Phylostratigraphic analysis of gene co-expression network reveals the evolution of functional modules for ovarian cancer.

Ovarian cancer (OV) is an extremely lethal disease. However, the evolutionary machineries of OV are still largely unknown. Here, we used a method that combines phylostratigraphy information with gene co-expression networks to extensively study the evolutionary compositions of OV. The present co-expression network construction yielded 18,549 nodes and 114,985 edges based on 307 OV expression samples obtained from the Genome Data Analysis Centers database. A total of 20 modules were identified as OV related clusters. The human genome sequences were divided into 19 phylostrata (PS), the majority (67.45%) of OV genes was already present in the eukaryotic ancestor. There were two strong peaks of the emergence of OV genes screened by hypergeometric test: the evolution of the multicellular metazoan organisms (PS5 and PS6, P value = 0.002) and the emergence of bony fish (PS11 and PS12, P value = 0.009). Hence, the origin of OV is far earlier than its emergence. The integrated analysis of the topology of OV modules and the phylogenetic data revealed an evolutionary pattern of OV in human, namely, OV modules have arisen step by step during the evolution of the respective lineages. New genes have evolved and become locked into a pathway, where more and more biological pathways are fixed into OV modules by recruiting new genes during human evolution.