Theoretical and in silico Analyses Reveal MYC as a Dynamic Network Biomarker in Colon and Rectal Cancer.

Yanqiu Tong,Yang Song,Chuanhui Xia,Shixiong Deng

doi:10.3389/fgene.2020.555540

Yanqiu Tong, Yang Song + Show 2 more

Open Access

https://doi.org/10.3389/fgene.2020.555540

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Abstract

In this article, we make a theoretical and in silico study for uncovering and evaluating biomarkers in colon and rectal cancer (CRC) by the dynamic network biomarker (DNB) theory. We propose a strategy to employ the theoretical concept of UICC TNM classification in CRC. To reveal the critical transition of CRC, the DNB algorithm was implemented to analyze the genome-wide dynamic network through temporal gene expression data. The relationship between gene sets and clinical features was evaluated by weighted gene co-expression network analysis. The results show that MYC was significantly associated with tumor amplification, tumor immune cells, and survival times. The candidate tumor suppressor genes were ZBTB16, MAL, LIFR, and SLIT2. Protein–protein interaction (PPI) analysis shows that these candidate tumor suppressor genes were significant in immune cells. Data from the Human Protein Atlas showed that a high expression of these candidate tumor suppressor genes was associated with favorable prognosis in TNM stages I–IV. In conclusion, this work provides significant and novel information regarding the TNM stage, cause, and consequences of elevated MYC expression in CRC. MYC expression levels had significant negative correlations with tumor suppressor genes and immune cells.

Highlights

Colon and rectal cancer (CRC) is one of the most frequently diagnosed tumor in terms of incidence, and its incidence among young people has increased in recent years (Brenner et al, 2019; Dang et al, 2020)
The dynamic network biomarker (DNB) score increased sharply from stage III and reached the peak at stage IV, so stage III is designated as a critical transition state, which corresponds to the development of a specific stage in CRC
Cancers are often initiated by some key genetic events, such as activated proto-oncogenes or inactive tumor suppressor genes (Casey et al, 2017), so elucidating the underlying molecular mechanism for these events is critically important for diagnosis and treatment in CRC

Summary

Introduction

Colon and rectal cancer (CRC) is one of the most frequently diagnosed tumor in terms of incidence, and its incidence among young people has increased in recent years (Brenner et al, 2019; Dang et al, 2020). Despite the advance technology in CRC screening and treatment strategies such as molecular biomarkers and immune therapy, poor prognosis remains significant (Wang et al, 2019). Lots of complex factors cause the occurrence and the progression of CRC, such as age, family history, gender, region, and tumor stage (Center et al, 2009; Peng et al, 2018; Tong et al, 2018). Colon and rectal cancer is a genetically heterogeneous disease in which several key biomarkers in different tumor stages could play an important function in tumor initiation, growth, and progression (Ciardiello et al, 2019). It is reported that 40% of CRC patients have disease metastases (Tsikitis et al, 2014); 80% of them metastasize to the liver, and the remaining 20% metastasize to other visceral organs (Manfredi et al, 2006), so cancers diagnosed in early stage are important for the prognosis of CRC, but patients diagnosed at later stages are the majority (Dupaul-Chicoine et al, 2015)

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