Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study
Abstract
1. Introduction
2. Materials and Methods
2.1. Participants’ Selection and Sampling
2.2. Hematologic Parameters
2.3. RNA Extraction
2.4. Reverse Transcription
2.5. Digital Droplet PCR
2.6. Serum LCN-2, MMP-9, and MMP-9/NGAL Complex Analysis
2.7. Statistical Analysis
3. Results
3.1. General Description of the Enrolled Individuals
3.2. Hematologic Parameters
3.3. Tissue LCN-2 and MMP-9 Gene Expression
3.4. Serum LCN-2, MMP-9, and MMP-9/NGAL Complex
3.5. Spearman’s Correlation
4. Discussion
5. Conclusions and Perspectives
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient ID# | Sex | Age (Years) | Cancer District | p/cTNM | Serum Sampling (Yes/No) | Tissue Sampling (Yes/No) | |
---|---|---|---|---|---|---|---|
Peri- Tumoral | Tumoral | ||||||
1 | M | 60 | Hypopharynx | cT4bN3bM0 | Yes | No | No |
2 | F | 57 | Hypopharynx | pT4aN0M0 | Yes | No | No |
3 | M | 72 | Larynx | pT4aN0M0 | Yes | No | No |
4 | M | 58 | Hypopharynx | pT3N3bM0 | Yes | No | No |
5 | M | 54 | Larynx | pT3N3bM0 | Yes | No | No |
6 | M | 63 | Larynx | pT4aN0M0 | Yes | Yes | No |
7 | M | 57 | Tongue | pT3N1M0 | Yes | Yes | No |
8 | M | 49 | Larynx | pT3N0M0 | Yes | Yes | No |
9 | M | 66 | Oropharynx | cT4N2bM0 | Yes | No | No |
10 | F | 58 | Tongue | pT3N3bM0 | Yes | Yes | No |
11 | M | 59 | Upper Gingiva | cT4bN2cM1 | Yes | No | No |
12 | M | 60 | Tongue | cT4aN2bM0 | Yes | No | No |
13 | M | 53 | Oropharynx | cT4aN3bM0 | Yes | No | No |
14 | M | 46 | Tongue | pT1N0M0 | Yes | No | No |
15 | M | 65 | Larynx | pT3N0M0 | Yes | No | No |
16 | M | 70 | Larynx | pT4aN3bM0 | Yes | Yes | No |
17 | F | 75 | Larynx | pT3N0M0 | Yes | Yes | No |
18 | M | 56 | Larynx | pT3N0M0 | Yes | Yes | No |
19 | M | 71 | Larynx | pT3N3bM0 | Yes | Yes | No |
20 | F | 60 | Larynx | pT2N0M0 | Yes | Yes | No |
21 | M | 67 | Larynx | pT4aN0M0 | Yes | Yes | No |
22 | M | 78 | Larynx | pT3N0M0 | Yes | Yes | Yes |
23 | M | 56 | Larynx | pT4aN1M0 | Yes | Yes | Yes |
24 | F | 73 | Larynx | pT3N3bM0 | Yes | Yes | Yes |
25 | M | 77 | Larynx | pT3N0M0 | Yes | Yes | Yes |
26 | F | 62 | Larynx | pT2N0M0 | No | Yes | Yes |
27 | M | 69 | Larynx | pT4aN0M0 | No | Yes | Yes |
28 | M | 76 | Larynx | pT2N0M0 | No | Yes | Yes |
29 | M | 65 | Larynx | pT4aN2bM0 | No | Yes | Yes |
30 | M | 60 | Larynx | pT4aN3bM0 | No | Yes | Yes |
Parameter (Range) | Sex | Healthy Controls (n. 20; M16/F4) | Cancer Patients (n. 25; M20/F5) | p-Value | (df), F |
