收稿日期: 2025-03-05
网络出版日期: 2025-06-19
基金资助
国家自然科学基金青年项目(82205109);湖北民族大学2024年研究生科研创新项目(MYK2024087);湖北民族大学风湿性疾病发生与干预湖北省重点实验室项目(PT022402);广州市科技局基础与应用基础研究项目(2025A04J3690);广州中医药大学第一附属医院中青年骨干培育项目(09005650055)
Lipidomic profile of serum in colorectal cancer patients and its diagnostic significance
Received date: 2025-03-05
Online published: 2025-06-19
目的 探讨结直肠癌患者的血清脂质代谢特点及其诊断价值。 方法 采用超高效液相色谱-飞行时间质谱技术结合主成分分析(PCA分析)、正交偏最小二乘判别分析(OPLS-DA分析)对57例结直肠癌患者和54例健康志愿者的血清样本进行脂质组学分析。以P < 0.05,VIP值 > 1,差异倍数< 0.67或> 1.5为标准筛选差异脂质。对差异脂质进行受试者工作特征曲线(ROC)分析,筛选出具有良好诊断价值的差异脂质作为生物标志物。 结果 共筛选出5类、66种差异脂质,其中磷脂酰胆碱(PC)和甘油三酯(TG)占比高达59.09%,KEGG通路富集主要涉及甘油磷脂代谢及甘油酯代谢途径。ROC分析筛选Sphinganine、MG(19∶0)、LysoPC(18∶2)、PA(42∶6)、PC(36∶5)、PC(36∶4)、PC(38∶6)、PC(40∶8)的曲线下面积大于0.85。 结论 通过UPLC-Q/TOF-MS技术并运用改良的Bligh-Dyer法高效富集血清中的脂质类代谢物,能较为系统地分析CRC患者的脂质代谢轮廓。筛选出的Sphinganine、MG(19∶0)、LysoPC(18∶2)、PA(42∶6)、PC(36∶5)、PC(36∶4)、PC(38∶6)、PC(40∶8)等8种脂质可以为区分健康志愿者和结直肠癌患者提供新的视角和参数。
关键词: 结直肠癌; 超高效液相色谱-飞行时间质谱; 脂质组学; 早期筛查; 生物标志物
杨潇 , 王涛 , 王伟 , 彭耀辉 , 陈妍 , 曾海平 , 杨宝 . 结直肠癌患者的血清脂质组学特点及其诊断价值[J]. 实用医学杂志, 2025 , 41(11) : 1742 -1750 . DOI: 10.3969/j.issn.1006-5725.2025.11.020
Objective This study examines serum lipid metabolism characteristics in colorectal cancer patients and its diagnostic potential. Methods Serum samples from 57 colorectal cancer patients and 54 healthy controls underwent lipidomic analysis using ultra-high performance liquid chromatography-time-of-flight mass spectrometry, combined with principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) . Differential lipids were identified based on criteria of P< 0.05, VIP > 1, and fold change < 0.67 or > 1.5. These lipids were further evaluated using receiver operating characteristic (ROC) analysis to identify biomarkers with strong diagnostic value. Results Five classes and 66 differential lipids were identified, with phosphatidylcholine (PC) and triglyceride (TG) comprising 59.09%. KEGG pathway enrichment indicated involvement in glycerophospholipid and glycerol ester metabolism pathways. ROC analysis identified Sphinganine, MG(19∶0), LysoPC(18∶2), PA(42∶6), PC(36∶5), PC(36∶4), PC(38∶6), and PC(40∶8) as having areas under the curve greater than 0.85. Conclusion The lipid metabolic profile of colorectal cancer (CRC) patients can be systematically analyzed through the efficient enrichment of lipid metabolites in serum using the UPLC-Q/TOF-MS technique, in conjunction with a modified Bligh-Dyer method. The identification of eight specific lipids including Sphinganine, MG(19∶0), LysoPC(18∶2), PA(42∶6), PC(36∶5), PC(36∶4), PC(38∶6), and PC(40∶8) offer novel insights and parameters for differentiating between healthy individuals and those diagnosed with colorectal cancer.
