Abstract
In order to find out the most valuable biomarkers and pathways for diagnosis, therapy and prognosis in colorectal cancer (CRC) we have collected the published CRC biomarkers and established a CRC biomarker database (CBD: http://sysbio.suda.edu.cn/CBD/index.html). In this study, we analysed the single and multiple DNA, RNA and protein biomarkers as well as their positions in cancer related pathways and protein-protein interaction (PPI) networks to describe their potential applications in diagnosis, therapy and prognosis. CRC biomarkers were collected from the CBD. The RNA and protein biomarkers were matched to their corresponding DNAs by the miRDB database and the PubMed Gene database, respectively. The PPI networks were used to investigate the relationships between protein biomarkers and further detect the multiple biomarkers. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were used to analyse biological functions of the biomarkers. AI classification techniques were utilized to further verify the significances of the multiple biomarkers in diagnosis and prognosis for CRC. We showed that a large number of the DNA, RNA and protein biomarkers were associated with the diagnosis, therapy and prognosis in various degrees in the CRC biomarker networks. The CRC biomarkers were closely related to the CRC initiation and progression. Moreover, the biomarkers played critical roles in cellular proliferation, apoptosis and angiogenesis and they were involved in Ras, p53 and PI3K pathways. There were overlaps among the DNA, RNA and protein biomarkers. AI classification verifications showed that the combined multiple protein biomarkers played important roles to accurate early diagnosis and predict outcome for CRC. There were several single and multiple CRC protein biomarkers which were associated with diagnosis, therapy and prognosis in CRC. Further, AI-assisted analysis revealed that multiple biomarkers had potential applications for diagnosis and prognosis in CRC.
Highlights
Colorectal cancer (CRC) is one of the most common types of malignancies and third leading cause of cancer-related death [1]
The CRC biomarkers in functional pathways were further analysed by Gene Ontology (GO) analysis and the results showed GOTable annotation inpathway biological process for diagnosis, and prognosis biomarkers enrichment results for CRCtherapy protein biomarkers (Table 2)
Potential applications of the CRC protein biomarkers in protein-protein interaction (PPI) networks for diagnostic, therapeutic and prognostic biomarkers were further analysed and we found that the most frequent protein biomarkers were associated with CRC prognosis
Summary
Colorectal cancer (CRC) is one of the most common types of malignancies and third leading cause of cancer-related death [1]. In 2017, there were 135 430 individuals who were diagnosed for CRC and Cancers 2019, 11, 172; doi:10.3390/cancers11020172 www.mdpi.com/journal/cancers. Accumulating evidence has shown that the outcome of CRC is clearly dependent on the cancer stage [2,3] and follows the strict rule: early diagnosis with better survival and later diagnosis with worse prognosis [4]. The rule for better cancer therapy is that it is always more complicated to treat the later stages of the cancers than to treat the early cancer patients [5]. We lose the best therapy opportunity for the CRC patients when the golden diagnosis has been missed. Advanced cancer therapeutic techniques have improved the outcome of cancer patients, the individuals with the same types of cancer respond remarkably differently to the same therapies. A group of cancer may respond very well to the therapy, another group may not respond to the same therapy at all and even some patients will die due to the side effects of the therapy
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