Table 4.

Summary of literature describing miRNA expression changes in BE/EAC

Sample sizeUpregulated in BE/EACDownregulated in BE/EACRef.
71 (BE-12, Barrett's esophagus without dysplasia-20, LGD-27, EAC/HGD-12)miR-192 (P < 0.00001), miR-196a (P < 0.05): upregulated in Barrett's esophagus as compared with healthy tissue.miR-196a expression is correlated with progression from IM-LGD-HGD-EAC (P < 0.005).miR203 (P < 0.00001): downregulation in Barrett's esophagus as compared with healthy tissue.(209)
22 (Barrett's esophagus without dysplasia-11, Barrett's esophagus with dysplasia-11)miR-15b (3.3-fold; P < 0.05), miR-203 (5.7-fold; P < 0.05): upregulated in dysplasia as compared with nondysplastic Barrett's esophagus.miR-486-5p (4.8-fold; P < 0.05), miR-let-7a (3.3-fold; P < 0.05): downregulated in dysplasia as compared with nondysplastic Barrett's esophagus.(110)
100 (EAC-100, adjacent normal tissue as control)miR-21 (∼3-fold; P < 0.05), miR-223 (∼2-fold; P < 0.05), miR-192 (∼3.5-fold; P < 0.05), and miR-194 (∼3.5-fold; P < 0.05): upregulated in EAC as compared with adjacent normal tissue.miR-203 (∼3-fold; P < 0.05): downregulated in EAC as compared with adjacent normal tissue.(111)
25 (Healthy-9, BE-5, HGD-1, EAC-10)miR-192 (1.7-fold; FDR < 1 e−07), miR-194 (2-fold; FDR < 1e−07), miR-21 (3.7-fold; FDR = 0.0003), miR-200c (1.9-fold; FDR = 0.0015), miR-93 (1.3-fold; FDR = 0.0108): upregulated in EAC as compared with Barrett's esophagus.miR-27b (1.43-fold; FDR = 0.0003), miR-342 (1.25-fold; FDR = 0.0015), miR-125b (2-fold; FDR = 0.0108), miR-100 (1.25-fold; FDR = 0.011): downregulated in EAC as compared with Barrett's esophagus.(104)
75 (Healthy-15, BE-15, LGD-15, HGD-15, EAC-15)miR-215 (62.8-fold; P < 1e−07), miR-192 (6.34-fold; P < 1e−07): upregulated in Barrett's esophagus in comparison with normal tissue and remained at similar levels with disease progress.miR-205 (10-fold; P = 1.39e−0.5), let-7c (2.04-fold; P = 3.11e−05), miR-203 (6.67-fold; P = 3.2e−0.5): downregulated in Barrett's esophagus in comparison with normal tissue and remained at similar levels as disease progresses.(114)
91 (LGD-31, HGD-29, EAC-31, In all cases adjacent normal tissue used as a control)miR-200a (13.5-fold; P = 0.02), miR-513 (1.58-fold; P = 0.03), miR-125b (9.2-fold; P = 0.04), miR-101 (1.83-fold; P = 0.04), miR-197 (1.61-fold; P = 0.04): upregulated in LGD to HGD transition.miR-23b (1.45-fold; P = 0.007), miR-20b (1.56-fold; P = 0.01), miR-181b (2.22-fold; P = 0.03), miR-203 (1.49-fold; P = 0.03), miR-193b (2.70-fold; P = 0.04), miR-636 (4.17-fold; P = 0.04): downregulated in LGD to HGD transition. let-7a (1.75-fold; P = 0.01), let-7b (1.59-fold; P = 0.009), let-7c (1.69-fold; P = 0.03), let-7f (1.69-fold; P = 0.03), miR-345 (2-fold; P = 0.02), miR-494 (1.72-fold; P = 0.03), miR-193a (2.27-fold; P = 0.05): downregulated in HGD-EAC development process.(112)
48 (BE-19, EAC-29)miR-21 (∼2.8-fold; P < 0.05), miR-143 (∼11.3-fold; P < 0.05), miR-145 (∼3.4-fold; P < 0.05), miR-194 (∼126-fold; P < 0.05), miR-215 (∼18-fold; P < 0.05): upregulated in Barrett's esophagus as compared with adjacent normal tissue.miR-203 (∼17-fold; P < 0.05), miR-205 (∼175-fold; P < 0.05): downregulated in Barrett's esophagus as compared with adjacent normal tissue.miR-143 (∼3-fold; P < 0.05), miR-145 (∼1.8-fold; P < 0.05), miR-215 (∼3.1-fold; P < 0.05): Lower expression in EAC as compared with Barrett's esophagus.(109)
49 (IM-15, HGD-14, and EAC-20, adjacent normal tissue)miR-31 (>4-fold; P < 0.02), miR-375 (>4-fold; P < 0.001): downregulated in transition from Barrett's esophagus to EAC.(210)
37 (BE-17, EAC-20, 9 adjacent normal tissue samples)miR-141 (∼2-fold; P = 0.0126), miR-200a (∼2.5-fold; P = 0.0001), miR-200b (∼2.1-fold; P < 0.0001), miR-200c (∼1.9-fold; P = 0.0014), miR-429 (∼1.8-fold; P = 0.0031): underexpressed in EAC as compared with Barrett's esophagus.(105)
11 (EAC-11, different lesions were collected from these patients and classified into Barrett's esophagus, LGD, HGD, and EAC)miR-196a is overexpressed in early EAC (151-fold) > HGD (62.2-fold; P = 0.00002) > LGD (31.1-fold; P = 0.0005) > Barrett's esophagus (28.9-fold; P = 0.00001). Fold changes are calculated as compared with normal epithelium.(107)
45 (patients with EAC undergoing surgery)miR-143 (P = 0.0148), miR-199a_3p (P = 0.0009), miR-199a_5p (P = 0.0129), miR-100 (P = 0.0022) and miR-145 (P = 0.1176) expression predicted a worse survival followed by esophagectomy.Overexpression of miR-199a_3p/_5p and miR-99b was associated with lymphnode metastasis.Downregulation of miR-143 (P = 0.0049) and miR-145 (P = 0.0069) in EAC as compared with adjacent normal tissue.(211)
24 (BE-24, progression to EAC-7, not progressed to EAC-17 in at least 5-y follow-up)miR-192 (ROC AUC = 0.61), 194 (ROC AUC = 0.70), 196a (ROC AUC = 0.80), and 196b (ROC AUC = 0.74) showed significantly higher expression in Barrett's esophagus samples from patients who progressed to EAC as compared with those who did not progress to EAC.(212)
5 (patients with EAC undergoing surgery. Adjacent benign tissue as a control)miR-296 is overexpressed ∼2-fold in EAC as compared with adjacent benign tissue.(213)
22 patients with locally advanced EAC tumor undergoing surgeryNegative association between miR-148a expression and tumor differentiation (P < 0.001). Significantly higher expression of miR-148a in tumors located in the lower esophagus as compared with tumors in the middle esophagus (P = 0.021).(214)
99 EAC patient tissue samples undergoing surgerymiR-30e (P = 0.002) and miR-200a (P = 0.044) expression were associated with poor overall survival. miR-16-2 (P = 0.027) and miR-30e (P = 0.002) expression were associated with poor disease-free survival.(215)

NOTE: Wherever needed, fold-change values are calculated/adapted from the expression/fold-change values described in the original article to have uniform format for the purpose of this review.