| 1 | SIEGEL R L, GIAQUINTO A N, JEMAL A. Cancer statistics, 2024[J]. CA Cancer J Clin, 2024, 74(1): 12-49. doi:10.3322/caac.21820 |
| 2 | QU R, MA Y, ZHANG Z, et al. Increasing burden of colorectal cancer in China[J]. Lancet Gastroenterol Hepatol, 2022, 7(8): 700. doi:10.1016/s2468-1253(22)00156-x |
| 3 | LADABAUM U, DOMINITZ J A, KAHI C, et al. Strategies for colorectal cancer screening[J]. Gastroenterology, 2020, 158(2): 418-432. doi:10.1053/j.gastro.2019.06.043 |
| 4 | 朱吉玥, 张波, 李亚茹, 等. 全身炎症反应指数对早期结直肠癌内镜黏膜下剥离术后非治愈性切除的预测价值[J]. 实用医学杂志, 2025, 41(5): 716-723. |
| 5 | HEUSCHMID M, LUZ O, SCHAEFER J F, et al. Computed tomographic colonography (CTC): Possibilities and limitations of clinical application in colorectal polyps and cancer[J]. Technol Cancer Res Treat, 2004, 3(2): 201-207. doi:10.1177/153303460400300213 |
| 6 | ZHONG J, GUO J, ZHANG X, et al. The remodeling roles of lipid metabolism in colorectal cancer cells and immune microenvironment[J]. Oncol Res, 2022, 30(5): 231-242. doi:10.32604/or.2022.027900 |
| 7 | STEVANOVIC M, VEKIC J, BOGAVAC-STANOJEVIC N, et al. Significance of LDL and HDL subclasses characterization in the assessment of risk for colorectal cancer development[J]. Biochem Med, 2018, 28(3): 030703. doi:10.11613/bm.2018.030713 |
| 8 | DU M, GU D, XIN J, et al. Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer[J]. Cell Rep Med, 2023, 4(3): 100974. doi:10.1016/j.xcrm.2023.100974 |
| 9 | ZHANG S L, CHENG L S, ZHANG Z Y, et al. Untangling determinants of gut microbiota and tumor immunologic status through a multi-omics approach in colorectal cancer[J]. Pharmacol Res, 2023, 188: 106633. doi:10.1016/j.phrs.2022.106633 |
| 10 | CLOS-GARCIA M, GARCIA K, ALONSO C, et al. Integrative Analysis of Fecal Metagenomics and Metabolomics in Colorectal Cancer[J]. Cancers, 2020, 12(5): 1142. doi:10.3390/cancers12051142 |
| 11 | 王佳慧, 郑可, 李雪梅. 脂质组学在肾脏疾病中的应用与进展[J]. 实用医学杂志, 2025, 41(1): 1-6. |
| 12 | ZHANG L, ZHU B, ZENG Y, et al. Clinical lipidomics in understanding of lung cancer: Opportunity and challenge[J]. Cancer Lett, 2020, 470: 75-83. doi:10.1016/j.canlet.2019.08.014 |
| 13 | TAKANASHI Y, KAHYO T, SEKIHARA K, et al. Prognostic potential of lipid profiling in cancer patients: A systematic review of mass spectrometry-based studies[J]. Lipids Health Dis, 2024, 23(1): 154. doi:10.1186/s12944-024-02121-0 |
| 14 | WOLRAB D, JIRáSKO R, CíFKOVá E, et al. Lipidomic profiling of human serum enables detection of pancreatic cancer[J]. Nat Commun, 2022, 13(1): 124. doi:10.1038/s41467-021-27765-9 |
| 15 | 刘锦燕, 郑彧鸣, 曹祎婕, 等. 结直肠癌诊断性生物标志物的研究进展[J]. 标记免疫分析与临床, 2022, 29(9): 1592-1596. |
| 16 | LECH G, S?OTWI?SKI R, S?ODKOWSKI M, et al. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances[J]. World J Gastroenterol, 2016, 22(5): 1745-1755. doi:10.3748/wjg.v22.i5.1745 |
| 17 | HOSSAIN M S, KARUNIAWATI H, JAIROUN A A, et al. Colorectal cancer: A review of carcinogenesis, global epidemiology, current challenges, risk factors, preventive and treatment strategies[J]. Cancers, 2022, 14(7): 1732. doi:10.3390/cancers14071732 |
| 18 | 杨宝, 梁运啸, 黄宗声, 等. 基于超高效液相色谱-四极杆-静电场轨道阱质谱的结直肠腺瘤患者血清代谢组学研究[J]. 分析测试学报, 2022, 41(5): 668-674. |
