Abstract
Network science is an emerging tool in systems biology and oncology, providing novel, system-level insight into the development of cancer. The aim of this project was to study the signaling networks in the process of oncogenesis to explore the adaptive mechanisms taking part in the cancerous transformation of healthy cells. For this purpose, colon cancer proved to be an excellent candidate as the preliminary phase, and adenoma has a long evolution time. In our work, transcriptomic data have been collected from normal colon, colon adenoma, and colon cancer samples to calculating link (i.e., network edge) weights as approximative proxies for protein abundances, and link weights were included in the Human Cancer Signaling Network. Here we show that the adenoma phase clearly differs from the normal and cancer states in terms of a more scattered link weight distribution and enlarged network diameter. Modular analysis shows the rearrangement of the apoptosis- and the cell-cycle-related modules, whose pathway enrichment analysis supports the relevance of targeted therapy. Our work enriches the system-wide assessment of cancer development, showing specific changes for the adenoma state.
Highlights
Colon cancer is a malignant tumor originating in the large intestine, which is histologically considered to be an adenocarcinoma in 95% of the cases
The authors considered the normal network to be a model network of a normal, healthy colon, the adenoma network to be that of a colon adenoma, and the carcinoma network to be that of a model network of colon adenocarcinoma
Modular reorganization and the analysis of the strongest and weakest links support the emergence of cancer hallmarks of constant proliferation and evading apoptosis in the carcinoma network since the cell cycle comes into prominence and the apoptotic modules unite
Summary
Colon cancer is a malignant tumor originating in the large intestine, which is histologically considered to be an adenocarcinoma in 95% of the cases. The relevance of this disease is hard to underestimate, as colorectal cancer (CRC) is the third most common cancer diagnosed in males and the second in females. There are heterogeneous causes of colon cancer development occurring at the molecular level, involving epigenomic and genomic instabilities, resulting in the deregulations of various signaling pathways involved in cell differentiation and growth.[2] Despite thousands of mutant genes, 15 driver mutations were identified as key features in the pathogenesis of colon cancer.[3]
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