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- Title
Spatially Resolved Proteomic and Transcriptomic Profiling of Anaplastic Lymphoma Kinase-Rearranged Pulmonary Adenocarcinomas Reveals Key Players in Inter- and Intratumoral Heterogeneity.
- Authors
Szeitz, Beáta; Glasz, Tibor; Herold, Zoltán; Tóth, Gábor; Balbisi, Mirjam; Fillinger, János; Horváth, Szabolcs; Mohácsi, Réka; Kwon, Ho Jeong; Moldvay, Judit; Turiák, Lilla; Szász, Attila Marcell
- Abstract
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) and proteomic profiling to investigate seven treatment-naïve pADCs with an ALK 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 r = 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 FN1, 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.
- Subjects
PROTEOMICS; TRANSCRIPTOMES; HETEROGENEITY; ADENOCARCINOMA; PROTEIN expression; GENE expression profiling
- Publication
International Journal of Molecular Sciences, 2023, Vol 24, Issue 14, p11369
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms241411369