Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer

IF 1.6 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Proteome Science Pub Date : 2021-12-03 DOI:10.21203/rs.3.rs-1084524/v1

Lingling Li, Hui Liu, Yan Li, Chun-feng Guo, Bing Wang, D. Shen, Qiao‐an Zhang, Chen Ding

{"title":"Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer","authors":"Lingling Li, Hui Liu, Yan Li, Chun-feng Guo, Bing Wang, D. Shen, Qiao‐an Zhang, Chen Ding","doi":"10.21203/rs.3.rs-1084524/v1","DOIUrl":null,"url":null,"abstract":"Background The surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer. Methods In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC). Results We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic. Conclusion We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic. Graphical Abstract","PeriodicalId":20857,"journal":{"name":"Proteome Science","volume":"20 1","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2021-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proteome Science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.21203/rs.3.rs-1084524/v1","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}

引用次数: 1

Abstract

Background The surveillance and therapy of early-stage cancer would be better for patients’ prognosis. However, the extreme trace amount of tissue samples in different stages have limited in portraying the characterization of early-stage cancer. Therefore, we focused on and presented comprehensive proteomic and phosphoproproteomic profiling of the trace FFPE samples from early-stage gastrointestinal cancer, and then explored the potential biomarkers of early-stage gastrointestinal cancer. Methods In this study, a quantitative proteomic method with chromatography with mass spectrometry (LC-MS/MS) was used to analyse the proteomic difference between the trace early-stage esophageal squamous cell carcinoma (EESCC) and early-stage duodenum adenocarcinoma cancer (EDAC). Results We identified ~ 6000 proteins and > 10,000 phosphosites in single trace FFPE samples. Comparative analysis disclosed the diverse proteomic features of tumor tissues compared with paired normal tissue of EESCC and EDAC, and revealed the difference of EESCC and EDAC was derived from their origin normal tissue. The distinct separation of EESCC and EDAC illustrated the functions of cell cycle (RB1 T373, EGFR T693) in EESCC, and the positive impacts of apoptosis, metabolic processes (MTOR and MTOR S1261) in EDAC. Furthermore, we deconvoluted the immune infiltration of early-stage gastrointestinal cancer, in which higher immune cell signatures were detected in EDAC, and showed the specific cytokines in EESCC and EDAC. We performed kinases-substates relationship analysis and elucidated the specific proteomic kinase characterization of EESCC and EDAC, and proposed the medicative effects and corresponding drugs for EESCC and EDAC at the clinic. Conclusion We disclosed the specific immune characterization of the early-stage gastrointestinal cancer, and presented potential makers of EESCC (EGFR, PDGFRB, CDK4, WEE1) and EDAC (MTOR, MAP2K1, MAPK3). This study represents a major stepping stone towards investigating the carcinogenesis mechanism of gastrointestinal cancer, and providing a rich resource for medicative strategy in the clinic. Graphical Abstract

查看原文本刊更多论文

早期胃肠道肿瘤中微量FFPE样品的综合蛋白质组学特征

背景早期肿瘤的监测和治疗有利于患者预后。然而，不同阶段的极微量组织样本在描绘早期癌症的特征方面受到限制。因此，我们关注并提出了早期胃肠道癌微量FFPE样本的综合蛋白质组学和磷酸化原蛋白质组学分析，进而探索早期胃肠道癌的潜在生物标志物。方法采用色谱-质谱联用定量蛋白质组学方法(LC-MS/MS)分析微量早期食管鳞状细胞癌(EESCC)和早期十二指肠腺癌(EDAC)的蛋白质组学差异。结果在单痕量FFPE样品中鉴定出约6000个蛋白和约10000个磷酸基。对比分析揭示了EESCC和EDAC的肿瘤组织与配对正常组织的不同蛋白质组学特征，并揭示了EESCC和EDAC的差异来源于其原正常组织。EESCC和EDAC的明显分离说明了细胞周期(RB1 T373、EGFR T693)在EESCC中的作用，以及EDAC中凋亡、代谢过程(MTOR和MTOR S1261)的积极影响。此外，我们对早期胃肠道肿瘤的免疫浸润进行了反卷积，发现在EDAC中检测到更高的免疫细胞特征，并显示了EESCC和EDAC中的特异性细胞因子。我们进行了激酶-底物关系分析，明确了EESCC和EDAC的特异性蛋白组激酶特征，并提出了EESCC和EDAC的临床疗效及相应药物。我们揭示了早期胃肠道肿瘤的特异性免疫特征，并提出了EESCC (EGFR、PDGFRB、CDK4、WEE1)和EDAC (MTOR、MAP2K1、MAPK3)的潜在致癌物。本研究为探索胃肠道肿瘤的癌变机制提供了重要的基础，并为临床用药策略提供了丰富的资源。图形抽象

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Proteome Science 生物-生化研究方法

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

4.5 months

期刊介绍： Proteome Science is an open access journal publishing research in the area of systems studies. Proteome Science considers manuscripts based on all aspects of functional and structural proteomics, genomics, metabolomics, systems analysis and metabiome analysis. It encourages the submissions of studies that use large-scale or systems analysis of biomolecules in a cellular, organismal and/or environmental context. Studies that describe novel biological or clinical insights as well as methods-focused studies that describe novel methods for the large-scale study of any and all biomolecules in cells and tissues, such as mass spectrometry, protein and nucleic acid microarrays, genomics, next-generation sequencing and computational algorithms and methods are all within the scope of Proteome Science, as are electron topography, structural methods, proteogenomics, chemical proteomics, stem cell proteomics, organelle proteomics, plant and microbial proteomics. In spite of its name, Proteome Science considers all aspects of large-scale and systems studies because ultimately any mechanism that results in genomic and metabolomic changes will affect or be affected by the proteome. To reflect this intrinsic relationship of biological systems, Proteome Science will consider all such articles.