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Abstract：
Competitive endogenous RNAs (ceRNAs) and tumor-infiltrating immune cells play essential roles in colorectal cancer (CRC) tumorigenesis. However, their prognostic role in elderly patients with CRC is unclear. Gene expression profiles and clinical information for elderly patients with CRC were downloaded from The Cancer Genome Atlas. Univariate, LASSO, and multivariate Cox regression analyses were utilized for screening key ceRNAs and prevent overfitting. A total of 265 elderly patients with CRC were included. We constructed a novel ceRNA network consisting of 17 lncRNAs, 35 miRNAs, and 5 mRNAs. We established three prognosis predictive nomograms based on four key ceRNAs (ceRNA nomogram), five key immune cells (immune cell nomogram), and their combination (ceRNA-immune cell nomogram). Among them, the ceRNA-immune cell nomogram had the best accuracy. Furthermore, the areas under the curve of the ceRNA-immune cell nomogram were also significantly greater than the TNM stage at 1 (0.818 vs. 0.693), 3 (0.865 vs. 0.674), and 5 (0.832 vs. 0.627) years. Co-expression analysis revealed that CBX6 was positively correlated with activated dendritic cells (R = 0.45, p < 0.01), whereas negatively correlated with activated mast cells (R =- 0.43, p < 0.01). In conclusion, our study constructed three nomograms to predict prognosis in elderly patients with CRC, among which the ceRNA-immune cell nomogram had the best prediction accuracy. We inferred that the mechanism underlying the regulation of activated dendritic cells and mast cells by CBX6 might play a crucial role in tumor development and prognosis of elderly patients with CRC.
摘要：
竞争性内源性RNA（ceRNA）和肿瘤浸润免疫细胞在结直肠癌（CRC）肿瘤发生中起着至关重要的作用。然而,其在老年CRC患者中的预后作用尚不清楚.从癌症基因组图谱下载老年CRC患者的基因表达谱和临床信息。单变量,拉索,和多变量Cox回归分析用于筛选关键ceRNA并防止过拟合。共纳入265例老年CRC患者。我们构建了一个由17个lncRNAs组成的新型ceRNA网络，35个miRNAs,和5个mRNA。我们基于四个关键的ceRNA（ceRNA列线图）建立了三个预后预测列线图，五个关键免疫细胞（免疫细胞列线图），和它们的组合（ceRNA-免疫细胞列线图）。其中,ceRNA免疫细胞列线图的准确性最好。此外，ceRNA-免疫细胞列线图的曲线下面积也显著大于1时的TNM分期(0.818vs.0.693),3（0.865vs.0.674),和5（0.832vs.0.627）年。共表达分析显示CBX6与活化的树突状细胞呈正相关(R=0.45,p<0.01),而与激活的肥大细胞呈负相关（R=-0.43，p<0.01）。总之,我们的研究构建了三个列线图来预测老年CRC患者的预后，其中，ceRNA-免疫细胞列线图具有最好的预测准确性。我们推测，CBX6对活化的树突状细胞和肥大细胞的调节机制可能在老年CRC患者的肿瘤发展和预后中起着至关重要的作用。
