Department of Radiotherapy, The Second Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China.
Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China.
Cancer Biother Radiopharm. 2024 Nov;39(9):673-689. doi: 10.1089/cbr.2023.0181. Epub 2024 Aug 19.
Colorectal cancer (CRC) is a major global health challenge with a need for new biomarkers and therapeutic targets. This work investigated the biological mechanisms and clinical value of Ly1 antibody reactive (LYAR) in CRC. We analyzed LYAR mRNA expression across multiple public databases, including genotype-tissue expression, gene expression omnibus, Oncomine, and the cancer genome atlas, alongside in-house immunohistochemical data to evaluate LYAR protein expression in CRC and non-CRC colorectal tissues. Gene set enrichment analysis (GSEA) was used to elucidate LYAR's biological functions, and its impact on the tumor immune microenvironment was assessed using CIBERSORT, ESTIMATE, and single-cell RNA sequencing techniques. In addition, LYAR's association with clinicopathological features and patient prognosis was explored, and its influence on drug sensitivity was investigated using the Connectivity Map database. LYAR was significantly upregulated in CRC tissues compared with non-CRC colorectal counterparts, associated with altered immune cell composition and enhanced RNA processing, splicing, and cell cycle regulation. High LYAR expression correlated with poor disease-free and overall survival, underscoring its prognostic value. GSEA revealed LYAR's involvement in critical cellular processes and pathways, including DNA repair, cell cycle, and mTORC1 signaling. Correlation analysis identified genes positively and negatively associated with LYAR, leading to the discovery of temsirolimus and WYE-354, mTOR inhibitors, as potential therapeutic agents for CRC. Furthermore, LYAR expression predicted increased sensitivity to cetuximab in RAS wild-type metastatic CRC, indicating its utility as a biomarker for treatment responsiveness. LYAR's upregulation in CRC highlights its potential as a biomarker for prognosis and therapeutic targeting, offering insights into CRC pathology and suggesting new avenues for treatment optimization.
结直肠癌（CRC）是一个全球性的重大健康挑战，需要新的生物标志物和治疗靶点。本研究旨在探讨 Ly1 抗体反应性（LYAR）在 CRC 中的生物学机制和临床价值。我们分析了多个公共数据库中的 LYAR mRNA 表达，包括基因型组织表达、基因表达综合数据库、Oncomine 和癌症基因组图谱，以及内部免疫组织化学数据，以评估 LYAR 在 CRC 和非 CRC 结直肠组织中的蛋白表达。基因集富集分析（GSEA）用于阐明 LYAR 的生物学功能，并使用 CIBERSORT、ESTIMATE 和单细胞 RNA 测序技术评估其对肿瘤免疫微环境的影响。此外，还探讨了 LYAR 与临床病理特征和患者预后的关系，并使用 Connectivity Map 数据库研究了其对药物敏感性的影响。与非 CRC 结直肠组织相比，CRC 组织中 LYAR 表达显著上调，与免疫细胞组成改变和 RNA 加工、剪接和细胞周期调控增强相关。高 LYAR 表达与无病生存和总生存不良相关，凸显了其预后价值。GSEA 显示 LYAR 参与了关键的细胞过程和途径，包括 DNA 修复、细胞周期和 mTORC1 信号通路。相关性分析确定了与 LYAR 呈正相关和负相关的基因，从而发现了雷帕霉素和 WYE-354，即 mTOR 抑制剂，作为 CRC 的潜在治疗药物。此外，LYAR 表达预测 RAS 野生型转移性 CRC 对西妥昔单抗的敏感性增加，表明其作为治疗反应性生物标志物的潜力。CRC 中 LYAR 的上调突出了其作为预后和治疗靶点的潜力，为 CRC 病理学提供了新的见解，并为治疗优化提供了新的途径。
