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Exploring gene-network complexity in cancer

Researchers have studied the changes in gene-network structure occurring during the onset and progression of nine different cancer types, in the hope of leading to new treatment targets for chemotherapy.

Cancer is a complex disease. This is due to its environmental and genetic components, which interact through a variety of epigenetic mechanisms. Cancer cells usually display a loss of regulatory control over a variety of cellular functions relative to their normal precursor cells.

Loss in regulatory control has historically been monitored by changes in gene expression. But recently it has been recognised that investigations into the regulatory changes that underlie cancer must also consider alterations in gene-gene network interactions. However, little is currently known about changes in gene-network structure associated with progression of cancer from early to late stages of development. 

Changes in cancer gene-network structure

Recently, a group of researchers studied the changes in gene-network structure occurring during the onset and progression of nine different cancer types. The results, published in iScience, revealed novel changes in cancer gene interactions that are hoped to lead to new treatment targets for chemotherapy.

The team employed an unsupervised approach of network construction and found that cancer was generally associated with an overall reduction in network complexity, with 96.73% of gene-gene connections present in normal tissues being lost in their corresponding cancer tissues. However, they also found that many new gene-gene connections were acquired in cancer, accounting for around 69.05% of network connections present in these transformed cells. Moreover, when examining cross-tissue network similarity between precursor normal tissues and their respective cancers, the researchers noted a 9.7% increase in shared network genes across the nine types of cancer in the study.

Zainab Arshad, co-author of the paper, summarised:

“What I think is most remarkable about our findings is that the vast majority of changes -more than 90% – in the network of interactions accompanying cancer are not associated with genes displaying changes in their expression. What this means is that genes playing a central role in bringing about changes in network structure associated with cancer – the ‘hub genes’ – may be important new targets for gene therapy that can go undetected by gene expression analyses.”

The role of gene-networks in cancer research

Overall, the findings from this study indicate that changes in gene-network interactions play a significant role in cancer onset and progression. This suggests that such system-level approaches to cancer may not only expand our understanding of the underlying molecular basis of the disease, but also enhance our ability to identify important new candidates for targeted gene therapy.

John McDonald, co-author of the paper, explained:

“We observe re-establishment of high levels of network complexity, but the genes comprising the complex networks associated with advanced cancers are quite different from those comprising the complex networks associated with the precursor normal tissues. As cancers evolve in function, they are typically associated with changes in DNA structure, and/or with changes in the RNA expression of cancer driver genes. Our results indicate that there’s an important third class of changes going on – changes in gene interactions – and many of these changes are not detectable if all you’re looking for are changes in gene expression.”

Image credit: Memorial Sloan Kettering Cancer Center

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Cancer / Cancer Research / Gene