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Table 1 Summary of the multivariable hazard ratios and 95% CI for eligible biomarkers, organized according to the Hanahan-Weinberg functional capability

From: Systematic review and meta-analysis of tumor biomarkers in predicting prognosis in esophageal cancer

Biomarker Group No. of studies Patients I-V HR(95% CI) D + L HR(95% CI) I2(%)
Angiogenesis       
COX-2 Total(IHC) 6 469 2.00(1.47-2.71) 1.54(0.80-2.98) 75.0
  ESCC 4 234 1.23(0.79-1.93) 0.96(0.39-2.41) 73.5
  EADC 2 235 3.06(2.01-4.65) 3.06(2.01-4.65) 0.0
VEGF Total 18 1476 1.80(1.51-2.14) 1.76(1.38-2.24) 43.5
  ESCC 16 1329 1.85(1.55-2.21) 1.84(1.45-2.33) 38.4
  EADC 1 38 0.37(0.10-1.40) 0.37(0.10-1.40) -
  EC 1 109 1.80(0.70-4.65) 1.80(0.70-4.65) -
  IHC 14 1109 1.59(1.28-1.98) 1.56(1.16-2.12) 43.6
  ELISA 2 179 2.55(1.72-3.79) 2.67(1.57-4.54) 36.8
  RTPCR 2 188 1.90(1.24-2.91) 1.90(1.24-2.91) 0.0
Evading apoptosis       
survivin Total 5 357 1.60(1.23-2.07) 1.90(1.06-3.40) 74.6
  ESCC(IHC) 4 295 1.50(1.15-1.95) 1.57(0.91-2.69) 70.7
  EC(PCR) 1 62 6.60(1.97-22.12) 6.60(1.97-22.12) -
Insensitivity to antigrowth signal       
p21 Total(IHC) 9 858 0.90(0.75-1.08) 1.27(0.75-2.16) 86.4
  ESCC 7 683 0.90(0.74-1.09) 1.28(0.70-2.33) 87.4
  EC 2 175 0.94(0.57-1.53) 1.31(0.22-7.98) 91.2
p27(-) Total(IHC) 7 606 1.44(1.07-1.92) 1.68(0.90-3.12) 76.4
  ESCC 6 478 1.75(1.25-2.44) 1.97(1.00-3.88) 74.6
  EC 1 128 0.75(0.41-1.38) 0.75(0.41-1.38) -
Limitless replicative potential       
cyclin D1 Total 15 1931 1.65(1.41-1.93) 1.73(1.34-2.23) 56.3
  ESCC 12 1295 1.82(1.50-2.20) 1.89(1.44-2.48) 46.2
  EC 3 636 1.37(1.05-1.80) 1.18(0.57-2.45) 77.4
  IHC 13 1735 1.60(1.36-1.88) 1.64(1.26-2.14) 57.9
  PCR 2 196 2.62(1.41-4.89) 2.79(1.27-6.14) 18.5
HER-2 Total 6 1162 1.06(0.88-1.28) 1.37(0.91-2.07) 67.6
  ESCC 1 66 0.92(0.35-2.41) 0.92(0.35-2.41) -
  EADC 3 291 2.15(1.39-3.33) 2.15(1.39-3.33) 0.0
  EC 2 805 0.91(0.73-1.12) 0.93(0.70-1.23) 32.3
  IHC 4 951 0.96(0.78-1.17) 1.17(0.72-1.88) 66.3
  FISH 1 124 1.80(0.90-3.60) 1.80(0.90-3.60) -
  RPPA 1 87 1.97(1.01-3.83) 1.97(1.01-3.83) -
Ki-67 Total(IHC) 5 424 0.84(0.59-1.20) 0.76(0.41-1.42) 62.2
  ESCC 3 308 1.11(0.70-1.78) 1.11(0.70-1.78) 0.0
  EADC 1 59 0.26(0.11-0.60) 0.26(0.11-0.60) -
  EC 1 57 1.03(0.49-2.17) 1.03(0.49-2.17) -
P53 Total 31 2851 1.34(1.21-1.48) 1.33(1.14-1.56) 48.7
  ESCC 20 2063 1.26(1.11-1.42) 1.25(1.03-1.51) 48.7
  EADC 2 97 2.10(1.10-4.03) 2.10(1.10-4.03) 0.0
  EC 9 691 1.53(1.25-1.86) 1.44(1.06-1.94) 50.9
  IHC 22 2122 1.25(1.12-1.40) 1.20(1.02-1.40) 38.5
  PCR-SSCP 5 383 1.75(1.24-2.49) 1.82(0.93-3.56) 70.5
  ELISA 4 346 2.13(1.46-3.09) 2.13(1.46-3.09) 0.0
Tissue invasion and metastasis       
E-cadherin(-) Total 10 1569 1.13(1.06-1.21) 1.30(1.07-1.58) 61.8
  ESCC 7 977 1.12(1.05-1.19) 1.24(0.99-1.56) 67.2
  EADC 1 59 3.30(0.99-10.99) 3.30(0.99-10.99) -
  EC 2 533 1.41(1.05-1.89) 1.41(1.05-1.89) 0.0
  IHC 9 1472 1.28(1.11-1.49) 1.39(1.08-1.80) 60.4
  ELISA 1 97 1.10(1.02-1.18) 1.10(1.02-1.18) -
Serum markers       
SCC-Ag Total(ESCC/EIA) 5 700 1.28(0.97-1.69) 1.28(0.93-1.76) 16.4
  Total 8 1382 1.43(1.27-1.61) 2.65(1.64-4.27) 85.8
  ESCC 3 260 2.05(1.33-3.17) 2.77(1.12-6.86) 68.4
  EC 5 1122 1.39(1.23-1.57) 2.66(1.44-4.92) 90.1
  LPIA 1 262 3.30(2.17-5.01) 3.30(2.17-5.01) -
  IHC 2 110 4.33(2.02-9.24) 4.33(2.02-9.24) 0.0
  ELISA 1 150 1.42(0.83-2.42) 1.42(0.83-2.42) -
  CRP-kit 1 356 1.52(1.05-2.21) 1.52(1.05-2.21) -
  LEHIA 1 291 1.18(1.03-1.36) 1.18(1.03-1.36) -
  INA 1 123 12.12(3.45-42.57) 12.12(3.45-42.57) -
  ITA 1 90 5.07(1.92-13.41) 5.07(1.92-13.41) -
  Total 5 544 0.96(0.95-0.98) 0.91(0.83-1.00) 87.1
  ESCC 2 351 0.54(0.40-0.74) 0.54(0.40-0.74) 0.0
  EC 3 193 0.97(0.95-0.98) 0.96(0.89-1.03) 88.3
  1. NOTE: HR, hazard ratio; CI, confidence interval. Combined HRs are calculated for the fixed effects general inverse variance (I-V) method and random effects model with DerSimonian and Laird (D + L) method. (-), reduced/negative expression show the higher risk in prognosis. IHC, immunohistochemistry; PCR, polymerase chain reaction; SSCP, single-strand conformation polymorphism; ELISA,enzyme-linked immunosorbent assay; LPIA, latex photometric immunoassay; LEHIA, latex-enhanced homogeneous immunoassay; INA, immunonephelometry; ITA, immunoturbidimetry; RIA, radioimmunoassay; EIA, enzyme immunoassay.