Bjelanović Jasna, Nikolić Aleksandra, Aslan Mutay, Miladinov Marko, Kotur Nikola, Barišić Goran, Dragicević Sandra
University Clinical Center of Serbia, Center for Medical Biochemistry, Belgrade.
University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Belgrade.
J Med Biochem. 2025 Jun 13;44(3):524-533. doi: 10.5937/jomb0-55113.
Altered sphingolipid levels might contribute to rectal cancer development, progression and therapy response by regulating various biological processes, including apoptosis. This study aimed to analyse the serum sphingolipid profile in rectal cancer patients and investigate its association with the apoptotic status of tumour tissue and therapy response.
Ceramide (CER) and sphingomyelin (SM) serum levels were analysed in 22 patients with locally advanced rectal cancer and 24 healthy individuals by ultrafast liquid chromatography coupled with tandem mass spectrometry. The expression of pro-apoptotic BAX (BCL2 associated X, apoptosis regulator) and anti-apoptotic BCL2 (BCL2 apoptosis regulator) was analysed in tumour and corresponding healthy tissue samples of patients by quantitative real-time PCR.
Significantly lower serum levels of C18 CER, C22 CER, C24 CER, C18 SM and C24 SM were observed in patients than in controls (P<0.05). For C20 CER, C22 CER and C24 CER, a positive correlation with the pro-apoptotic status of tumour tissue was found (r=0.619, P=0.018; r=0.694, P=0.006 and r=0.601, P=0.023, respectively). No difference in serum sphingolipid levels was found between patients with good, moderate, and poor responses to therapy.
These results support the involvement of sphingolipids in rectal cancer. However, further studies, including a larger cohort of subjects, are needed to clarify the association of sphingolipid metabolites with therapy response.
鞘脂水平的改变可能通过调节包括细胞凋亡在内的各种生物学过程，促进直肠癌的发生、发展及治疗反应。本研究旨在分析直肠癌患者血清鞘脂谱，并探讨其与肿瘤组织凋亡状态及治疗反应的关系。
采用超快速液相色谱-串联质谱法分析22例局部晚期直肠癌患者和24例健康个体血清中神经酰胺（CER）和鞘磷脂（SM）水平。通过定量实时PCR分析患者肿瘤及相应健康组织样本中促凋亡蛋白BAX（BCL2相关X蛋白，凋亡调节因子）和抗凋亡蛋白BCL2（BCL2凋亡调节因子）的表达。
患者血清中C18 CER、C22 CER、C24 CER、C18 SM和C24 SM水平显著低于对照组（P<0.05）。对于C20 CER、C22 CER和C24 CER，发现其与肿瘤组织的促凋亡状态呈正相关（r分别为0.619，P=0.018；r=0.694，P=0.006；r=0.601，P=0.023）。治疗反应良好、中等和较差的患者血清鞘脂水平无差异。
这些结果支持鞘脂参与直肠癌的发生发展。然而，需要进一步研究，包括纳入更大样本量的队列，以阐明鞘脂代谢产物与治疗反应的关系。
