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Context Although the incidence of papillary thyroid carcinoma (PTC) is significantly higher in females than in males, the prognosis of male PTC is more unfavorable. However, the cause of higher malignancy of PTC in male patients remains unclear. Objective We conducted our analysis on microarrays datasets, tissue samples from PTC patients and the RNAseq datasets from TCGA with survival data. Methods We searched all publicly available microarray datasets and performed a genome-wide meta-analysis comparing PTC and normal samples. Gene Ontology analysis was then conducted. The candidate genes were tested by quantitative real-time polymerase chain reaction. The analysis of prognostic value of genes was performed with datasets from The Cancer Genome Atlas. Results After meta-analyses, 150 significantly differentially expressed genes (DEGs) were specifically found in male subjects. Gene Ontology analysis of these 150 genes revealed that the viral process was activated. Seven genes involved in the viral process in male patients showed a significantly differential expression between PTC and normal tissue. Survival analysis exhibited that the 7 genes, used in combination, were prognostically valuable and, of them, PSMB1 possessed a conspicuous prognostic value, especially in males. Conclusion In this study, we searched all publicly available microarray datasets and conducted a comprehensive analysis to understand the male propensity for higher malignancy. We found that markers of viral infection showed significantly differential expression only in male patients compared with their female counterparts and had a sex-sensitive prognostic value in PTC.

A Set of Markers Related to Viral Infection Has a Sex-sensitive Prognostic Value in Papillary Thyroid Carcinoma