关键词: Basement membrane Immune checkpoint Oral cancer Risk model

Mesh : Humans Mouth Neoplasms / genetics mortality pathology Prognosis Basement Membrane / metabolism pathology Biomarkers, Tumor / genetics Gene Expression Regulation, Neoplastic Transcriptome Female Gene Expression Profiling Male Laminin / genetics

来  源:   DOI:10.1186/s12885-024-12485-2   PDF(Pubmed)

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.
CONCLUSIONS: 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:我们收集并整合了BM相关基因(BMGs)的数据,口腔癌转录组,和来自公共存储库的临床信息。在鉴定差异表达的BMG后,我们使用Cox和Lasso回归分析,为不同时间间隔的总生存期建立基于BMG的风险评分.然后,我们使用GSE42743队列作为验证集验证了该分数。评估了风险评分的预后潜力及其与临床特征的关系。Further,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的风险评分和组成基因的免疫学意义和治疗潜力。为了证实BMGLAMA3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:BMGLAMA3、MMP14和GPC2显示出显著的预后意义,促进基于BMG的风险评分的构建。来自BMG的较高风险评分与口腔癌患者的较差生存预后相关。此外,与风险相关的BMG与免疫功能变异性有显著关系(P<0.05),浸润免疫细胞部分的差异,免疫检查点表达(P<0.05)。通过qRT-PCR和免疫组织化学染色证实了口腔癌组织中LAMA3的上调表达水平。
结论:基于BMG的风险评分成为口腔癌的可靠预后工具,值得进一步研究以进行验证和潜在的临床应用。
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