Department of Biochemistry, Nanchong Key Laboratory of Metabolic Drugs and Biological Products, School of Preclinical Medicine, North Sichuan Medical, College, Nanchong, 637100, P. R. China.
Department of Chemistry, School of Preclinical Medicine, North Sichuan Medical College, Nanchong, 637100, P. R. China.
Proteomics Clin Appl. 2019 Jul;13(4):e1800038. doi: 10.1002/prca.201800038. Epub 2019 Jan 4.
To screen the novel biomarkers for gastric cancer and to determine the values of glutaminase 1 (GLS1) and gamma-glutamylcyclotransferase (GGCT) for detecting gastric cancer.
A discovery group of four paired gastric cancer tissue samples are labeled with Isobaric tag for relative and absolute quantitation agents and identified with LC-ESI-MS/MS. A validation group of 168 gastric cancer samples and 30 healthy controls are used to validate the expression of GLS1 and GGCT.
Four hundred and thirty-one proteins are found differentially expressed in gastric cancer tissues. Of these proteins, GLS1 and GGCT are found overexpressed in gastric cancer patients, with sensitivity of 75.6% (95% CI: 69-82.2%) and specificity of 81% (95% CI: 75-87%) for GLS1, and with sensitivity of 63.1% (95% CI: 55.7-71.5%) and specificity of 60.7% (95% CI: 53.3-68.2%) for GGCT. The co-expression of GLS1 and GGCT in gastric cancer tissues has sensitivity of 78.1% (95% CI: 70.1-86.1%) and specificity of 86.5% (95% CI: 79.5-93.4%). Moreover, both GLS1 and GGCT present higher expression of 82.6% (95% CI: 68.5-99.4%) and 73.9% (95% CI: 54.5-93.3%) in lymph node metastasis specimen than those in non-lymph node metastasis specimen. The areas under ROC curves are up to 0.734 for the co-expression of GLS1 and GGCT in gastric cancer. The co-expression of GLS1 and GGCT is strongly associated with histological grade, lymph node metastasis, and TNM stage Ⅲ/Ⅳ.
The present study provides the quantitative proteomic analysis of gastric cancer tissues to identify prognostic biomarkers of gastric cancer. The co-expression level of GLS1 and GGCT is of great clinical value to serve as diagnostic and therapeutic biomarkers for early gastric cancer.
筛选胃癌的新型生物标志物，并确定谷氨酰胺酶 1 (GLS1)和γ-谷氨酰环转移酶 (GGCT)在胃癌检测中的价值。
使用同位素质谱标签相对和绝对定量试剂对 4 对配对胃癌组织样本进行标记，并通过 LC-ESI-MS/MS 进行鉴定。使用 168 例胃癌样本和 30 例健康对照对 GLS1 和 GGCT 的表达进行验证。
在胃癌组织中发现了 431 种差异表达的蛋白质。在这些蛋白质中，GLS1 和 GGCT 在胃癌患者中过度表达，其灵敏度分别为 75.6%（95%CI：69-82.2%）和 81%（95%CI：75-87%），特异性分别为 63.1%（95%CI：55.7-71.5%）和 60.7%（95%CI：53.3-68.2%）。胃癌组织中 GLS1 和 GGCT 的共表达灵敏度为 78.1%（95%CI：70.1-86.1%），特异性为 86.5%（95%CI：79.5-93.4%）。此外，GLS1 和 GGCT 在淋巴结转移标本中的表达均高于非淋巴结转移标本，分别为 82.6%（95%CI：68.5-99.4%）和 73.9%（95%CI：54.5-93.3%）。GLS1 和 GGCT 共表达的 ROC 曲线下面积最高可达 0.734。GLS1 和 GGCT 的共表达与组织学分级、淋巴结转移和 TNM 分期Ⅲ/Ⅳ密切相关。
本研究提供了胃癌组织的定量蛋白质组学分析，以确定胃癌的预后生物标志物。GLS1 和 GGCT 的共表达水平具有重要的临床价值，可作为早期胃癌的诊断和治疗生物标志物。
