Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer.
Integrative proteomic characterization of trace FFPE samples in early-stage gastrointestinal cancer.
复制标题
早期胃肠道癌中痕量FFPE样本的综合蛋白质组学表征。
DOI：
10.1186/s12953-022-00188-0
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发表时间：
2022-04-09
期刊：
影响因子：
2
通讯作者：
Ding C
中科院分区：
文献类型：
--
作者：
Li L;Liu H;Li Y;Guo C;Wang B;Shen D;Zhang Q;Ding C
早期肿瘤的监测和治疗对患者的预后更有利。然而，不同阶段的组织样本的极微量限制了描绘早期癌症的特征。因此，我们集中并提出了全面的蛋白质组学和磷酸化蛋白质组学分析的痕量FFPE样品从早期胃肠道癌症，然后探索早期胃肠道癌症的潜在生物标志物。本研究采用色谱-质谱联用（LC-MS/MS）定量蛋白质组学方法，分析微量早期食管鳞状细胞癌（EESCC）和早期十二指肠腺癌（EDAC）的蛋白质组差异。我们在单一痕量FFPE样品中鉴定了约6000种蛋白质和> 10，000个磷酸化位点。比较分析显示，EESCC和EDAC肿瘤组织与配对正常组织蛋白质组学特征存在差异，且EESCC和EDAC的差异来源于其来源的正常组织。EESCC和EDAC的明显分离说明了细胞周期（RB 1 T373、EGFR T693）在EESCC中的作用，以及细胞凋亡、代谢过程（MTOR和MTOR S1261）在EDAC中的积极影响。此外，我们对早期胃肠道癌的免疫浸润进行了去卷积，其中在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。通过激酶-亚基关系分析，阐明EESCC和EDAC的特异性蛋白质组学激酶特征，并提出临床治疗EESCC和EDAC的疗效及相应药物。我们揭示了早期胃肠道肿瘤的特异性免疫学特征，并提出了EESCC（EGFR，PDGFRB，CDK 4，WEE 1）和EDAC（MTOR，MAP 2K 1，MAPK 3）的潜在标志物。本研究为探讨胃肠道肿瘤的发生机制提供了重要的基础，并为临床治疗提供了丰富的资源。在线版本包含补充材料，可通过10.1186/s12953-022-00188-0获得。
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. 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). 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. 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. The online version contains supplementary material available at 10.1186/s12953-022-00188-0.
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