| 张兆雪,姜媛媛,梁烁,等.基于质谱多反应监测技术测定胃癌石蜡切片中CS表达谱信息及其临床意义[J].中国海洋药物,2025,(5):-. |
| 基于质谱多反应监测技术测定胃癌石蜡切片中CS表达谱信息及其临床意义 |
| Analysis of CS expression profile information in paraffin sections of gastric cancer and its clinical significance based on mass spectrometry multiple reaction monitoring technology |
| 投稿时间：2024-03-20 修订日期：2024-06-09 |
| DOI： |
| 中文关键词: 胃癌 石蜡切片 硫酸软骨素 LC-MRM-MS/MS 生物标志物 |
| English Keywords:Gastric cancer CS Paraffin section LC-MRM-MS/MS Biomarkers |
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| 中文摘要: |
| 目的 提取胃癌临床组织中硫酸软骨素(CS)二糖,采用定向酶解和2-AMAC荧光标记等样品前处理方法,结合质谱多反应监测(MRM)技术,准确、高效、超灵敏定量分析福尔马林固定石蜡包埋的胃癌组织中CS表达谱,并探究CS表达谱与患者各项临床指征相关性。方法 通过脱蜡水化获得新鲜的胃癌临床组织,经Pronase蛋白酶酶解、乙醇醇沉等方法处理获得糖胺聚糖链,利用多种硫酸软骨素裂解酶获得CS二糖,进一步通过LC-MRM-MS/MS对临床组织中CS表达谱进行定量分析,从而深入阐释不同种类CS二糖的临床意义。结果 临床胃癌组织中共检测到8种类型CS二糖,其中CS-4S含量最高,其次是CS-6S、CS-2S、CS-2S4S、CS-4S6S、CS-TriS,未硫酸化的CS-0S含量最少；相关性分析结果显示,临床胃癌组织中CS-2S、CS-4S、CS-6S表达量高的患者出现淋巴转移的可能性更高；CS-4S、CS-6S表达量与胃癌患者TNM分期具有正相关性。结论 采用灵敏高效的LC-MRM-MS/MS技术阐明了临床胃癌组织中CS表达谱,并发现个别种类CS二糖在临床胃癌组织中的表达量与胃癌患者临床指征相关,其有望成为胃癌生物标志物应用于疾病诊断与精准化治疗。 |
| English Summary: |
| Objective In this study, Chondroitin sulfate（CS） disaccharides were extracted from gastric cancer clinical tissues, and sample pretreatment methods such as targeted enzymatic digestion and 2-AMAC fluorescent labelling were combined with mass spectrometry multiple reaction monitoring (MRM) technology. The aim was to investigate accurately, efficiently, and ultrasensitively quantify the expression profiles of CS in formalin-fixed, paraffin-embedded gastric cancer tissues and explore the correlation between the expression profiles of CS and various clinical indicators in patients with gastric cancer. Methods Fresh gastric cancer clinical tissues were obtained by dewaxing and hydration, processed by Pronase protease enzyme digestion and ethanol alcohol precipitation to obtain Glycosaminoglycan. Subsequently, it underwent treatment with chondroitin lyase to obtain CS disaccharides, and the expression profiles of CS in the clinical tissues were quantitatively determined using LC-MRM-MS/MS. The clinical significance of different types of CS disaccharides was then analysed. Results A total of eight types of CS disaccharides were detected in clinical gastric cancer tissues, among which CS-4S was found to be the highest, followed by CS-6S, CS-2S, CS-2S4S, CS-4S6S, CS-Tris, and unsulphated CS-0S was the least abundant; Correlation analysis revealed that the patients with elevated levels of CS-2S, CS-4S, and CS-6S in their clinical gastric cancer tissues were more likely to experience lymphatic metastasis; Additionally, the levels of CS-4S and CS-6S were positively correlated with the TNM stage of gastric cancer patients. Conclusion The application of the LC-MRM-MS/MS technique enabled to elucidate the composition and content of CS expression profiles in clinical gastric cancer tissues. This analysis revealed that the expression of individual CS disaccharides in clinical gastric cancer tissues was correlated with the clinical indicators of gastric cancer patients. It is anticipated that these findings could be utilized as a biomarkers of gastric cancer for the application of disease diagnosis and precision therapy. |
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