Diagnostic and Prognostic Roles of Urine Nectin-2 and Nectin-4 in Human Bladder Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Patients and Methods
2.1. Patient Selection and Data Collection
2.2. Processing of Voided Urine and Serum Samples
2.3. Measurement of Nectins in Urine and Serum
2.4. Immunohistochemical (IHC) Staining Analysis of Tumor Expression of Nectins
2.5. Statistical Analysis
3. Results
3.1. Levels of Urine Nectin-2 and Nectin-4
3.2. Diagnostic Performance of Urine Nectin-2 and Nectin-4
3.3. Prognostic Performance of Urine Nectin-2 and Nectin-4
3.4. Correlation among Urine Nectins, Serum Nectins, and Tumor Nectins in MIBC
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | No. of Cases | Urine Nectin-2 (ng/mL) | Urine Nectin-4 (ng/mL) | |||||
---|---|---|---|---|---|---|---|---|
Median (IQR) | Mean ± SEM | p Value | Median (IQR) | Mean ± SEM | p Value | |||
No. of cases | 122 (100%) | 0.0 (0.0–0.2) | 0.40 ± 0.13 | - | 16.0 (5.8–28.1) | 18.3 ± 1.2 | - | |
Sex | Male | 103 (84%) | 0.0 (0.0–0.26) | 0.43 ± 0.15 | 0.99 † | 15.9 (5.5–28.8) | 18.2 ± 1.4 | 0.75 † |
Female | 19 (16%) | 0.02 (0.0–0.21) | 0.21 ± 0.09 | 16.6 (10.5–26.4) | 18.6 ± 3.0 | |||
Age | 70 yo or less | 51 (42%) | 0.0 (0.0–0.15) | 0.17 ± 0.05 | 0.052 † | 20.4 (9.6–30.3) | 20.5 ± 1.8 | 0.06 † |
71 yo or more | 71 (58%) | 0.04 (0.0–0.40) | 0.56 ± 0.22 | 13.1 (5.2–25.3) | 16.6 ± 1.7 | |||
Urine cytology | Negative | 61 (50%) | 0.0 (0.0–0.21) | 3.0 ± 0.09 | 0.47 † | 18.5 (8.9–27.4) | 18.7 ± 1.5 | 0.42 † |
Positive | 61 (50%) | 0.03 (0.0–0.36) | 5.0 ± 0.25 | 12.8 (5.4–29.9) | 17.8 ± 1.9 | |||
Urine NMP-22 # | Negative (£10 U/mL) | 59 (48%) | 0.0 (0.0–0.15) | 0.18 ± 0.08 | 0.002 † | 17.4 (5.9–27.9) | 18.5 ± 1.7 | 0.72 † |
Positive (>10 U/mL) | 63 (52%) | 0.06 (0.0–0.53) | 0.60 ± 0.24 | 13.4 (5.7–29.8) | 18.0 ± 1.8 | |||
Tumor grade (WHO2004) | Low grade | 41 (34%) | 0.0 (0.0–0.21) | 0.26 ± 0.11 | 0.64 † | 0 | 24.0 ± 1.6 | <0.001 † |
High grade | 81 (66%) | 0.0 (0.0–0.38) | 0.46 ± 0.19 | 9.7 (4.3–24.2) | 15.4 ± 1.6 | |||
Carcinoma in situ | Absent | 75 (61%) | 0.03 (0.0–0.40) | 0.55 ± 0.21 | 0.03 † | 16.6 (8.2–27.5) | 18.7 ± 1.6 | 0.59 † |
Present | 47 (39%) | 0.0 (0.0–0.14) | 0.15 ± 0.05 | 10.5 (5.4–30.3) | 17.5 ± 2.0 | |||
Clinical T category ## | Ta/Tis | 43 (35%) | 0.0 (0.0–0.20) | 0.25 ± 0.11 | 0.07 ‡ | 25.3 (16.9–32.7) | 24.9 ± 1.8 | <0.001 ‡ |
