Wong Nathan, Khwaja Shariq S, Baker Callie M, Gay Hiram A, Thorstad Wade L, Daly Mackenzie D, Lewis James S, Wang Xiaowei
Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri.
Department of Biomedical Engineering, Washington University, St. Louis, Missouri.
Cancer Med. 2016 Jul;5(7):1619-28. doi: 10.1002/cam4.718. Epub 2016 Apr 25.
Identification of novel prognostic biomarkers typically requires a large dataset which provides sufficient statistical power for discovery research. To this end, we took advantage of the high-throughput data from The Cancer Genome Atlas (TCGA) to identify a set of prognostic biomarkers in head and neck squamous cell carcinomas (HNSCC) including oropharyngeal squamous cell carcinoma (OPSCC) and other subtypes. In this study, we analyzed miRNA-seq data obtained from TCGA patients to identify prognostic biomarkers for OPSCC. The identified miRNAs were further tested with an independent cohort. miRNA-seq data from TCGA was also analyzed to identify prognostic miRNAs in oral cavity squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC). Our study identified that miR-193b-3p and miR-455-5p were positively associated with survival, and miR-92a-3p and miR-497-5p were negatively associated with survival in OPSCC. A combined expression signature of these four miRNAs was prognostic of overall survival in OPSCC, and more importantly, this signature was validated in an independent OPSCC cohort. Furthermore, we identified four miRNAs each in OSCC and LSCC that were prognostic of survival, and combined signatures were specific for subtypes of HNSCC. A robust 4-miRNA prognostic signature in OPSCC, as well as prognostic signatures in other subtypes of HNSCC, was developed using sequencing data from TCGA as the primary source. This demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care.
鉴定新的预后生物标志物通常需要一个大型数据集，该数据集能够为发现研究提供足够的统计效力。为此，我们利用来自癌症基因组图谱（TCGA）的高通量数据，来鉴定一组头颈部鳞状细胞癌（HNSCC）中的预后生物标志物，包括口咽鳞状细胞癌（OPSCC）和其他亚型。在本研究中，我们分析了从TCGA患者获得的miRNA测序数据，以鉴定OPSCC的预后生物标志物。所鉴定的miRNA在一个独立队列中进一步进行了检测。我们还分析了来自TCGA的miRNA测序数据，以鉴定口腔鳞状细胞癌（OSCC）和喉鳞状细胞癌（LSCC）中的预后miRNA。我们的研究发现，miR-193b-3p和miR-455-5p与OPSCC患者的生存呈正相关，而miR-92a-3p和miR-497-5p与生存呈负相关。这四种miRNA的联合表达特征对OPSCC的总生存具有预后价值，更重要的是，该特征在一个独立的OPSCC队列中得到了验证。此外，我们在OSCC和LSCC中分别鉴定出四种对生存具有预后价值的miRNA，并且联合特征对HNSCC的不同亚型具有特异性。以TCGA的测序数据作为主要来源，开发了一种强大的OPSCC中4-miRNA预后特征，以及HNSCC其他亚型中的预后特征。这证明了利用TCGA作为潜在资源来开发预后工具以改善个体化患者护理的作用。
