Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
Department of Head and Neck Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Anal Chem. 2024 Apr 16;96(15):5735-5740. doi: 10.1021/acs.analchem.4c00306. Epub 2024 Apr 3.
Lipid metabolic alterations are known to play a crucial role in cancer metastasis. As a key hub in lipid metabolism, intracellular neutral lipid accumulation in lipid droplets (LDs) has become a signature of aggressive human cancers. Nevertheless, it remains unclear whether lipid accumulation displays distinctive features in metastatic lesions compared to the primary ones. Here, we integrated multicolor stimulated Raman scattering (SRS) imaging with confocal Raman spectroscopy on the same platform to quantitatively analyze the amount and composition of LDs in intact human thyroid tissues without any processing or labeling. Inspiringly, we found aberrant accumulation of triglycerides (TGs) in lymphatic metastases but not in normal thyroid, primary papillary thyroid carcinoma (PTC), or normal lymph node. In addition, the unsaturation degree of unsaturated TGs was significantly higher in the lymphatic metastases from patients diagnosed with late-stage (T3/T4) PTC compared to those of patients diagnosed with early-stage (T1/T2) PTC. Furthermore, both public sequencing data analysis and our RNA-seq transcriptomic experiment showed significantly higher expression of alcohol dehydrogenase-1B (ADH1B), which is critical to lipid uptake and transport, in lymphatic metastases relative to the primary ones. In summary, these findings unravel the lipid accumulation as a novel marker and therapeutic target for PTC lymphatic metastasis that has a poor response to the regular radioactive iodine therapy.
脂质代谢改变被认为在癌症转移中起着至关重要的作用。作为脂质代谢的关键枢纽，细胞内中性脂质在脂滴（LDs）中的积累已成为侵袭性人类癌症的特征。然而，脂质积累在转移病灶与原发性病灶之间是否具有独特的特征仍不清楚。在这里，我们整合了多色受激拉曼散射（SRS）成像和共聚焦拉曼光谱，在同一平台上对未经任何处理或标记的完整人甲状腺组织中的 LD 的数量和组成进行定量分析。令人鼓舞的是，我们发现淋巴转移中存在异常的甘油三酯（TG）积累，但在正常甲状腺、原发性甲状腺乳头状癌（PTC）或正常淋巴结中不存在。此外，与早期（T1/T2）PTC 患者相比，晚期（T3/T4）PTC 患者的淋巴转移中不饱和 TG 的不饱和程度明显更高。此外，公共测序数据分析和我们的 RNA-seq 转录组实验均显示，在淋巴转移中，对脂质摄取和转运至关重要的醇脱氢酶-1B（ADH1B）的表达明显高于原发性病灶。总之，这些发现揭示了脂质积累作为 PTC 淋巴转移的一个新的标志物和治疗靶点，而后者对常规放射性碘治疗的反应较差。