T1 | 35 (29%) | 0.0 (0.0–0.18) | 0.19 ± 0.07 | 24.1 (13.4–32.7) | 24.9 ± 2.4 | |||
T2 | 24 (20%) | 0.0 (0.0–0.23) | 0.90 ± 0.62 | 5.4 (3.1–9.5) | 6.1 ± 0.7 | |||
T3 | 14 (11%) | 0.10 (0.0–0.74) | 0.44 ± 0.17 | 6.7 (3.9–10.7) | 7.2 ± 1.1 | |||
T4 | 6 (5%) | 0.28 (0.05–1.23) | 0.55 ± 0.25 | 4.7 (3.1–11.8) | 6.7 ± 1.9 | |||
Muscle invasiveness | NMIBC (Ta/Tis/T1) | 78 (64%) | 0.0 (0.0–0.19) | 0.22 ± 0.07 | 0.04 † | 24.7 (16.6–32.7) | 24.9 ± 1.4 | <0.001 † |
MIBC (T2-4) | 44 (36%) | 0.05 (0.0–0.52) | 0.70 ± 0.34 | 5.4 (3.3–9.7) | 6.5 ± 0.6 |
Performance Characteristics | Urine Nectin-2 | Urine Nectin-4 | NMP-22 | VUC | ||
---|---|---|---|---|---|---|
Control vs. BCa | NMIBC vs. MIBC | Control vs. BCa | NMIBC vs. MIBC | Control vs. BCa | Control vs. BCa | |
AUROC | 0.56 | 0.60 | 0.94 | 0.92 | - | - |
Cutoff value | 0.53 ng/mL † | 0.011 ng/mL † | 1.64 ng/mL † | 12.0 ng/mL † | 10 U/mL ‡ | - |
Sensitivity (%) | 84 (77–90) | 61 (46–74) | 98 (93–99) | 91 (79–96) | 52 (43–60) | 47 (38–56) |
Specificity (%) | 40 (17–69) | 61 (50–72) | 80 (49–96) | 86 (76–92) | 100 (72–100) | 100 (72–100) |
Positive predictive value (%) | 95 (89–97) | 47 (35–60) | 98 (94–99) | 78 (65–88) | 100 (94–100) | 100 (94–100) |
Negative predictive value (%) | 17 (7.0–37) | 74 (52–83) | 73 (43–90) | 94 (86–98) | 14 (8.1–25) | 13 (7.4–23) |
Accuracy (%) | 81 | 57 | 96 | 81 | 55 | 51 |
McNemar test, p value for comparison with VUC | p < 0.001 | - | p < 0.001 | - | p = 0.50 | - |
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Miyake, M.; Nishimura, N.; Ohnishi, S.; Oda, Y.; Owari, T.; Ohnishi, K.; Morizawa, Y.; Hori, S.; Gotoh, D.; Nakai, Y.; et al. Diagnostic and Prognostic Roles of Urine Nectin-2 and Nectin-4 in Human Bladder Cancer. Cancers 2023, 15, 2565. https://doi.org/10.3390/cancers15092565
Miyake M, Nishimura N, Ohnishi S, Oda Y, Owari T, Ohnishi K, Morizawa Y, Hori S, Gotoh D, Nakai Y, et al. Diagnostic and Prognostic Roles of Urine Nectin-2 and Nectin-4 in Human Bladder Cancer. Cancers. 2023; 15(9):2565. https://doi.org/10.3390/cancers15092565
Chicago/Turabian StyleMiyake, Makito, Nobutaka Nishimura, Sayuri Ohnishi, Yuki Oda, Takuya Owari, Kenta Ohnishi, Yosuke Morizawa, Shunta Hori, Daisuke Gotoh, Yasushi Nakai, and et al. 2023. "Diagnostic and Prognostic Roles of Urine Nectin-2 and Nectin-4 in Human Bladder Cancer" Cancers 15, no. 9: 2565. https://doi.org/10.3390/cancers15092565