Shang Zhihao, Xi Songyang, Lai Yueyang, Cheng Haibo
Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, China.
The First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Front Genet. 2024 Apr 22;15:1357704. doi: 10.3389/fgene.2024.1357704. eCollection 2024.
Colorectal cancer (CRC) is a malignancy with high incidence and mortality rates globally, categorized into left-sided and right-sided CRC, each exhibiting significant differences in molecular characteristics, clinical manifestations, and prognosis. This study employed single-cell transcriptomic data and various bioinformatics approaches, such as two-sample Mendelian randomization, reverse Mendelian randomization, colocalization analysis, directed filtering, pseudotime analysis, and intercellular communication analysis. It analyzed cellular-level disparities between left-sided and right-sided CRC, identifying distinct subpopulations with characteristic variations. For these cells, two-sample Mendelian randomization was utilized to explore gene-to-one-sided CRC causality. LUCAT1 was enriched in high-abundance monocyte subpopulations in right-sided CRC and demonstrated potential risk factor status through Mendelian randomization analysis. The specific single-nucleotide polymorphism (SNP) rs10774624 was associated with an increased risk of CRC. Moreover, metabolic pathway analysis revealed that LUCAT1 monocytes exhibit lower communication activity in the tumor microenvironment and heightened activity in metabolic functions like glycosaminoglycan degradation. Its biological functions are related to the positive regulation of interleukin-6 production and NF-kappa B signaling, among others. This study confirmed a potential causal relationship between LUCAT1 and right-sided CRC risk through Mendelian randomization analysis. These findings provide novel insights into the pathogenesis of right-sided CRC and may aid in developing early detection and treatment strategies for right-sided CRC.
结直肠癌（CRC）是一种在全球范围内发病率和死亡率都很高的恶性肿瘤，分为左侧和右侧CRC，二者在分子特征、临床表现和预后方面均存在显著差异。本研究采用单细胞转录组数据和多种生物信息学方法，如两样本孟德尔随机化、反向孟德尔随机化、共定位分析、定向筛选、伪时间分析和细胞间通讯分析。分析了左侧和右侧CRC在细胞水平上的差异，识别出具有特征性变化的不同亚群。对于这些细胞，利用两样本孟德尔随机化来探究基因与单侧CRC的因果关系。LUCAT1在右侧CRC的高丰度单核细胞亚群中富集，并通过孟德尔随机化分析显示出潜在的危险因素状态。特定的单核苷酸多态性（SNP）rs10774624与CRC风险增加相关。此外，代谢途径分析表明，LUCAT1单核细胞在肿瘤微环境中的通讯活性较低，而在糖胺聚糖降解等代谢功能方面的活性较高。其生物学功能与白细胞介素-6产生和核因子κB信号通路的正调控等有关。本研究通过孟德尔随机化分析证实了LUCAT1与右侧CRC风险之间存在潜在的因果关系。这些发现为右侧CRC的发病机制提供了新的见解，并可能有助于制定右侧CRC的早期检测和治疗策略。
