Viet Chi T, Asam Kesava R, Yu Gary, Dyer Emma C, Kochanny Sara, Thomas Carissa M, Callahan Nicholas F, Morlandt Anthony B, Cheng Allen C, Patel Ashish A, Roden Dylan F, Young Simon, Melville James, Shum Jonathan, Walker Paul C, Nguyen Khanh K, Kidd Stephanie N, Lee Steve C, Folk Gretchen S, Viet Dan T, Grandhi Anupama, Deisch Jeremy, Ye Yi, Momen-Heravi Fatemeh, Pearson Alexander T, Aouizerat Bradley E
Department of Oral and Maxillofacial Surgery, Loma Linda University School of Dentistry, Loma Linda, CA, USA.
Department of Oral and Maxillofacial Surgery, New York University College of Dentistry, New York, NY, USA.
NPJ Precis Oncol. 2024 Jun 8;8(1):130. doi: 10.1038/s41698-024-00605-x.
Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.
口腔鳞状细胞癌（OSCC）生物标志物研究很少采用多组学生物标志物策略和相关临床病理特征来预测死亡率。在本研究中，我们首次确定了一种综合表观遗传学、基因表达和组织学特征，可区分不同烟草使用史的患者（重度烟草使用史≥10包年与无烟草使用史）。利用癌症基因组图谱（TCGA）队列（n = 257）和一个内部队列（n = 40），我们鉴定出3个表观遗传标记（GPR15、GNG12、GDNF）和13个表达标记（IGHA2、SCG5、RPL3L、NTRK1、CD96、BMP6、TFPI2、EFEMP2、RYR3、DMTN、GPD2、BAALC和FMO3），这些标记在从不吸烟的OSCC患者与有≥10包年吸烟史的患者中表达失调。仅基于吸烟状态和临床病理协变量进行死亡率风险预测是不准确的（c统计量 = 0.57），而综合表观遗传/表达和组织学特征在预测OSCC患者5年死亡率时的c统计量为0.9409。
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