Table 2.
Biomarkers for Risk Stratification in Barrett’s Esophagus
| Biomarker | Baseline to Outcome Histology | Mean or Median Follow-up (Years) | Results | References |
|---|---|---|---|---|
| Protein Markers | ||||
|
| ||||
| p53 | NDBE to HGD/EAC | 6.6 years | Overexpression - RR: 5.6 (95% CI, 3.1–10.3) Loss – RR: 14.0 (95% CI, 5.3–37.2) |
[160] |
|
| ||||
| Gene and DNA content abnormalities | ||||
|
| ||||
| LOH of 17p+9p, DNA abnormalities | NDBE to EAC | 6.7 years | RR: 38.7 (95% CI, 10.8–138.5) | [105] |
| 9p LOH | NDBE to EAC | 5.0 years | RR: 2.6 (95% CI, 1.1–6.0) | [161] |
| 17p LOH | NDBE/LGD to EAC | 3.0 years | RR: 16 (95% CI, 6.2–39) | [100] |
| Aneuploidy/Tetraploidy | NDBE/LGD to EAC | 5.0 years | RR: 11 (95% CI, 5.8–21) | [161] |
| Panel of LGD, abnormal DNA ploidy, and Aspergillus oryzae lectin | NDBE or LGD to EAC | 6.7 years | Baseline LGD – OR: 3.9 (95% CI, 2.4–6.4) Baseline NDBE – OR: 3.3 (95% CI, 1.8–6.00) |
[162] |
|
| ||||
| FISH | ||||
|
| ||||
| FISH panel: P16, P53, Her-2/neu, 20q, and MYC, and chromosomal centromeric probes 7 and 17 to detect aneuploidy | NDBE to EAC | 3.8 years | p16 loss or aneuploidy - RR: 3.2 (95% CI, 1.3–7.9) | [163] |
|
| ||||
| DNA Methylation | ||||
|
| ||||
| Promoter methylation of p16, RUNX3, HPP1 | NDBE to HGD/EAC | 6.3 years | p16 – OR: 1.7 (95% CI, 1.33–2.20), RUNX3 – OR: 1.80 (95% CI, 1.1–2.8) HPP1 – OR: 1.8 (95% CI, 1.1–2.8) |
[104] |
| 8-gene methylation panel (p16, RUNX3, HPP1, NELL1, TAC1, SST, AKAP12, and CDH13) | NDBE to HGD/EAC | 2.0 or 4.0 years | AUC: 0.84, 80% sensitivity, 70% specificity | [164] |
| 4-gene methylation panel (SLC22A18, PIGR, GJA12, and RIN2) | NDBE to EAC | n/a | AUC: 0.99, 94 % sensitivity, 97 % specificity, | [165] |
|
| ||||
| Gene Expression and MicroRNA (miRNA) | ||||
|
| ||||
| miRNAs −192, −194, −196a, and −196b | NDBE to EAC | 4.6 years | 71%–85% sensitivity, 50%–71% specificity | [103] |
|
| ||||
| Genetic and Clonal Diversity | ||||
|
| ||||
| Shannon LOH diversity index | NDBE to EAC | 4.5 years | RR: 11.0 (95% CI, 5.8–21.0) | [166, 167] |
| Mean pairwise divergence by LOH | 5.0 years | RR: 2.15 (95% CI, 1.67–2.77) | ||
| Number of LOH clones | 5.0 years | RR: 1.99 (95% CI, 1.71–2.32) | ||
|
| ||||
| Proliferation and Cell Cycle Markers | ||||
|
| ||||
| Cyclin D | NDBE to EAC | 4.3 years | OR: 6.9 (95% CI, 1.6–29.9) | [168] |
| Mcm2 | NDBE/LGD to HGD/EAC | 6.0 years | OR: 136 (95% CI, 7.5–2464) | [169] |
NDBE, non-dysplastic Barrett’s esophagus; LGD, low-grade dysplasia; HGD, high-grade dysplasia; EAC esophageal adenocarcinoma; LOH loss of heterozygosity; FISH fluorescent in-situ hybridization; RR relative risk; CI confidence interval; AUC area under curve; OR odds ratio.