Table 2.
Summary of Prognostic Biomarkers
| Biomarker | Explanation |
|---|---|
| Tissue biomarker | |
| BRAF | Comprises the mitogen-activated protein kinase pathway, which is associated with cell differentiation, migration, angiogenesis, and proliferation. [95] BRAF mutation is associated with poorer PFS and OS. [99,100] The analysis of its prognostic role is recommended. [101] |
| MSI | MSI-high tumors have better prognosis than MSI-low tumors. [97,98] MSI CRC patients showed longer OS and DFS than MSS CRC patients. [110] |
| CIMP | The prognostic role of CIMP is unclear. However, the majority of studies reported that CIMP+/CIMP-high CRC patients showed poorer prognosis than CIMP–/CIMP-high CRC patients. [116] |
| APC | APC is associated with FAP and most cases of sporadic CRC. [109] APC mutation can cause unregulated transcription of many oncogenes. [117] Patients with APC mutation and high miR-21 reportedly had shorter OS. [118] |
| p53 | Some studies reported its association with lower DFS, [103] RFS, [121] and OS [122] rates, but others reported no evidence of a prognostic role. [106,107] |
| SMAD4 | SMAD4 mediates the TGF-β superfamily signaling pathway, which is frequently altered in human cancers. [125] Loss of SMAD4 was associated with poor DFS and OS. [129] |
| Blood biomarker | |
| CEA | CEA level is reportedly significantly associated with patient outcomes. [134] Preoperative CEA level was significantly associated with prognosis in patients with CRC metastasized to the liver. [135,136] |
| NLR | Patients with elevated NLR were significantly associated with shorter OS and shorter PFS after treatment. [142] CRC patients with a pretreatment NLR < 5 were more likely to have 5-year OS and DFS. [143] Also, elevated pretreatment NLR was significantly related with poor OS and RFS in patients with liver metastasis. [144] |
| cfDNA | CRC patients with higher cfDNA concentrations showed a higher risk of recurrence and shorter OS. [44,128] Detectable APC, KRAS, and p53 mutations in the serum were significantly associated with a higher rate of postoperative metastasis/recurrence. [146] |
PFS, progression-free survival; OS, overall survival; MSI, microsatellite instability; CRC, colorectal cancer; DFS, disease-free survival; MSS, microsatellite stable; CIMP, cytosine preceding guanine island methylator phenotype; FAP, familial adenomatous polyposis; RFS, relapse-free survival; TGF-β, transforming growth factor-β; NLR, neutrophil-to-lymphocyte ratio.