Yoon Angela J, Wang Shuang, Kutler David I, Carvajal Richard D, Philipone Elizabeth, Wang Tian, Peters Scott M, LaRoche Dominic, Hernandez Brenda Y, McDowell Bradley D, Stewart Claire R, Momen-Heravi Fatemeh, Santella Regina M
Division of Oral and Maxillofacial Pathology, Department of Pathology & Cell Biology, Columbia University College of Dental Medicine, Columbia University Irving Medical Center, New York, New York.
Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York.
Head Neck. 2020 Aug;42(8):1699-1712. doi: 10.1002/hed.26089. Epub 2020 Jan 25.
For early-stage oral squamous cell carcinoma (OSCC), there is no existing risk-stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer-specific mortality.
A total of 568 early-stage OSCC patients who had surgery only and also with available 5-year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT-PCR. The final 5-plex prognostic marker panel was utilized to generate a cancer-specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts.
The risk score from the 5-plex marker panel consisting of miRNAs-127-3p, 4736, 655-3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low-risk group, the high-risk group had 23-fold increased mortality risk (hazard ratio 23, 95% confidence interval 13-42), with a median time-to-recurrence of 6 months and time-to-death of 11 months (vs >60 months for each among low-risk patient; p < .001).
The miRNA-based 5-plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early-stage OSCC.
对于早期口腔鳞状细胞癌(OSCC),除了传统的TNM分期系统外,尚无现有的风险分层方法来识别癌症特异性死亡高风险患者。
共纳入568例仅接受手术且有5年临床结局数据的早期OSCC患者。通过深度测序分析发现特征性微小RNA(miRNA),并通过qRT-PCR进行验证。利用最终的5重预后标志物组合,通过多变量Cox回归分析生成癌症特异性死亡风险评分。在内部和外部验证队列中对预后标志物进行验证。
由miRNAs-127-3p、4736、655-3p、TNM分期和组织学分级组成的5重标志物组合的风险评分将患者分为四个风险类别。与低风险组相比,高风险组的死亡风险增加了23倍(风险比23,95%置信区间13-42),中位复发时间为6个月,死亡时间为11个月(低风险患者的复发时间和死亡时间均>60个月;p<0.001)。
基于miRNA的5重标志物组合驱动的死亡风险评分公式为评估早期OSCC患者的预后提供了临床实用且可靠的方法。