Cell diversity and immune infiltration in the parathyroid tumour microenvironment

Abstract

Tumour microenvironment has been recognized as a crucial factor influencing disease progression. However, relevant features and function are insufficiently understood in parathyroid neoplasia. Single-cell RNA sequencing was performed to profile the transcriptome of 27,251 cells from four parathyroid adenoma (PA) tissue samples. External transcriptomic datasets and immunofluorescence staining of a tissue microarray was set for expression validation. Eight major cell types and various subpopulations were finely identified in PA. We found that a subcluster of tumour endocrine cells with low copy number variation probably presented as a resting state. Diverse infiltrating immune cell subtypes were identified, constructing an immunosuppressive microenvironment. Tumour-associated macrophages, which indicated an anti-inflammatory phenotype, significantly increased in PA. Inflammatory tumour-associated fibroblasts (iTAFs) was newly verified and highlighted on the role of stromal-immune crosstalk. Positive correlation between iTAFs and increased CD163+ macrophages was uncovered. Moreover, CXCL12 and receptors signalling was important for tumour angiogenesis and immune infiltration. Our findings provide a comprehensive landscape interpreting tumour cell heterogeneity, cell diversity, and immune regulation in parathyroid neoplasia. The valuable resources may promote the understanding of parathyroid tumour microenvironment.

Single‐Cell Transcriptomic Atlas of Parathyroid Adenoma and Parathyroid Carcinoma

“…There is a scarcity of data on PC because of a lack of sufficient amount and preservation of tissue. We performed high-precision scRNA-seq analyses on PC for the first time and compared them with PA, as there have only been two scRNA-seq studies performed on PA samples thus far (28,29) (Table 1). We identified the 11 major cell types described above in parathyroid tumors and revealed significant heterogeneity between parathyroid adenoma and carcinoma.…”

Fibroblast-based FN1CFD contributes to parathyroid cancer identification using integrated analysis

“…However, CAF is a heterogenous cell population with high plasticity and transformed to a speci c phenotype under distinct TME conditions. Consistent with CAF identi ed in thyroid cancer, colorectal cancer, liver cancer, etc., CAF in parathyroid tumors can be divided into mCAF and iCAF [21,36]. mCAF was characterized by high expression of POSTN, COL1A1, DCN and functioned as extracellular media to promote cancer cell invasion and metastasis.…”

High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesis

“…Some bulk transcriptomic and proteomic studies have suggested expression signatures of parathyroid chief and oxyphil cells, 5 , 6 , 7 but these studies were based on chief and oxyphil adenoma samples using whole tissue lysates. More recently, a single-cell RNA sequencing (scRNA-seq) study provided an expression atlas of the cell heterogeneity and tumour environment of parathyroid adenomas, 8 but there is still no data available on the normal parathyroid gland.…”