Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Graduate Institute of Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan.
Cancer Med. 2018 Jan;7(1):64-74. doi: 10.1002/cam4.1254. Epub 2017 Nov 17.
The use of blood plasma biomarkers in gastric cancer (GC) management is limited due to a lack of reliable biomarkers. An LC-MS/MS assay and a bioinformatic analysis were performed to identify blood plasma biomarkers in a GC discovery cohort. The data obtained were verified and validated by western blotting and an ELISA in an independent study cohort. A label-free quantification analysis of the MS data using PEAKS7 software found that four plasma proteins of apolipoprotein C-1, gelsolin, sex hormone-binding globulin (SHBG), and complement component C4-A were significantly overexpressed in GC patients. A western blot assay of these plasma proteins showed that only SHBG was consistently overexpressed in the patient group. ELISA measurement of SHBG blood plasma levels confirmed that the patient group had significantly higher SHBG levels than the control group. SHBG levels in the patient group remained significantly higher after being stratified by gender, age, and disease stage. These findings show that LC-MS/MS is powerful and highly sensitive for plasma biomarker discovery, and SHBG could be a potential plasma biomarker for GC management.
由于缺乏可靠的生物标志物,血浆生物标志物在胃癌 (GC) 管理中的应用受到限制。本研究采用 LC-MS/MS 分析和生物信息学分析,在 GC 发现队列中鉴定血浆生物标志物。通过 Western blot 和 ELISA 在独立研究队列中对获得的数据进行验证和验证。使用 PEAKS7 软件对 MS 数据进行无标记定量分析发现,载脂蛋白 C-1、凝胶蛋白、性激素结合球蛋白 (SHBG) 和补体成分 C4-A 这四种血浆蛋白在 GC 患者中明显过表达。这些血浆蛋白的 Western blot 检测显示,只有 SHBG 在患者组中持续过表达。ELISA 测量 SHBG 血浆水平证实,患者组的 SHBG 水平明显高于对照组。对性别、年龄和疾病阶段进行分层后,患者组的 SHBG 水平仍然明显较高。这些发现表明 LC-MS/MS 是一种强大且高度敏感的血浆生物标志物发现方法,SHBG 可能是 GC 管理的潜在血浆生物标志物。