Table 1.
Characteristics of the studies included in the meta-analysis
| TUMOR SITE | PATIENT POPULATION | HtrA1 | RESULTS | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Cancer and Normal-looking | Healthy controls | Setting | Laboratory | Normalization | |||||
| Tumor Marker | Prognostic Marker | Protein | mRNA | Housekeeping | Healthy tissues | ||||
| Colo-rectum [13] |
N = 37 M = 22 F = 15 mean age ± sd 65.5 ± 9.4 |
N = 36 M = 13 F = 23 mean age ± sd 53.3 ± 10.0 |
✓ | ✓ | ✓ | Differences between cancer and healthy control tissue p = 0.0001 Difference between cancer and normal-looking tissue p = 0.001 |
|||
| Liver [12] |
N = 60 M = 25 F = 35, mean age 51.5 |
– | ✓ | – | – | ✓ | ✓ GADPH |
Difference between cancer and normal-looking tissue p < 0.0001 | |
| Stomach [34] |
N = 42 M = 22 mean age ± sd 53.4 ± 9.9 F = 20 mean age ± sd 50.3 ± 14.1 |
– | ✓ | – | – | ✓ | ✓ B-ACTIN |
Normal gastric tissue, positive staining 83.3% Tumor tissue, negative staining 95.0% |
|
| Bladder [17] |
N = 68, M = 50 F = 18 mean age ± sd 68.2 ± 7.0 |
– | ✓ | – | ✓ | ✓ | ✓ B-ACTIN |
✓ | Difference between cancer and normal-looking tissue p < 0.0001 for protein. Difference for mRNA not significant p = 0.422 |
| Breast [11] |
N = 131 all females | – | – | ✓ | ✓ | ✓ GADPH |
Better survival in high expression OS HR 0.45 (0.23–0.90) p = 0.023 | ||
| Esophagus [Yu] [35] |
N = 63 M = 50 F = 10 mean age 73.4 range 45–79 |
– | ✓ | – | ✓ | ✓ | ✓ GADPH B-ACTIN |
✓ | Difference between cancer and normal-looking tissue p < 0.05 as protein, p = 0.004 as mRNA |
| Esophagus [Xia] [36] |
N = 115 Age < 60 N = 52 Age > 60 N = 63 |
– | ✓ | ✓ | ✓ | ✓ | ✓ B-ACTIN |
Difference between cancer and normal-looking tissue p < 0.05 both protein and mRNA | |
| Better survival in high expression OS: HR 0.75 (95 CI 0.38–1.4) p = 0.433a | |||||||||
| Liver [37] |
N = 50 M = 42 mean age ± sd 52.4 ± 9.9 F = 8 mean age ± sd 50.3 ± 14.1 |
– | ✓ | ✓ | ✓ | – | – | ✓ | Difference between cancer and normal-looking tissue p = 0.45 |
| Better survival in high expression: OS: HR 0.59 (95 CI 0.14–2.37) p = 0.486a | |||||||||
| Stomach [38] |
N = 80 M = 51, F = 29 mean age, 64 range, 32–82 |
– | ✓ | ✓ | ✓ | OS: HR 0.55 (95% CI 0.32–0.96) p = 0.037 | |||
| Thyroid [9] |
N = 20 age not reported | ✓ | ✓ | ✓ | ✓ GADPH |
Not statistically significant | |||
| Endometrium [Mullany] [10] |
N = 184 mean age ± sd 66.1 ± 11.3 |
– | ✓ | ✓ | ✓ B-ACTIN |
OS HR: 0.29 (95% CI 0.023–3.75) p = 0.037 | |||
| Endometrium [Narkiewicz] [39] |
N = 36 all females, age not reported | N = 88 all females, age not reported | ✓ | ✓ | ✓ | ✓ B-ACTIN |
Difference between cancer and healthy control tissue p < 0.0001 | ||
| Endometrium [Bowden] [40] |
N = 15 all females, age not reported | N = 4 all females, age not reported | ✓ | ✓ | ✓ GADPH |
HtrA1 mRNA significantly lower in tumor than in normal endometrium (p < 0.0001) | |||
| Pleura [15] |
N = 70 F = 29, M = 41 median age, 65 range, 45–81 |
– | ✓ | ✓ | ✓ | HtrA1 (+): HR 1 (reference category) HtrA1 (++): HR 0.65 (95% CI 0.348–0.876) HtrA1 (+++): HR 0.26 (95% CI 0.122–0.454) p < 0.00 | |||
| Ovary [41] |
N = 44 all females, age not reported | N = 19 all females, age not reported | ✓ | ✓ | ✓ | ✓ B-ACTIN |
HtrA1 mRNA significantly decreased in tumor compared with normal ovarian tissue (p < 0.0001) but not for HtrA1 protein (p = 0.452) | ||
M Males, F Females, (y) years, sd standard deviation, OS overall survival
aThe hazard ratio (HR) and 95% Confidence Interval (CI) were used as a measure of effect size. When the HR and 95% CI were not reported in the publications, they were estimated from the Kaplan-Meier curves according to Parmar et al. [28], Tierney et al. [29], and Williamson et al. [30]