Division of Oncology, Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary.
Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, Hungary.
Int J Mol Sci. 2023 Jul 12;24(14):11369. doi: 10.3390/ijms241411369.
Pulmonary adenocarcinomas (pADCs) with an rearrangement are a rare cancer subtype, necessitating comprehensive molecular investigations to unravel their heterogeneity and improve therapeutic strategies. In this pilot study, we employed spatial transcriptomic (NanoString GeoMx) and proteomic profiling to investigate seven treatment-naïve pADCs with an rearrangement. On each FFPE tumor slide, 12 smaller and 2-6 larger histopathologically annotated regions were selected for transcriptomic and proteomic analysis, respectively. The correlation between proteomics and transcriptomics was modest (average Pearson's = 0.43 at the gene level). Intertumoral heterogeneity was more pronounced than intratumoral heterogeneity, and normal adjacent tissue exhibited distinct molecular characteristics. We identified potential markers and dysregulated pathways associated with tumors, with a varying extent of immune infiltration, as well as with mucin and stroma content. Notably, some markers appeared to be specific to the ALK-driven subset of pADCs. Our data showed that within tumors, elements of the extracellular matrix, including , exhibited substantial variability. Additionally, we mapped the co-localization patterns of tumor microenvironment elements. This study represents the first spatially resolved profiling of ALK-driven pADCs at both the gene and protein expression levels. Our findings may contribute to a better understanding of this cancer type prior to treatment with ALK inhibitors.
肺腺癌（pADCs）伴有重排是一种罕见的癌症亚型，需要进行全面的分子研究，以揭示其异质性并改善治疗策略。在这项初步研究中，我们采用空间转录组学（NanoString GeoMx）和蛋白质组学分析方法，对 7 例未经治疗的伴有重排的 pADCs 进行了研究。在每个 FFPE 肿瘤切片上，分别选择 12 个较小的和 2-6 个较大的组织病理学标记区域进行转录组和蛋白质组学分析。蛋白质组学和转录组学之间的相关性适中（基因水平上的平均 Pearson 相关系数为 0.43）。肿瘤间异质性比肿瘤内异质性更为明显，而正常相邻组织表现出明显的分子特征。我们鉴定了与肿瘤相关的潜在标志物和失调通路，这些通路具有不同程度的免疫浸润，以及粘蛋白和基质含量。值得注意的是，一些标志物似乎是 ALK 驱动的 pADCs 亚群所特有的。我们的数据表明，在肿瘤内，细胞外基质的成分，包括，表现出显著的变异性。此外，我们还绘制了肿瘤微环境成分的共定位模式。这项研究代表了首次在基因和蛋白质表达水平上对 ALK 驱动的 pADCs 进行空间分辨率的分析。我们的研究结果可能有助于在使用 ALK 抑制剂治疗之前，更好地了解这种癌症类型。
