Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay.
Novel circulating peptide biomarkers for esophageal squamous cell carcinoma revealed by a magnetic bead-based MALDI-TOFMS assay.
复制标题
基于磁珠的 MALDI-TOFMS 检测揭示了食管鳞状细胞癌的新型循环肽生物标志物
DOI：
10.18632/oncotarget.8123
复制
发表时间：
2016-04-26
期刊：
影响因子：
--
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Jia K;Li W;Wang F;Qu H;Qiao Y;Zhou L;Sun Y;Ma Q;Zhao X
食管鳞状细胞癌是世界上最常见的恶性肿瘤之一。由于缺乏明显的早期症状，患者往往在晚期被诊断，预后不良。在这里，我们应用高通量血清肽组分析，以确定循环肽标志物的ESCC。弱阳离子交换磁珠耦合基质辅助激光解吸/电离飞行时间质谱用于两个阶段的蛋白质型肽分析复杂的血清样品收集477例癌症患者和健康对照。我们建立了一个包含1，925.5，2，950.6和5，900.0 Da的三个显著差异表达肽的遗传算法模型，其灵敏度和特异性分别为97.00%和95.92%，在训练集和验证集分别为97.03%和100.00%。该模型的诊断能力明显优于SCC-Ag和Cyfra 21-1，特别是对早期ESCC的诊断，达到96.94%的灵敏度。随后，这些肽被确定为AHSG，TSP 1和FGA片段的线性离子阱轨道阱混合串联质谱。值得注意的是，证实了ESCC中TSP 1的组织和血清水平增加，并与疾病进展相关。此外，组织TSP 1是ESCC的独立预后不良因素。总之，新建立的循环肽组和鉴定的蛋白质可以作为早期检测和诊断ESCC的潜在生物标志物。然而，需要更大的队列来进一步明确验证其临床应用。
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant neoplasms worldwide. Patients are often diagnosed at advanced stages with poor prognosis due to the absence of obvious early symptoms. Here, we applied a high-throughput serum peptidome analysis to identify circulating peptide markers of ESCC. Weak cationic exchange magnetic beads coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used for two-stage proteotypic peptide profiling in complex serum samples collected from 477 cancer patients and healthy controls. We established a genetic algorithm model containing three significantly differentially expressed peptides at 1,925.5, 2,950.6 and 5,900.0 Da with a sensitivity and specificity of 97.00% and 95.92% in the training set and 97.03% and 100.00% in the validation set, respectively. The model's diagnostic capability was significantly better than SCC-Ag and Cyfra 21–1, especially for early stage ESCC, with an achieved sensitivity of 96.94%. Subsequently, these peptides were identified as fragments of AHSG, TSP1 and FGA by linear ion trap-orbitrap hybrid tandem mass spectrometry. Notably, increased tissue and serum levels of TSP1 in ESCC were verified and correlated with disease progression. In addition, tissue TSP1 was an independent poor prognostic factor in ESCC. In conclusion, the newly established circulating peptide panel and identified proteins could serve as potential biomarkers for the early detection and diagnosis of ESCC. Nevertheless, a larger cohort will be required for further unequivocal validation of their clinical application.
登录
查看更多内容
影响因子：
2.8
作者：
Fan, Nai-Jun;Gao, Chun-Fang;Qiao, Liang
通讯作者：
Qiao, Liang
影响因子：
15.9
作者：
Bornstein, P
通讯作者：
Bornstein, P
影响因子：
4.4
作者：
Shi, Qian;Harris, Lyndsay N.;Miron, Alexander
通讯作者：
Miron, Alexander
影响因子：
2.9
作者：
Padoan, Andrea;Seraglia, Roberta;Plebani, Mario
通讯作者：
Plebani, Mario
DOI：
10.1158/1078-0432.ccr-15-0879
发表时间：
2016-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jenkinson C;Elliott VL;Evans A;Oldfield L;Jenkins RE;O'Brien DP;Apostolidou S;Gentry-Maharaj A;Fourkala EO;Jacobs IJ;Menon U;Cox T;Campbell F;Pereira SP;Tuveson DA;Park BK;Greenhalf W;Sutton R;Timms JF;Neoptolemos JP;Costello E
通讯作者：
Costello E