Inter- and intratumoral proteomics and glycosaminoglycan characterization of ALK rearranged lung adenocarcinoma tissues: a pilot study

Abstract

Lung cancer is one of the most common types of cancer with limited therapeutic options, therefore a detailed understanding of the underlying molecular changes is of utmost importance. In this pilot study, we investigated the proteomic and glycosaminoglycan (GAG) profile of ALK rearranged lung tumor tissue regions based on the morphological classification, mucin and stromal content. Principal component analysis and hierarchical clustering revealed that both the proteomic and GAG-omic profiles are highly dependent on mucin content and to a lesser extent on morphology. We found that differentially expressed proteins between morphologically different tumor types are primarily involved in the regulation of protein synthesis, whereas those between adjacent normal and different tumor regions take part in several other biological processes (e.g. extracellular matrix organization, oxidation–reduction processes, protein folding) as well. The total amount and the sulfation profile of heparan sulfate and chondroitin sulfate showed small differences based on morphology and larger differences based on mucin content of the tumor, while an increase was observed in both the total amount and the average rate of sulfation in tumors compared to adjacent normal regions.

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

“…The GSEA analysis in our study confirmed that pROIs with higher mucin and stroma scores showed a prominent upregulation of ECM components, which again demonstrated the alignment between molecular-level findings and histologically visible ROI phenotypes. Contrasting our differential expression results with findings reported in Balbisi et al [19] and the CPTAC data revealed that the protein products of PRELP and BGN may be promising markers for increasing the mucin and stroma content in pADC tissues, respectively.…”

“…It is widely known that another tissue component, the stroma, affects tumor behavior as well [45]. Our previous publication on the hereby presented proteomic data also highlighted that proteomic and glycosaminoglycan profiles of individual tumor regions are highly dependent on mucin content and less on the stromal content [19]. The GSEA analysis in our study confirmed that pROIs with higher mucin and stroma scores showed a prominent upregulation of ECM components, which again demonstrated the alignment between molecular-level findings and histologically visible ROI phenotypes.…”

“…As demonstrated by a multitude of lung cancer studies [5][6][7][8], the integration of multiple omic datasets, such as genomics, transcriptomics or proteomics, can capture the complexity of the disease more effectively. Herein, we extended our previous proteomic results [19] with NanoString GeoMx gene expression profiling, enabling a spatial multi-omic characterization of ALK-driven pADCs prior to treatment with ALK inhibitors. First, we mapped protein and gene expression patterns and dysregulated pathways characteristic to tumor regions with distinct histopathological features.…”

“…Spatially resolved transcriptomic or proteomic studies of NSCLCs have been already utilized for biomarker discovery, in particular contributing to potential improvements in immunotherapy approaches [15][16][17][18]. Recently, we reported, for the first time, the proteomic and glycosaminoglycan characterization of seven pADCs with ALK rearrangement in a spatially resolved manner [19]. As demonstrated by a multitude of lung cancer studies [5][6][7][8], the integration of multiple omic datasets, such as genomics, transcriptomics or proteomics, can capture the complexity of the disease more effectively.…”

Interleukin-13 Treatment of Living Lung Tissue Model Alters the Metabolome and Proteome—A Nano-DESI MS Metabolomics and Shotgun Proteomics Study

“…These results suggest that the expression of mucins decreases in inflammatory asthma along with the rate of sialylation. The distribution of mucins has already been shown to substantially regulate the (glyco)proteomic profile of lung tissues in other diseases, such as lung cancer, as well [62]. Galectins, a protein family that binds to β-galactosides, were downregulated, while the Galectin-3-binding protein was non-significantly upregulated.…”