Zhang Cong, Shi Dan, Lai Guichuan, Li Kangjie, Zhang Yuan, Li Wenlong, Zeng Haijiao, Yan Qiaoping, Zhong Xiaoni, Xie Biao
Department of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing, 400016, China.
Department of Nutrition and Food Hygiene, School of Public Health, Chongqing Medical University, Chongqing, China.
Arch Toxicol. 2025 Feb;99(2):645-665. doi: 10.1007/s00204-024-03910-3. Epub 2024 Dec 16.
An abundant amount of colon cancers is diagnosed every year, accounting for 9% of malignant tumors. Even with the progress of relevant research, the 5-year survival rate for colon cancer is still less than 60%, indicating that improving the prognosis of colon cancer is still a challenge that needs to be overcome. This study employed the algorithm "scissor" to integrate the single-cell sequencing data and bulk transcriptome data with prognosis information to predict prognosis-associated cells (PAC). Summary-data-based Mendelian randomization (SMR) analysis was conducted using expression quantitative trait loci data and GWAS data to identify genes having causal associations with prognosis phenotype in colon cancer patients and five traditional two-sample Mendelian randomization methods were utilized to confirm the results. Finally, our findings were validated based on two independent external validation datasets, GSE17536 and GSE39582. The real-world tissue dataset with corresponding immunohistochemical (IHC) experiments was utilized to confirm our findings. We determined that the majority of PACs were fibroblasts. On top of that, this study identified ADAMDEC1 as a gene that has a significant causal association with overall survival. ADAMDEC1, highly expressed in highly differentiated fibroblasts, was ascertained its high expression was linked with a better prognosis of patients with colon cancer by the related bulk transcriptome analysis. Our dataset presented that higher IHC scores were associated with a better prognosis for colon cancer, further validating our results. This study has identified ADAMDEC1 as a prognostic protective factor for patients with colon cancer, providing clues for clinical trials and drug experimental target research.
每年都会诊断出大量结肠癌病例，占恶性肿瘤的9%。即使相关研究取得了进展，结肠癌的5年生存率仍低于60%，这表明改善结肠癌的预后仍然是一个需要克服的挑战。本研究采用“scissor”算法，将单细胞测序数据和批量转录组数据与预后信息整合起来，以预测预后相关细胞（PAC）。利用表达数量性状位点数据和全基因组关联研究（GWAS）数据进行基于汇总数据的孟德尔随机化（SMR）分析，以识别与结肠癌患者预后表型具有因果关联的基因，并使用五种传统的两样本孟德尔随机化方法来验证结果。最后，我们的研究结果在两个独立的外部验证数据集GSE17536和GSE39582上得到了验证。利用具有相应免疫组织化学（IHC）实验的真实世界组织数据集来证实我们的研究结果。我们确定大多数PAC是成纤维细胞。除此之外，本研究确定ADAMDEC1是一个与总生存期具有显著因果关联的基因。通过相关的批量转录组分析确定，ADAMDEC1在高分化成纤维细胞中高表达，其高表达与结肠癌患者的较好预后相关。我们的数据集表明，较高的IHC评分与结肠癌的较好预后相关，进一步验证了我们的结果。本研究已确定ADAMDEC1是结肠癌患者的预后保护因子，为临床试验和药物实验靶点研究提供了线索。
