PO.PR01.02 · 预防研究
唾液转录组特征揭示口腔潜在恶性疾病中的早期分子重编程：印度患者中一种无创精准肿瘤学方法
Salivary transcriptomic signatures reveal early molecular reprogramming in oral potentially malignant disorders: A non-invasive precision oncology approach in indian patients
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：口腔潜在恶性疾病（OPMD），如口腔扁平苔藓、白斑和红斑，具有不同的恶性转化风险，常难以在临床上早期识别。唾液提供了一种无创、分子丰富的生物液体，可用于检测反映致癌区域改变的转录组变化。
方法：在这项横断面研究中，对96名参与者（48例OPMD病例，48例年龄和性别匹配的对照）的非刺激唾液样本，在印度CSIR-IGIB使用Illumina NovaSeq 6000平台进行RNA测序。进行了质量控制（FastQC）、比对（STAR）和差异表达分析（DESeq2和edgeR）。功能富集采用GSEA和Reactome通路。诊断建模使用LASSO正则化逻辑回归和ROC分析。
结果：转录组分析揭示了1,126个显著失调的基因（|log₂FC| > 1.5，FDR < 0.05），包括MMP9、IL6、CXCL8、TP63的上调以及KRT13、LOR、SPRR2A的下调。通路富集提示涉及PI3K/AKT、p53和上皮-间质转化信号。15基因唾液特征在区分OPMD与对照方面产生了AUC = 0.94（95% CI 0.89-0.97），敏感性 = 91%，特异性 = 88%。亚组分析确定TP63-CXCL8共激活是转化潜能的预测因子（p = 3.2 × 10⁻⁵，校正p < 0.01）。
结论：高通量唾液转录组学在识别口腔癌变之前的分子失调方面展现出强大的判别能力。这一15基因特征可作为无创生物标志物组合，用于OPMD的早期风险分层，在资源有限环境下的人群水平筛查项目中具有潜在应用价值。
查看英文原文 English abstract
Background: Oral potentially malignant disorders (OPMDs) such as oral lichen planus, leukoplakia, and erythroplakia exhibit variable malignant transformation risk, often eluding early clinical recognition. Saliva offers a non-invasive, molecularly rich biofluid for detecting transcriptomic alterations reflective of oncogenic field changes.
Methods: In this cross-sectional study, unstimulated saliva samples from 96 participants (48 OPMD cases, 48 age- and sex-matched controls) were subjected to RNA sequencing using the Illumina NovaSeq 6000 platform at CSIR-IGIB, India. Quality control (FastQC), alignment (STAR), and differential expression analyses (DESeq2 and edgeR) were performed. Functional enrichment employed GSEA and Reactome pathways. Diagnostic modeling used LASSO-regularized logistic regression and ROC analysis.
Results: Transcriptomic profiling revealed 1,126 significantly dysregulated genes (|log₂FC| > 1.5, FDR < 0.05), including upregulation of MMP9, IL6, CXCL8, TP63, and downregulation of KRT13, LOR, SPRR2A. Pathway enrichment implicated PI3K/AKT, p53, and epithelial-mesenchymal transition signaling. The 15-gene salivary signature yielded an AUC = 0.94 (95% CI 0.89-0.97) for discriminating OPMD from controls, with sensitivity = 91% and specificity = 88%. Sub-analysis identified TP63-CXCL8 co-activation as a predictor of transformation potential (p = 3.2 × 10⁻⁵, adjusted p < 0.01).
Conclusion: High-throughput salivary transcriptomics demonstrates robust discriminatory power for identifying molecular dysregulation preceding oral carcinogenesis. This 15-gene signature may serve as a non-invasive biomarker panel for early risk stratification of OPMD, with potential application in population-level screening programs in resource-limited settings.
利益披露 Disclosure
S. Sampoornam Pape, None.