The Sex and Age-Associated Infiltration of B Cells May Result in the Dimorphic Behaviors Observed in Papillary Thyroid Carcinomas

Background and Purpose: Sex and age show a dimorphism role in the pathogenesis, lymph node metastasis, and prognostic outcomes of papillary thyroid carcinoma. This investigation endeavors to elucidate the mechanisms underlying these disparities. Methods: The clinicopathological characteristics and risk factors of lymph node metastasis were explored by analyzing the 2261 patients. The gene expression information of 497 samples from The Cancer Genome Atlas Thyroid Cancer database was used to explore the differentially expressed genes in different phenotypes. What’s more, the single-cell RNA sequencing data obtained from the Gene Expression Omnibus database was used to explore the gene expression in specific cells. Results: Multivariate logistic regression analysis showed that in male patients, a larger tumor size, extrathyroidal extension, younger age, and the presence of calcification emerged as significant predictors for lymph node metastasis (LNM)(p < 0.05). Conversely, female patients exhibited a different profile, with larger tumor size, extrathyroidal extension, younger age, calcification, and bilateral tumors being identified as key risk factors (p < 0.05). Further stratification by age demonstrated distinct patterns: among the younger cohort, a larger tumor size, extrathyroidal extension, male gender, calcification, multifocality, and the presence of Hashimoto’s thyroiditis held statistical significance (p < 0.05). In contrast, the older subgroup was characterized by a larger tumor size, extrathyroidal extension, male gender, calcification, bilateral tumors, and unclear margins as salient indicators of risk (p < 0.05). In the bulk gene analysis, there were two sex-age-related differentially expressed genes with a contrary trend in tissue sources and LNM status: TCL1A and CR2. The analysis of single-cell RNA sequencing showed that the infiltration of TCL1A - and CR2 -related B cells varied in different clinical subtypes. Conclusion: Lymph node metastasis of papillary thyroid carcinoma in different sexes and ages may have distinct patterns, and the ages-sex-related B cell infiltration might explain the dimorphism biological behavior. Keywords: papillary thyroid carcinoma, lymph nodes metastasis, sex, age, immune microenvironment