Nicholas Ben, Bailey Alistair, McCann Katy J, Johnson Peter, Elliott Tim, Ottensmeier Christian, Skipp Paul
Centre for Proteomic Research, School of Biological Sciences and Institute for Life Sciences, University of Southampton, Building 85, Southampton SO17 1BJ ,U.K.
Centre for Cancer Immunology and Institute for Life Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD ,U.K.
J Proteome Res. 2025 Feb 7;24(2):729-741. doi: 10.1021/acs.jproteome.4c00773. Epub 2025 Jan 8.
Non-small cell lung cancer (NSCLC) is frequently diagnosed late and has poor survival. The two predominant subtypes of NSCLC, adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), are currently differentially diagnosed using immunohistochemical markers; however, they are increasingly recognized as very different cancer types suggestive of potential for new, more targeted therapies. There are extensive efforts to find more precise and noninvasive differential diagnostic tools. Here, we examined these two NSCLC subtypes for differences that may inform treatment and identify potential novel therapeutic pathways. We presented a comparative analysis of transcriptomic and proteomic expression in tumors from a cohort of 22 NSCLC patients: 8 LUSC and 14 LUAD. Comparing NSCLC subtypes, we found differential gene expression related to cell differentiation for LUSC and cellular structure and immune response regulation for LUAD. Differential protein expression between NSCLC subtypes was related to extracellular structure for LUSC and metabolic processes, including glucose metabolism for LUAD. This direct comparison was more informative about subtype-specific pathways than between each subtype and control (nontumor) tissues. Many of our observations between NSCLC subtypes support and inform existing observations and reveal differences that may aid research seeking to identify and validate novel subtype biomarkers or druggable targets.
非小细胞肺癌（NSCLC）常常在晚期才被诊断出来，生存率较低。NSCLC的两种主要亚型，即腺癌（LUAD）和鳞状细胞癌（LUSC），目前使用免疫组化标志物进行鉴别诊断；然而，它们越来越被认为是截然不同的癌症类型，提示有开发新的、更具针对性治疗方法的潜力。人们正在广泛努力寻找更精确和非侵入性的鉴别诊断工具。在此，我们研究了这两种NSCLC亚型之间的差异，这些差异可能为治疗提供依据并确定潜在的新型治疗途径。我们对22例NSCLC患者（8例LUSC和14例LUAD）肿瘤的转录组和蛋白质组表达进行了比较分析。比较NSCLC亚型时，我们发现LUSC与细胞分化相关的基因表达存在差异，而LUAD与细胞结构和免疫反应调节相关。NSCLC亚型之间的蛋白质表达差异与LUSC的细胞外结构以及LUAD的代谢过程（包括葡萄糖代谢）有关。这种直接比较比每个亚型与对照（非肿瘤）组织之间的比较更能提供有关亚型特异性途径的信息。我们在NSCLC亚型之间的许多观察结果支持并补充了现有观察结果，揭示了可能有助于识别和验证新型亚型生物标志物或可药物靶向的差异。
