Institute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Institute of Legal Medicine, University Hospital Münster, Münster, Germany.
Sci Rep. 2023 Nov 28;13(1):20948. doi: 10.1038/s41598-023-47767-5.
Lung cancer is the leading cause of cancer-related deaths worldwide with lung adenocarcinoma (LUAD) being the most common type. Genomic studies of LUAD have advanced our understanding of its tumor biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD are still insufficiently explored. The prognosis for lung cancer patients is still mostly determined by the stage of disease at the time of diagnosis. Focusing on late-stage metastatic LUAD with poor prognosis, we compared the proteomic profiles of primary tumors and matched distant metastases to identify relevant and potentially druggable differences. We performed high-performance liquid chromatography (HPLC) and electrospray ionization tandem mass spectrometry (ESI-MS/MS) on a total of 38 FFPE (formalin-fixed and paraffin-embedded) samples. Using differential expression analysis and unsupervised clustering we identified several proteins that were differentially regulated in metastases compared to matched primary tumors. Selected proteins (HK1, ATP5A, SRI and ARHGDIB) were subjected to validation by immunoblotting. Thereby, significant differential expression could be confirmed for HK1 and ATP5A, both upregulated in metastases compared to matched primary tumors. Our findings give a better understanding of tumor progression and metastatic spreads in LUAD but also demonstrate considerable inter-individual heterogeneity on the proteomic level.
肺癌是全球癌症相关死亡的主要原因，其中肺腺癌（LUAD）是最常见的类型。LUAD 的基因组研究提高了我们对其肿瘤生物学的认识，并加速了靶向治疗的发展。然而，LUAD 的蛋白质组特征仍未得到充分探索。肺癌患者的预后仍然主要取决于诊断时疾病的阶段。我们专注于预后不良的晚期转移性 LUAD，比较了原发肿瘤和匹配的远处转移的蛋白质组谱，以确定相关的和潜在的可用药差异。我们对总共 38 个 FFPE（福尔马林固定和石蜡包埋）样本进行了高效液相色谱（HPLC）和电喷雾串联质谱（ESI-MS/MS）分析。通过差异表达分析和无监督聚类，我们鉴定出了一些在转移灶中与匹配的原发灶相比差异调节的蛋白质。选择的蛋白质（HK1、ATP5A、SRI 和 ARHGDIB）通过免疫印迹进行验证。因此，与匹配的原发灶相比，HK1 和 ATP5A 的差异表达得到了显著证实，它们在转移灶中均上调。我们的研究结果更好地了解了 LUAD 中的肿瘤进展和转移扩散，但也证明了在蛋白质组水平上存在相当大的个体间异质性。
