Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China.
J Cancer Res Clin Oncol. 2023 Sep;149(11):9285-9300. doi: 10.1007/s00432-023-04851-7. Epub 2023 May 19.
Mucinous adenocarcinoma (MC) is a distinct pathological subtype of colon adenocarcinoma, which is associated with a worse prognosis compared with non-mucinous adenocarcinoma (AC). However, clear distinctions between MC and AC remain unknown. Extracellular vesicles (EVs) are a class of enclosed vesicles containing proteins, lipids, and nucleic acids that are secreted by cells into surrounding tissues or into serum. The EVs could facilitate tumorigenesis by regulating tumor cell proliferation, invasiveness, metastasis, angiogenesis, and evasion of immune surveillance.
Quantitative proteomics analysis was performed to determine the characterization and biological differences of serum-derived EVs in two subtypes of colon adenocarcinoma (MC and AC). Serum-derived EVs from patients with MC, AC, and healthy volunteers were included in this study. The role of PLA2G2A in cell migration and invasion were evaluate with transwell assay, and its prognostic predictive value was further assessed based on TCGA database.
Quantitative proteomics analysis revealed 846 differentially expressed proteins (DEPs) in EVs from MC patients compared with those from AC patients. Bioinformatics analysis revealed that the most prominent protein cluster included those involved in cell migration and the tumor microenvironment. Overexpression of PLA2G2A, one of the key EV proteins upregulated in patients with MC, in colon cancer cell line SW480 promoted the cell invasion and migration ability. In addition, the high level of PLA2G2A is associated with poor prognosis of colon cancer patients harboring BRAF mutations. Further, after EV stimulation, proteomic analysis of recipient SW480 cells showed that MC-derived EVs activated multiple cancer-related pathways, including the Wnt/β-Catenin signaling pathway, and might promote the malignancy of mucinous adenocarcinoma through these pathways.
The identification of differential protein profiles between MC and AC helps to elucidate the underlying molecular mechanisms of MC pathogenesis. The PLA2G2A in EVs is a potential prognostic predictive marker for those patients harboring with BRAF mutations.
黏液腺癌（MC）是结直肠腺癌的一种独特病理亚型，与非黏液腺癌（AC）相比，其预后更差。然而，MC 和 AC 之间的明确区别仍不清楚。细胞外囊泡（EVs）是一类包含蛋白质、脂质和核酸的封闭囊泡，由细胞分泌到周围组织或血清中。EVs 通过调节肿瘤细胞增殖、侵袭、转移、血管生成和逃避免疫监视，促进肿瘤发生。
采用定量蛋白质组学分析方法，确定两种结直肠腺癌（MC 和 AC）患者血清来源 EVs 的特征和生物学差异。本研究纳入了 MC、AC 患者和健康志愿者的血清来源 EVs。通过 Transwell 实验评估 PLA2G2A 在细胞迁移和侵袭中的作用，并进一步基于 TCGA 数据库评估其预后预测价值。
定量蛋白质组学分析显示，与 AC 患者相比，MC 患者的 EV 中存在 846 个差异表达蛋白（DEPs）。生物信息学分析显示，最显著的蛋白簇包括与细胞迁移和肿瘤微环境相关的蛋白。在结肠癌细胞系 SW480 中过表达 PLA2G2A，这是 MC 患者上调的关键 EV 蛋白之一，可促进细胞侵袭和迁移能力。此外，PLA2G2A 水平高与携带 BRAF 突变的结直肠癌患者预后不良相关。进一步研究显示，经 EV 刺激后，SW480 细胞的蛋白质组学分析显示，MC 来源的 EV 激活了多个与癌症相关的通路，包括 Wnt/β-catenin 信号通路，并可能通过这些通路促进黏液性腺癌的恶性程度。
MC 和 AC 之间差异蛋白谱的鉴定有助于阐明 MC 发病机制的潜在分子机制。EVs 中的 PLA2G2A 是携带 BRAF 突变患者的潜在预后预测标志物。
