 GPC2 表现出显著的预后意义,有助于构建基于 BMG 的风险评分。从 BMG 中得出的较高风险评分与口腔癌患者的生存率较差相关。此外,风险相关的 BMG 与免疫功能变异性(P < 0.05)、浸润免疫细胞分数和免疫检查点表达的差异显著相关(P < 0.05)。通过 qRT-PCR 和免疫组织化学染色证实了 LAMA3 在口腔癌组织中的上调表达水平。

结论

基于 BMG 的风险评分是一种可靠的口腔癌预后工具,值得进一步研究验证和潜在的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e58e/11177517/6741c45682b4/12885_2024_12485_Fig1_HTML.jpg

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