Infiltration of B cell may underlie the contrary sex- and age-related biological behavior of papillary thyroid carcinoma

Abstract

Background and purpose Sex and age play complex and contrary roles in the pathogenesis, lymph node metastasis (LNM), and prognosis of papillary thyroid carcinoma (PTC). This study aimed to explore the underlying mechanism of this phenomenon.Method The risk factors for LNM were explored by combining local data and the Surveillance, Epidemiology, and End Results (SEER) database of PTC. The gene expression information of 497 samples from The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) was used to explore the differentially expressed genes (DEGs) among different phenotypes. The single-cell RNA sequencing (scRNA-seq) data obtained from the Gene Expression Omnibus (GEO) database was used to explore the aimed gene expression in specific cell types. The flow cytometry was used to explore peripheral lymphocyte subsets in PTC.Results The clinical data showed that the younger age and the male sex were the risk factors for LNM (P < 0.05). In the bulk gene analysis, the age- and sex-related DEGs in contrary trends between different tissues and LNM state were two intersection genes:TCL1A and CR2. The analysis of scRNA-seq from the GEO database showed that the genes TCL1A and CR2 were mainly expressed in B cells, and the infiltration of B cells varied among different tissues. The peripheral blood lymphocyte subsets showed that the composition of circulating lymphocytes was different in different lymph node metastasis states and age levels.Conclusion The infiltration of TCL1A and CR2 related B cells for different ages and sexes might explain the contradictory biological behavior, including tumor pathogenesis, LNM, and prognosis of PTC.