Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity

Pulmonary adenocarcinomas (pADCs) with an ALK 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) proteomic profiling investigate seven treatment-naïve pADCs rearrangement. On each FFPE tumor slide, 12 smaller 2–6 larger histopathologically annotated regions were selected for analysis, respectively. The correlation between proteomics transcriptomics was modest (average Pearson’s r = 0.43 at the gene level). Intertumoral more pronounced than intratumoral heterogeneity, normal adjacent tissue exhibited distinct characteristics. We identified potential markers dysregulated pathways associated tumors, varying extent of immune infiltration, as well mucin stroma content. Notably, some appeared be specific ALK-driven subset pADCs. Our data showed that within elements extracellular matrix, including FN1, substantial variability. Additionally, mapped co-localization patterns microenvironment elements. This study represents first spatially resolved both protein expression levels. findings may contribute better understanding type prior treatment inhibitors.