Cancer-associated fibroblast marker signatures and stromal composition in usual interstitial pneumonia-associated lung adenocarcinoma: an analysis using a proteomic-immunohistochemical approach.
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引用次数: 0
Abstract
Lung adenocarcinoma (LUAD) associated with usual interstitial pneumonia (UIP) harbours distinct features compared to lung adenocarcinoma without UIP. Therefore, we aimed to characterise the tumour microenvironment of LUAD with UIP by focusing on cancer-associated fibroblasts (CAFs) and stromal composition. Immunohistochemistry was performed on 32 LUAD samples (16 each with and without UIP) to evaluate CAF marker expression and lymphocyte infiltration. Proteomic analysis of laser-microdissected stromal regions and reanalysis of publicly available single-cell RNA sequencing data were subsequently performed. LUAD with UIP had higher levels of podoplanin and collagen triple helix repeat containing 1 (CTHRC1) immunoreactivity, among the CAF markers examined in the fibrous stroma, increased inflammatory cell infiltration, and higher CD8 + and Foxp3 + lymphocyte counts than LUAD without UIP. The proteomic analysis revealed elevated aggrecan (ACAN) and hyaluronan and proteoglycan link protein 1 (HAPLN1) levels in the stroma of LUAD patients with UIP tissues, which was subsequently confirmed by immunohistochemistry. Single-cell RNA sequencing also supported ACAN and HAPLN1 expression in a subset of CAFs based on public data. The tumour microenvironment of LUAD in patients with UIP harbours distinct characteristics, including altered CAF markers and increased inflammatory cell infiltration in stromal components. Novel stromal proteins such as ACAN and HAPLN1 may play a role in the pathogenesis of LUAD with UIP.
期刊介绍：
Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.
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