Identification of a TSPY co-expression network associated with DNA hypomethylation and tumor gene expression in somatic cancers

Testis specific protein Y-encoded (TSPY) is a Y-located proto-oncogene predominantly expressed in normal male germ cells and various types of germ cell tumor. Significantly, TSPY is frequently expressed in somatic cancers including liver cancer but not in adjacent normal tissues, suggesting that ectopic TSPY expression could be associated with oncogenesis in non-germ cell cancers. Various studies demonstrated that TSPY expression promotes growth and proliferation in cancer cells; however, its relationship to other oncogenic events in TSPY-positive cancers remains unknown. The present study seeks to correlate TSPY expression with other molecular features in clinical cancer samples, by analyses of RNA-seq transcriptome and DNA methylation data in the Cancer Genome Atlas (TCGA) database. A total of 53 genes, including oncogenic lineage protein 28 homolog B (LIN28B) gene and RNA-binding motif protein Y-linked (RBMY) gene, are identified to be consistently co-expressed with TSPY, and have been collectively designated as the TSPY co-expression network (TCN). TCN genes were simultaneously activated in subsets of liver hepatocellular carcinoma (30%) and lung adenocarcinoma (10%) regardless of pathological stage, but only minimally in other cancer types. Further analysis revealed that the DNA methylation level was globally lower in the TCN-active than TCN-silent cancers. The specific expression and methylation patterns of TCN genes suggest that they could be useful as biomarkers for the diagnosis, prognosis and clinical management of cancers, especially those for liver and lung cancers, associated with TSPY co-expression network genes.