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Review
. 2021 Feb 3;29(2):587-596.
doi: 10.1016/j.ymthe.2020.12.017. Epub 2020 Dec 15.

Novel Genetic and Epigenetic Biomarkers of Prognostic and Predictive Significance in Stage II/III Colorectal Cancer

Xiao-Jing Luo  1 , Qi Zhao  1 , Jia Liu  1 , Jia-Bo Zheng  1 , Miao-Zhen Qiu  1 , Huai-Qiang Ju  1 , Rui-Hua Xu  2
Affiliations
Review

Novel Genetic and Epigenetic Biomarkers of Prognostic and Predictive Significance in Stage II/III Colorectal Cancer

Xiao-Jing Luo et al. Mol Ther. .

Abstract

The therapeutic strategies of stage II/III colorectal cancer (CRC) patients after curative surgery remain controversial. In the clinical decision-making process, oncologists need to answer questions such as whether adjuvant chemotherapy is necessary or which therapeutic regimen should be given to each patient. At present, whether adjuvant chemotherapy should be applied is primarily based on histopathological features and clinical risk factors. However, only a fraction of patients can benefit from it. More rigorous stratifying biomarkers are urgently needed to help further distinguishing these populations of patients. Recent progress in next-generation sequencing and high-throughput technologies has greatly promoted biomarker discovery as well as our understanding of the underlying mechanisms in CRC. Novel genetic and epigenetic biomarkers that are associated with prognosis or therapeutic responses have emerged. In this review, we discuss the strategies of biomarker discovery and summarize the status and assess the utility of previously published biomarkers in CRC.

Keywords: biomarker; circRNA; colorectal cancer; epigenetic; genomic; lncRNA; miRNA; non-coding RNA; predictive; prognostic; transcriptomic.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Sequential Progression Model in Colorectal Cancer This is an oversimplified model describing the tumor progression sequence of CRC from adenoma to carcinoma. The development of CRC is a stepwise accumulation of genetic and epigenetic events, which align with clinical pathological changes., The loss of APC, gatekeeping gene of CRC tumorigenesis, leads to small adenoma formation. Next, mutations in KRAS promote larger adenomas and gradually early carcinomas. The loss of SMAD family member 4 (SMAD4) and mutations in TP53 as well as PIK3CA are acquired later in carcinoma. These serial alterations in genes that regulate cellular differentiation, proliferation, and apoptosis pathways give rise to CRC carcinogenesis.
Figure 2
Figure 2
Different Categories of Prognostic and Predictive CRC Biomarkers in Bimolecular Level Different categories in the bimolecular level of CRC biomarkers with potential prognostic and predictive values, which include genomic and transcriptomic aspects mainly, are summarized. Also, representative candidate genes that are currently under research subordinate to each category are enumerated.
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