Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, Japan.
Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.
Sci Rep. 2019 Jul 8;9(1):9816. doi: 10.1038/s41598-019-46404-4.
Tissue amino acid profiles depend on the cell types and extracellular components that constitute the tissue, and their functions and activities. We aimed to characterize the tissue amino acid profiles in several types of pancreatic tumors and lesions. We examined tissue amino acid profiles in 311 patients with pancreatic tumors or lesions. We used newly developed LC-MS/MS methods to obtain the profiles, which were compared with clinicopathological data. Each tumor or lesion presented a characteristic tissue amino acid profile. Certain amino acids were markedly altered during the multistep pancreatic carcinogenesis and pancreatic ductal adenocarcinoma (PDAC) progression. A tissue amino acid index (TAAI) was developed based on the amino acids that were notably changed during both carcinogenesis and cancer progression. Univariate and multivariate survival analyses revealed that PDAC patients with a high TAAI exhibited a significantly shorter survival rate, and these findings were validated using a second cohort. We suggest that tissue amino acid profiles are characteristic for normal tissue type, tumor histological type, and pathological lesion, and are representative of the cancer grade or progression stage in multistep carcinogenesis and of malignant characteristics. The TAAI could serve as an independent prognosticator for patients with PDAC.
组织氨基酸谱取决于构成组织的细胞类型和细胞外成分,以及它们的功能和活性。我们旨在描述几种胰腺肿瘤和病变的组织氨基酸谱。我们检查了 311 例胰腺肿瘤或病变患者的组织氨基酸谱。我们使用新开发的 LC-MS/MS 方法获得了这些谱,并将其与临床病理数据进行了比较。每个肿瘤或病变都呈现出独特的组织氨基酸谱。在多步骤胰腺发生和胰腺导管腺癌 (PDAC) 进展过程中,某些氨基酸明显改变。基于在癌变和癌症进展过程中明显改变的氨基酸,开发了组织氨基酸指数 (TAAI)。单因素和多因素生存分析显示,TAAI 较高的 PDAC 患者的生存率明显较低,这一发现使用第二个队列得到了验证。我们认为,组织氨基酸谱对于正常组织类型、肿瘤组织学类型和病理病变具有特征性,并且代表多步骤癌变中的癌症分级或进展阶段以及恶性特征。TAAI 可作为 PDAC 患者的独立预后指标。