Tong M, Zheng W, Li H, Li X, Ao L, Shen Y, Liang Q, Li J, Hong G, Yan H, Cai H, Li M, Guan Q, Guo Z
Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
Oncogenesis. 2016 Jul 18;5(7):e242. doi: 10.1038/oncsis.2016.51.
Until recently, few prognostic signatures for colorectal cancer (CRC) patients receiving 5-fluorouracil (5-FU)-based chemotherapy could be used in clinical practice. Here, using transcriptional profiles for a panel of cancer cell lines and three cohorts of CRC patients, we developed a prognostic signature based on within-sample relative expression orderings (REOs) of six gene pairs for stage II-III CRC patients receiving 5-FU-based chemotherapy. This REO-based signature had the unique advantage of being insensitive to experimental batch effects and free of the impractical data normalization requirement. After stratifying 184 CRC samples with multi-omics data from The Cancer Genome Atlas into two prognostic groups using the REO-based signature, we further revealed that patients with high recurrence risk were characterized by frequent gene copy number aberrations reducing 5-FU efficacy and DNA methylation aberrations inducing distinct transcriptional alternations to confer 5-FU resistance. In contrast, patients with low recurrence risk exhibited deficient mismatch repair and carried frequent gene mutations suppressing cell adhesion. These results reveal the multi-omics landscapes determining prognoses of stage II-III CRC patients receiving 5-FU-based chemotherapy.
直到最近，很少有针对接受基于5-氟尿嘧啶（5-FU）化疗的结直肠癌（CRC）患者的预后特征可用于临床实践。在此，我们利用一组癌细胞系的转录谱以及三组CRC患者的数据，为接受基于5-FU化疗的II-III期CRC患者开发了一种基于六个基因对的样本内相对表达顺序（REO）的预后特征。这种基于REO的特征具有独特优势，即对实验批次效应不敏感且无需不切实际的数据标准化要求。使用基于REO的特征将来自癌症基因组图谱的184个具有多组学数据的CRC样本分为两个预后组后，我们进一步发现，高复发风险患者的特征是频繁的基因拷贝数畸变降低了5-FU疗效，以及DNA甲基化畸变诱导了不同的转录变化以赋予5-FU抗性。相比之下，低复发风险患者表现出错配修复缺陷，并携带频繁的抑制细胞粘附的基因突变。这些结果揭示了决定接受基于5-FU化疗的II-III期CRC患者预后的多组学格局。
