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

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Testis specific protein Y-encoded (TSPY) is a Y-chromosome proto-oncogene primarily found in male germ cells and germ cell tumors.
• Ectopic TSPY expression in somatic cancers, like liver cancer, suggests a role in oncogenesis beyond germ cells.
• The relationship between TSPY expression and other oncogenic events in TSPY-positive cancers is not well understood.

Purpose of the Study:

• To investigate the correlation between TSPY expression and other molecular features in clinical cancer samples.
• To identify genes co-expressed with TSPY and define a TSPY co-expression network (TCN).
• To analyze the methylation patterns of TCN genes in relation to their expression.

Main Methods:

• Utilized RNA-sequencing transcriptome and DNA methylation data from The Cancer Genome Atlas (TCGA) database.
• Identified 53 genes consistently co-expressed with TSPY, forming the TSPY co-expression network (TCN).
• Analyzed gene expression and DNA methylation levels in various cancer types.

Main Results:

• A TSPY co-expression network (TCN) comprising 53 genes, including LIN28B and RBMY, was identified.
• TCN genes were significantly co-activated in subsets of liver hepatocellular carcinoma (30%) and lung adenocarcinoma (10%).
• TCN-active cancers exhibited globally lower DNA methylation levels compared to TCN-silent cancers.

Conclusions:

• The TSPY co-expression network (TCN) is specifically activated in certain liver and lung cancers.
• Lower DNA methylation in TCN-active cancers suggests epigenetic regulation.
• TCN genes show potential as biomarkers for cancer diagnosis, prognosis, and management, particularly in liver and lung cancers.