Wallbillich John J, Tran Paul Mh, Bai Shan, Tran Lynn Kh, Sharma Ashok K, Ghamande Sharad A, She Jin-Xiong
Center for Biotechnology and Genomic Medicine, Medical College of Georgia at Augusta University Augusta, GA, USA.
Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Medical College of Georgia at Augusta University Augusta, GA, USA.
Am J Cancer Res. 2020 May 1;10(5):1534-1547. eCollection 2020.
Survival for patients with newly diagnosed cervical cancer has not significantly improved over the past several decades. We sought to identify a clinically relevant set of prognostic genes for squamous cell carcinoma of the cervix (SCCC), the most common cervical cancer subtype. Using RNA-sequencing data and survival data from 203 patients in The Cancer Genome Atlas (TCGA), we conducted a series of analyses using different decile cutoffs for gene expression to identify genes that could indicate large and consistent survival differences across different decile cutoffs of gene expression. Those analyses identified 42 high-risk genes. A patient's survivability could be estimated by simply counting the number of high-risk genes with extremely high expression (above the 90 percentile) or estimating a transcriptomic risk score (TRS) using a machine learning algorithm with 9 of the 42 genes. On multivariate analysis, the significant predictors of mortality included high TRS (HR = 44.8), stage IV (HR = 28.1), intermediate TRS (HR = 4.75), and positive lymph node status (HR = 2.92). Approximately 18% of earlier-stage patients were identified as a poor-prognosis subgroup with high TRS. In patients with SCCC, transcriptomic risk appears to better predict survival than clinical prognostic factors, including stage.
在过去几十年中，新诊断出的宫颈癌患者的生存率并未得到显著提高。我们试图为子宫颈鳞状细胞癌（SCCC，最常见的宫颈癌亚型）确定一组具有临床相关性的预后基因。利用来自癌症基因组图谱（TCGA）中203名患者的RNA测序数据和生存数据，我们使用不同的基因表达十分位数临界值进行了一系列分析，以确定那些在不同基因表达十分位数临界值下能够显示出巨大且一致的生存差异的基因。这些分析确定了42个高风险基因。通过简单计算具有极高表达（高于第90百分位数）的高风险基因数量，或者使用包含42个基因中的9个基因的机器学习算法估计转录组风险评分（TRS），可以估算患者的生存能力。在多变量分析中，死亡率的显著预测因素包括高TRS（HR = 44.8）、IV期（HR = 28.1）、中等TRS（HR = 4.75）和阳性淋巴结状态（HR = 2.92）。约18%的早期患者被确定为具有高TRS的预后不良亚组。在SCCC患者中，转录组风险似乎比包括分期在内的临床预后因素更能预测生存情况。
