Riss J et al. (2006) Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma. Cancer Res 66: 7216–7224

It has been suggested that cancers are analogous to wounds that do not heal. To examine whether cancer and tissue regeneration share common molecular phenotypes, Riss et al. used a microarray approach to compare the gene expression profiles underlying human renal cell carcinoma (RCC) and renal regeneration and repair (RRR).

The researchers compared the gene expression profile of RRR from a mouse model of unilateral renal ischemia and reperfusion with that of a set of genes differentially expressed in RCC relative to normal kidney samples identified through a literature search. They identified 361 genes that were differentially expressed in both RRR and RCC. Of the differentially expressed genes, 77% were concordantly regulated, revealing a significant similarity between the two gene expression signatures (P=2.2×10−16) and supporting the concept of cancers as wounds that do not heal. The remaining 83 genes were discordantly expressed in RRR and RRC (i.e. upregulated genes in RCC were downregulated in RRR and vice versa). Pathway and gene ontology analysis of the concordant gene group revealed that normal RRR processes such as cell proliferation and growth, translation, immune response and metabolism also occur in RCC. By contrast, the discordant gene list was enriched in genes involved in morphogenesis, glycolysis, and the hypoxia-inducible factor and insulin-like growth factor 1 pathways, which might reflect RCC pathogenesis. Further analysis of the discordantly regulated genes might provide insight into the differences between normal tissue regeneration and malignancy and may help develop novel diagnostic and therapeutic targets specific to carcinoma.