Department of the First Surgery, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China.
IUBMB Life. 2019 Nov;71(11):1760-1770. doi: 10.1002/iub.2124. Epub 2019 Jul 13.
Immune infiltration of tumors has been increasingly accepted as a prognostic factor in colon cancer. Here, we aim to develop a novel immune signature, based on estimated immune landscape from tumor transcriptomes, to predict the overall survival of patients with colon cancer. The compositions of 22 immune cell subtypes from three microarray datasets were characterized with the CIBERSORT deconvolution algorithm. A prognostic immunoscore (PIS) model for overall survival prediction was established by using least absolute shrinkage and selection operator (LASSO) penalized regression analysis. A total of 17 immune cell markers were screened out in the LASSO model and were then aggregated to generate the PIS. In the training cohort (n = 490), patients with high PIS exhibited a remarkably poorer overall survival than those with low PIS. Similar results were obtained in patients with different TNM stages and in patients receiving adjunctive chemotherapy or not. Multivariate Cox regression indicated that the PIS was an independent predictor for overall survival in colon cancer (hazard ratio: 2.734, 95% confidence interval: 2.052-3.643, p < .001). The prognostic capability of PIS was also confirmed in the testing cohort (n = 245) and the entire cohort (n = 735). As for biological implications, the PIS was significantly associated with some immune checkpoints, inflammatory factors, epithelial-mesenchymal transformation regulators, and many known signaling pathways in cancer. The results of our study provide a novel and promising immune signature for overall survival prediction of patients with colon cancer.
肿瘤的免疫浸润已被越来越多地认为是结肠癌的预后因素。在这里，我们旨在基于肿瘤转录组估计的免疫景观，开发一种新的免疫特征，以预测结肠癌患者的总生存率。使用 CIBERSORT 去卷积算法对来自三个微阵列数据集的 22 种免疫细胞亚型的组成进行了表征。通过使用最小绝对收缩和选择算子 (LASSO) 惩罚回归分析建立了用于总体生存预测的预后免疫评分 (PIS) 模型。在 LASSO 模型中筛选出 17 个免疫细胞标记物，并将其聚集以生成 PIS。在训练队列 (n = 490) 中，PIS 高的患者总生存率明显低于 PIS 低的患者。在不同 TNM 分期的患者和接受辅助化疗或不接受辅助化疗的患者中也得到了类似的结果。多变量 Cox 回归表明，PIS 是结肠癌总生存的独立预测因子 (危险比：2.734，95%置信区间：2.052-3.643，p < 0.001)。PIS 的预后能力也在测试队列 (n = 245) 和整个队列 (n = 735) 中得到了证实。就生物学意义而言，PIS 与一些免疫检查点、炎症因子、上皮-间充质转化调节剂以及癌症中的许多已知信号通路显著相关。我们的研究结果为预测结肠癌患者的总体生存率提供了一种新的、有前途的免疫特征。
