Comparative analysis of transcriptomic and proteomic expression between two non-small cell lung cancer subtypes

Ben Nicholas, Alistair Bailey, Katy J McCann, Peter Johnson, Tim Elliott, Christian Ottensmeier, Paul Skipp
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Abstract

Non-small cell lung cancer (NSCLC) is frequently diagnosed at an advanced stage and has poor survival. NSCLC subtypes require different treatment regimes, hence there are extensive efforts to find more precise and non-invasive differential diagnostics tools. Complementing these efforts, we examined two NSCLC subtypes for differences that may inform treatment options and identify potential novel therapeutic pathways. Here we present a comparative analysis of transcriptomic and proteomic expression in tumours from a cohort of 22 NSCLC patients: 8 squamous cell carcinoma (LUSC), 14 adenocarcinoma (LUAD). We examined differential gene and differential protein expression between LUSC and LUAD, and between NSCLC subtypes and either PBMCs or normal adjacent lung tissue (NAT). We found that both NSCLC subtypes shared common differences in gene expression to PBMC relating to developmental and structural changes, and common protein expression differences to NAT relating to protein translation and RNA related processing and splicing. Between NSCLC subtypes we found differential gene expression relating to cell differentiation for LUSC and cellular structure and immune response regulation for LUAD. Differential protein expression between NSCLC subtypes related to extracellular structure for LUSC and metabolic processes, including glucose metabolism for LUAD. Many of our observations of differentially expressed genes and proteins between NSCLC subtypes support and inform existing observations, aiding both basic and clinical research seeking to identify subtype biomarkers or druggable targets.
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两种非小细胞肺癌亚型的转录组和蛋白质组表达对比分析
非小细胞肺癌(NSCLC)常常在晚期才被诊断出来,而且生存率很低。非小细胞肺癌亚型需要不同的治疗方案,因此人们一直在努力寻找更精确的非侵入性鉴别诊断工具。作为这些努力的补充,我们研究了两种 NSCLC 亚型的差异,这些差异可能为治疗方案提供依据,并确定潜在的新型治疗途径。在此,我们对 22 例 NSCLC 患者肿瘤中的转录组和蛋白质组表达进行了比较分析:其中包括 8 例鳞状细胞癌(LUSC)和 14 例腺癌(LUAD)。我们研究了 LUSC 和 LUAD 之间以及 NSCLC 亚型与 PBMC 或正常邻近肺组织 (NAT) 之间的差异基因和差异蛋白表达。我们发现,这两种 NSCLC 亚型在基因表达上与 PBMC 存在共同差异,都与发育和结构变化有关;在蛋白质表达上与 NAT 存在共同差异,都与蛋白质翻译和 RNA 相关加工和剪接有关。在 NSCLC 亚型之间,我们发现 LUSC 的基因表达与细胞分化有关,而 LUAD 的基因表达与细胞结构和免疫反应调节有关。NSCLC亚型之间的蛋白质表达差异与LUSC的细胞外结构和LUAD的代谢过程(包括葡萄糖代谢)有关。我们对NSCLC亚型间差异表达基因和蛋白质的许多观察结果支持并充实了现有的观察结果,有助于基础和临床研究寻找亚型生物标志物或药物靶点。
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