Liu Han-Xuan, Feng Jie, Jiang Jing-Jing, Shen Wan-Jun, Zheng Yu, Liu Gang, Gao Xiang-Yang
Beijing Jinghua Anliang Technology, Beijing 102627, China.
Department of Clinical Laboratory, The First Medical Centre of Chinese PLA General Hospital, Beijing 100853, China.
World J Gastrointest Oncol. 2024 Jul 15;16(7):3032-3054. doi: 10.4251/wjgo.v16.i7.3032.
Colorectal cancer (CRC) prognosis prediction is currently a major challenge. Epigenetic regulation has been widely reported for its role in cancer development.
To construct a robust prognostic signature, we used developed and validated across datasets.
After constructing the signature, the prognostic value of the signature was evaluated in the TCGA cohort and six independent datasets (GSE17526, GSE17537, GSE33113, GSE37892, GSE39048 and GSE39582). The clinical, genomic and transcriptomic features related to the signature were identified. The correlations of the signature score with immune cell infiltration and cell-cell interactions were analyzed. The correlations between the signature score and the sensitivity to different drugs were also predicted.
In the TCGA cohort, patients in the low-risk group according to the signature score had longer survival than those in the high-risk group, and this finding was validated in the validation datasets. The signature was a prognostic factor independent of age and sex and was correlated with stage and / expression. Area under the receiving operating characteristic curve was 0.72. Genomic association analyses revealed that samples from high-risk patients exhibited chromosomal instability. Transcriptomic analyses revealed that the signature score was significantly associated with multiple cellular pathways. Bulk RNA-seq and single-cell sequencing data revealed that the signature reflected differences in infiltrating immune cell-tumor cell interactions, especially for macrophages. The signature also predicted the putative drug sensitivity of CRC samples.
The signature is a valuable biomarker for predicting CRC prognosis and reflects multiple features of CRC, especially macrophage infiltration in the microenvironment.
结直肠癌（CRC）预后预测目前是一项重大挑战。表观遗传调控在癌症发展中的作用已被广泛报道。
为构建一个可靠的预后特征，我们在多个数据集上进行开发和验证。
构建特征后，在TCGA队列和六个独立数据集（GSE17526、GSE17537、GSE33113、GSE37892、GSE39048和GSE39582）中评估该特征的预后价值。确定与该特征相关的临床、基因组和转录组特征。分析特征评分与免疫细胞浸润和细胞间相互作用的相关性。还预测了特征评分与对不同药物敏感性之间的相关性。
在TCGA队列中，根据特征评分划分的低风险组患者的生存期比高风险组患者长，这一发现在验证数据集中得到了验证。该特征是一个独立于年龄和性别的预后因素，与分期和/表达相关。受试者工作特征曲线下面积为0.72。基因组关联分析显示，高风险患者的样本表现出染色体不稳定。转录组分析显示，特征评分与多个细胞通路显著相关。批量RNA测序和单细胞测序数据显示，该特征反映了浸润免疫细胞与肿瘤细胞相互作用的差异，尤其是巨噬细胞。该特征还预测了CRC样本的推定药物敏感性。
该特征是预测CRC预后的有价值生物标志物，反映了CRC的多个特征，尤其是微环境中的巨噬细胞浸润。
