Computational Mass Spectrometry & Proteomics Group, Carlos Chagas Institute, Fiocruz - Paraná, Brazil.
Laboratory of Proteomics, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Laboratory of Protein Chemistry, Proteomic Unit, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
J Proteomics. 2018 Jan 16;171:63-72. doi: 10.1016/j.jprot.2017.10.005. Epub 2017 Oct 12.
Gastric cancer is the fifth most common malignant neoplasia and the third leading cause of cancer death worldwide. Mac-Cormick et al. recently showed the importance of considering the anatomical region of the tumor in proteomic gastric cancer studies; more differences were found between distinct anatomical regions than when comparing healthy versus diseased tissue. Thus, failing to consider the anatomical region could lead to differential proteins that are not disease specific. With this as motivation, we compared the proteomic profiles of intestinal and diffuse adenocarcinoma from the same anatomical region, the corpus. To achieve this, we used isobaric labeling (iTRAQ) of peptides, a 10-step HILIC fractionation, and reversed-phase nano-chromatography coupled online with a Q-Exactive Plus mass spectrometer. We updated PatternLab to take advantage of the new Comet-PEFF search engine that enables identifying post-translational modifications and mutations included in neXtProt's PSI Extended FASTA Format (PEFF) metadata. Our pipeline then uses a text-mining tool that automatically extracts PubMed IDs from the proteomic result metadata and drills down keywords from manuscripts related with the biological processes at hand. Our results disclose important proteins such as apolipoprotein B-100, S100 and 14-3-3 proteins, among many others, highlighting the different pathways enriched by each cancer type.
Gastric cancer is a heterogeneous and multifactorial disease responsible for a significant number of deaths every year. Despite the constant improvement of surgical techniques and multimodal treatments, survival rates are low, mostly due to limited diagnostic techniques and late symptoms. Intestinal and diffuse types of gastric cancer have distinct clinical and pathological characteristics; yet little is known about the molecular mechanisms regulating these two types of gastric tumors. Here we compared the proteomic profile of diffuse and intestinal types of gastric cancer from the same anatomical location, the corpus, from four male patients. This methodological design aimed to eliminate proteomic variations resulting from comparison of tumors from distinct anatomical regions. Our PEFF-tailored proteomic pipeline significantly increased the identifications as when compared to previous versions of PatternLab.
胃癌是全球第五大常见恶性肿瘤，也是癌症死亡的第三大主要原因。Mac-Cormick 等人最近表明，在蛋白质组学胃癌研究中考虑肿瘤的解剖区域非常重要；与比较健康组织与患病组织相比，不同解剖区域之间的差异更大。因此，如果不考虑解剖区域，可能会导致不是疾病特异性的差异蛋白。基于此动机，我们比较了来自同一解剖区域胃体的肠型腺癌和弥漫型腺癌的蛋白质组图谱。为此，我们使用肽的等重同位素标记（iTRAQ）、10 步 HILIC 分级分离以及与 Q-Exactive Plus 质谱仪在线耦联的反相纳米色谱法。我们更新了 PatternLab，以利用新的 Comet-PEFF 搜索引擎，该引擎可识别包括在 neXtProt 的 PSI 扩展 FASTA 格式（PEFF）元数据中的翻译后修饰和突变。然后，我们的工作流程使用一个文本挖掘工具，该工具自动从蛋白质组学结果元数据中提取 PubMed ID，并从与手头生物过程相关的手稿中挖掘关键词。我们的结果揭示了一些重要的蛋白质，如载脂蛋白 B-100、S100 和 14-3-3 蛋白等，突出了每种癌症类型所富集的不同途径。
胃癌是一种异质性和多因素疾病，每年导致大量死亡。尽管手术技术和多模式治疗不断改进，但生存率仍然较低，这主要是由于诊断技术有限和症状出现较晚。肠型和弥漫型胃癌具有不同的临床和病理特征；然而，对于调节这两种类型胃癌肿瘤的分子机制知之甚少。在这里，我们比较了来自同一解剖位置胃体的弥漫型和肠型胃癌的蛋白质组图谱，来自四名男性患者。这种方法设计旨在消除由于比较来自不同解剖区域的肿瘤而导致的蛋白质组差异。与 PatternLab 的以前版本相比，我们专门针对 PEFF 的蛋白质组学工作流程大大增加了鉴定结果。
