Department of Biomedicine and Genetics, Medical University of Lodz, 92-213 Lodz, Poland.
Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, 90-924 Lodz, Poland.
Int J Mol Sci. 2023 Sep 5;24(18):13669. doi: 10.3390/ijms241813669.
A thorough study of the exosomal proteomic cargo may enable the identification of proteins that play an important role in cancer development. The aim of this study was to compare the protein profiles of the serum exosomes derived from non-small lung cancer (NSCLC) patients and healthy volunteers (control) using the high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS) method to identify potentially new diagnostic and/or prognostic protein biomarkers. Proteins exclusively identified in NSCLC and control groups were analyzed using several bioinformatic tools and platforms (FunRich, Vesiclepedia, STRING, and TIMER2.0) to find key protein hubs involved in NSCLC progression and the acquisition of metastatic potential. This analysis revealed 150 NSCLC proteins, which are significantly involved in osmoregulation, cell-cell adhesion, cell motility, and differentiation. Among them, 3 proteins: Interleukin-34 (IL-34), HLA class II histocompatibility antigen, DM alpha chain (HLA-DMA), and HLA class II histocompatibility antigen, DO beta chain (HLA-DOB) were shown to be significantly involved in the cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) infiltration processes. Additionally, detected proteins were analyzed according to the presence of lymph node metastasis, showing that differences in frequency of detection of protein FAM166B, killer cell immunoglobulin-like receptor 2DL1, and olfactory receptor 52R1 correlate with the N feature according to the TNM Classification of Malignant Tumors. These results prove their involvement in NSCLC lymph node spread and metastasis. However, this study requires further investigation.
对细胞外囊泡蛋白质组进行深入研究，可以识别出在癌症发展中起重要作用的蛋白质。本研究旨在采用高效液相色谱-质谱联用（HPLC-MS）方法比较非小细胞肺癌（NSCLC）患者和健康志愿者（对照）血清外泌体的蛋白质谱，以鉴定潜在的新的诊断和/或预后蛋白生物标志物。使用多种生物信息学工具和平台（FunRich、Vesiclepedia、STRING 和 TIMER2.0）对仅在 NSCLC 和对照组中鉴定到的蛋白质进行分析，以寻找参与 NSCLC 进展和获得转移潜能的关键蛋白枢纽。该分析揭示了 150 种 NSCLC 蛋白，这些蛋白显著参与渗透调节、细胞-细胞黏附、细胞迁移和分化。其中，3 种蛋白：白细胞介素 34（IL-34）、HLA Ⅱ类组织相容性抗原，DM alpha 链（HLA-DMA）和 HLA Ⅱ类组织相容性抗原，DO beta 链（HLA-DOB）被证明与癌症相关成纤维细胞（CAFs）和肿瘤相关巨噬细胞（TAMs）浸润过程显著相关。此外，还根据是否存在淋巴结转移对检测到的蛋白质进行了分析，结果表明蛋白 FAM166B、杀伤细胞免疫球蛋白样受体 2DL1 和嗅觉受体 52R1 的检测频率差异与 TNM 恶性肿瘤分类中的 N 特征相关。这些结果证明了它们在 NSCLC 淋巴结扩散和转移中的参与。然而，这项研究需要进一步的调查。
