Guo Yongjie, Shen Kailin, Ge Shuqing, Zheng Qi, Gao Jingchao, He Xiaopo
Department of Maxillofacial Surgery, Wei Fang People's Hospital, Wei Fang, China.
Department of Intervention, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Medicine (Baltimore). 2025 Mar 14;104(11):e41802. doi: 10.1097/MD.0000000000041802.
Major salivary gland carcinomas (MSGCs) is a rare but aggressive cancer, with limited understanding of its metabolic underpinnings. Lipid metabolism, particularly fatty acid metabolism ratios (FAMRs), has been implicated in various cancers, but its role in MSGCs remains unclear. This study aims to explore the potential causal relationships between specific FAMRs and MSGCs using Mendelian randomization (MR) analysis. A 2-sample MR analysis was conducted using summary data from genome-wide association studies. Three FAMRs, including the ratio of diacylglycerol to triglycerides (DAG/TG), total cholesterol (TC) to total lipids (TL) ratio in large very low-density lipoprotein (VLDL; TC/TL in large VLDL), and triglycerides to total lipids ratio in medium VLDL (TG/TL in medium VLDL), were investigated for their potential causal relationships with MSGCs. Sensitivity analyses, including MR-Egger and leave-one-out tests, were performed to assess pleiotropy and the robustness of the results. The DAG/TG and TC/TL ratios in large VLDL were significantly positively associated with an increased risk of MSGCs (OR = 10.921, P = .004 and OR = 2.651, P = .047, respectively). In contrast, the TG/TL ratio in medium VLDL showed a significant negative association with MSGCs risk (OR = 0.460, P = .041). Sensitivity analyses confirmed the robustness of these associations, with no evidence of significant pleiotropy in 2 of the ratios. This study reveals novel insights into the metabolic basis of MSGCs, demonstrating significant associations between specific FAMRs and MSGCs risk. These findings highlight the potential clinical relevance of FAMRs as biomarkers or therapeutic targets in MSGCs. Future studies should focus on diverse populations and mechanistic research to validate these associations and explore their clinical implications.
大唾液腺癌（MSGCs）是一种罕见但侵袭性强的癌症，人们对其代谢基础的了解有限。脂质代谢，特别是脂肪酸代谢比率（FAMRs），已被认为与多种癌症有关，但其在MSGCs中的作用仍不清楚。本研究旨在使用孟德尔随机化（MR）分析来探索特定FAMRs与MSGCs之间潜在的因果关系。使用全基因组关联研究的汇总数据进行了两样本MR分析。研究了三种FAMRs，包括二酰甘油与甘油三酯的比率（DAG/TG）、大极低密度脂蛋白（VLDL）中总胆固醇（TC）与总脂质（TL）的比率（大VLDL中的TC/TL）以及中VLDL中甘油三酯与总脂质的比率（中VLDL中的TG/TL）与MSGCs的潜在因果关系。进行了敏感性分析，包括MR-Egger检验和留一法检验，以评估多效性和结果的稳健性。大VLDL中的DAG/TG和TC/TL比率与MSGCs风险增加显著正相关（OR = 10.921，P = 0.004和OR = 2.651，P = 0.047）。相比之下，中VLDL中的TG/TL比率与MSGCs风险呈显著负相关（OR = 0.460，P = 0.041）。敏感性分析证实了这些关联的稳健性，其中两个比率没有显著多效性的证据。本研究揭示了MSGCs代谢基础的新见解，证明了特定FAMRs与MSGCs风险之间的显著关联。这些发现突出了FAMRs作为MSGCs生物标志物或治疗靶点的潜在临床相关性。未来的研究应集中在不同人群和机制研究上，以验证这些关联并探索其临床意义。
