Abstract
BackgroundPapillary thyroid carcinoma (PTC) is the main pathological type of thyroid carcinoma (TC). Gender is a prominent background parameter for patients with PTC. Here, we aimed to delineate the differences in cell clusters and immune microenvironment in relation to gender in PTC.Methods We generated 6720, 14,666, and 33,373 single-cell transcriptomes that were pooled from the tissues of four male patients with PTC, seven female patients with PTC, and three patients with nodular goiter, respectively. We performed single-cell RNA-sequencing (scRNA-seq) based on BD Rhapsody and characterized the first single-cell transcriptomic landscape of PTC involving gender. The differential cell clusters and their gene profiles were identified and analyzed via a multi-resolution network in male and female patients. The interactions of fibroblasts and endothelial cells with malignant epithelial cells and the difference in the immune infiltration of B and T lymphocytes according to gender were assessed.ResultsMalignant epithelial cells were divided into two distinct subsets in male and female patients with PTC. Moreover, significant differences involving inferred copy-number variations (CNVs), gene profiles, and cell differentiation were detected between male and female patients. Regarding the interactions of fibroblasts and endothelial cells with malignant epithelial cells, members of the human leukocyte antigen (HLA) family and their receptors were considered as typical in female patients with PTC, while transforming growth factor beta 1 (TGFB1) and its receptors were typical of male patients with PTC. The characteristics of B cells, including cell clusters, cell differentiation, and dominant gene sets, were significantly different between genders.ConclusionsOur data revealed the detailed differences in cell clusters and immune microenvironment in PTC according to gender at the single-cell level, which provided new insights into the understanding of the impact of gender on PTC.
Highlights
Thyroid cancer is the most common endocrine-system malignancy worldwide [1, 2]
All cell clusters were differentiated according to the three disease statuses, which showed that the dominant clusters were different between male and female patients (Fig. 1b)
We focused on malignant epithelial cells, fibroblasts, endothelial cells, T cells and B cells by analyzing the differences in cell differentiation and gene expression profiles, as well as their interactions according to gender (Fig. 1d)
Summary
Thyroid cancer is the most common endocrine-system malignancy worldwide [1, 2]. PTC is the most common histopathological type of TC, accounting for about 75–85% [3]. The incidence of PTC in women is significantly higher than that in men and the female-to-male ratio is about three or more [1, 4]. Females exhibit a higher incidence of PTC, male gender has been shown to be associated with higher rates of advanced disease stage and a worse disease prognosis. Machens and colleagues performed a retrospective cohort analysis and the results showed that the primary tumor size of PTC in male patients was significantly larger than that in female patients and male patients had a higher incidence of lymph node metastases and distant metastases [8].
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