| 19 | OSAWA T, FUJIKAWA K, SHIMAMOTO K. Structures, functions, and syntheses of glycero-glycophospholipids[J]. Front Chem, 2024, 12: 1353688. doi:10.3389/fchem.2024.1353688 |
| 20 | WANG Z, YANG M, YANG Y, et al. Structural basis for catalysis of human choline/ethanolamine phosphotransferase 1[J]. Nat Commun, 2023, 14(1): 2529. doi:10.1038/s41467-023-38290-2 |
| 21 | STOICA C, FERREIRA A K, HANNAN K, et al. Bilayer forming phospholipids as targets for cancer therapy[J]. Int J Mol Sci, 2022, 23(9): 5266. doi:10.3390/ijms23095266 |
| 22 | ZECHNER R, ZIMMERMANN R, EICHMANN T O, et al. FAT SIGNALS--lipases and lipolysis in lipid metabolism and signaling[J]. Cell Metab, 2012, 15(3): 279-291. doi:10.1016/j.cmet.2011.12.018 |
| 23 | ZHANG X, SAARINEN A M, HITOSUGI T, et al. Inhibition of intracellular lipolysis promotes human cancer cell adaptation to hypoxia[J]. eLife, 2017, 6: e31132. doi:10.7554/elife.31132 |
| 24 | CHUNG Y W, HAN D S, PARK Y K, et al. Association of obesity, serum glucose and lipids with the risk of advanced colorectal adenoma and cancer: A case-control study in korea[J]. Dig Liver Dis, 2006, 38(9): 668-672. doi:10.1016/j.dld.2006.05.014 |
| 25 | CANALS D, PERRY D M, JENKINS R W, et al. Drug targeting of sphingolipid metabolism: Sphingomyelinases and ceramidases[J]. Br J Pharmacol, 2011, 163(4): 694-712. doi:10.1111/j.1476-5381.2011.01279.x |
| 26 | MARKOWSKI A R, B?ACHNIO-ZABIELSKA A U, POGODZI?SKA K, et al. Diverse sphingolipid profiles in rectal and colon cancer[J]. Int J Mol Sci, 2023, 24(13): 10867. doi:10.3390/ijms241310867 |
| 27 | SUN R, GU J, CHANG X, et al. Metabonomics study on orthotopic transplantion mice model of colon cancer treated with astragalus membranaceus-curcuma wenyujin in different proportions via UPLC-Q-TOF/MS[J]. J Pharm Biomed Anal, 2021, 193: 113708. doi:10.1016/j.jpba.2020.113708 |
| 28 | FHU C W, ALI A. Fatty acid synthase: An emerging target in cancer[J]. Molecules, 2020, 25(17): 3935. doi:10.3390/molecules25173935 |
| 29 | RUTTER M, SAUNDERS B, WILKINSON K, et al. Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis[J]. Gastroenterology, 2004, 126(2): 451-459. doi:10.1053/j.gastro.2003.11.010 |
| 30 | MARTIN-PEREZ M, URDIROZ-URRICELQUI U, BIGAS C, et al. The role of lipids in cancer progression and metastasis[J]. Cell Metab, 2022, 34(11): 1675-1699. doi:10.1016/j.cmet.2022.09.023 |
| 31 | CHANG J, TANG N, FANG Q, et al. Inhibition of COX-2 and 5-LOX regulates the progression of colorectal cancer by promoting PTEN and suppressing PI3K/AKT pathway[J]. Biochem Biophys Res Commun, 2019, 517(1): 1-7. doi:10.1016/j.bbrc.2018.01.061 |
| 32 | YANG K, LI H, DONG J, et al. Expression profile of polyunsaturated fatty acids in colorectal cancer[J]. World J Gastroenterol, 2015, 21(8): 2405-2412. doi:10.3748/wjg.v21.i8.2405 |
| 33 | 林泽帅, 晏涛, 陈佳妮, 等. 尿液非极性代谢物中筛选结直肠癌诊断与化疗毒性标志物[J]. 中国医药导刊, 2022, 24(2): 131-139. |
| 34 | ECKER J, BENEDETTI E, KINDT A S D, et al. The colorectal cancer lipidome: identification of a robust tumor-specific lipid species signature[J]. Gastroenterology, 2021, 161(3): 910-923.e19. doi:10.1053/j.gastro.2021.05.009 |
/
| 〈 |
|
〉 |