Zeng Longjin, Chen Xu, Zhang Longyao, Qi Yaxian, Li Lingchen, Yin Chenrui, Sun Jianguo
Department of Basic Medicine, Army Medical University, Chongqing, 400038, China.
Department of Medical Affairs, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
BMC Res Notes. 2025 Jul 22;18(1):314. doi: 10.1186/s13104-025-07324-x.
Weight loss is a firmly established negative survival factor for individuals with cancer, yet effective biomarkers and targeted therapies remain elusive. In this study, we collected skeletal muscle, noncancerous, and cancerous tissues using the Illumina EPIC array to identify conserved DNA methylation probes associated with weight loss following bariatric surgery. Next, the consistency of the probes is evaluated and then the probes are integrated into a generalizable pathway enrichment score. Our results emphasize the gene-centered design, identifying KCNB1, PEAK1, SCG5, and TNIK as key targets of DNA methylation, as confirmed by mouse phenotype data and druggability resources. Moreover, an illustrative test of protein abundance in cell lines is conducted. Utilizing the Clinical Proteomic Tumor Analysis Consortium data, a positive correlation is established between the chromosomal instability scores and our generated score in tumor tissues. In addition, considering these correlation findings, the presence of identifiable methylation blocks in the co-occurring gain samples. Our findings also suggest that upstream molecular drivers may influence this pathway enrichment score, potentially leading to dysregulated methylation associated with weight loss. In summary, DNA methylation analysis not only identifies functional targets but also uncovers new gene-disease connections.
体重减轻是癌症患者公认的不良生存因素，但有效的生物标志物和靶向治疗方法仍然难以捉摸。在本研究中，我们使用Illumina EPIC阵列收集骨骼肌、非癌组织和癌组织，以鉴定与减肥手术后体重减轻相关的保守DNA甲基化探针。接下来，评估探针的一致性，然后将探针整合到一个可推广的通路富集评分中。我们的结果强调了以基因为中心的设计，确定KCNB1、PEAK1、SCG5和TNIK为DNA甲基化的关键靶点，小鼠表型数据和药物可及性资源证实了这一点。此外，还对细胞系中的蛋白质丰度进行了示例性测试。利用临床蛋白质组肿瘤分析联盟的数据，在肿瘤组织中建立了染色体不稳定性评分与我们生成的评分之间的正相关。此外，考虑到这些相关性发现，在同时出现的增益样本中存在可识别的甲基化块。我们的研究结果还表明，上游分子驱动因素可能会影响这一通路富集评分，可能导致与体重减轻相关的甲基化失调。总之，DNA甲基化分析不仅能识别功能靶点，还能揭示新的基因与疾病的联系。