---|---|---|---|---|---|
Glucose (70.3–100.9 mg/dL) | tot | 88.31 ± 2.23 | 113.32 ± 6.46 | 0.002 | (1,42), 10.591 |
M | 87.6 ± 2.51 | 111 ± 19.4 | p(disease) 0.007 p(gender) 0.464 | (1,40) F(disease) 7.99 F(gender) 0.646 | |
F | 91 ± 5.35 | 122 ± 6.71 | |||
UREA (10.20–49.80 mg/dL) | tot | 16.94 ± 1.15 | 31.8 ± 3.51 | <0.001 | (1,42), 12.749 |
M | 17.45 ± 1.29 | 30.47 ± 3.85 | p(disease) 0.002 p(gender) 0.686 | (1,40) F(disease) 11.41 F(gender) 0.16 | |
F | 15 ± 2.64 | 37.18 ± 8.92 | |||
Phosphate (2.80–4.60 mg/dL) | tot | 3.12 ± 0.10 | 3.52 ± 0.10 | 0.01 | (1,42), 7.364 |
M | 2.98 ± 0.09 | 3.46 ± 0.103 | p(disease) 0.081 p(gender) 0.006 | (1,40) F(disease) 3.215 F(gender) 8.468 | |
F | 3.65 ± 0.17 | 3.78 ± 0.32 | |||
Protein (60–82 g/L) | tot | 72.05 ± 0.83 | 66.6 ± 1.58 | 0.007 | (1,42), 7.911 |
M | 71.2 ± 0.87 | 66.35 ± 1.86 | p(disease) 0.013 p(gender) 0.301 | (1,40) F(disease) 6.806 F(gender) 1.097 | |
F | 72.25 ± 1.55 | 67.4 ± 2.89 | |||
Albumin (35–55 g/L) | tot | 44.16 ± 0.57 | 40.64 ± 1.19 | 0.03 | (1,42), 5.072 |
M | 43.9 ± 0.71 | 40.1 ± 1.44 | p(disease) 0.130 p(gender) 0.340 | (1,40) F(disease) 2.393 F(gender) 0.933 | |
F | 45 ± 0.41 | 42.8 ± 3.0 | |||
Bilirubin–Direct (<0.20 mg/dL) | tot | 0.15 ± 0.02 | 0.31 ± 0.04 | 0.002 | (1,42), 10.481 |
M | 0.15 ± 0.03 | 0.32 ± 0.05 | p(disease) 0.013 p(gender) 0.832 | (1,40) F(disease) 6.729 F(gender) 0.05 | |
F | 0.13 ± 0.02 | 0.31 ± 0.05 | |||
Iron (64.8–174.90 ug/dL) | tot | 97.89 ± 5.84 | 75.14 ± 9.17 | 0.059 | (1,42), 3.775 |
M | 99.73 ± 7.24 | 78.28 ± 10.70 | p(disease) 0.09 p(gender) 0.410 | (1,40) F(disease) 2.883 F(gender) 0.694 | |
F | 91 ± 6.10 | 78.28 ± 10.70 | |||
PCR (100–6000 ug/L) | tot | 1392 ± 319 | 29212± 11387 | 0.04 | (1,42), 4.372 |
M | 1673 ± 274 | 32955 ± 13990 | p(disease) 0.197 p(gender) 0.587 | (1,40) F(disease) 1.721 F(gender) 0.300 | |
F | 2350 ± 1211 | 14240 ± 10081 | |||
Transferrin (2.15–3.65 g/L) | tot | 2.76 ± 0.10 | 2.23 ± 0.11 | 0.001 | (1,42), 2.999 |
M | 2.70 ± 0.11 | 2.24 ± 0.13 | p(disease) 0.002 p(gender) 0.617 | (1,40) F(disease) 10.808 F(gender) 0.254 | |
F | 2.97 ± 0.19 | 2.17 ± 0.21 | |||
Creatinine (M: 0.70–1.20 mg/Dl F: 0.50–0.9 mg/dL) | M | 1.04 ± 0.02 | 0.85 ± 0.06 | 0.012 | (1,33), 7.112 |
F | 0.78 ± 0.05 | 0.64 ± 0.08 | 0.189 | (1,7), 2.117 | |
gGT (M: 10.00–40.00 U/L F: 7.00–35.00 U/L) | M | 17.88 ± 1.54 | 55 ± 18.24 | 0.01 | (1,33), 3.073 |
F | 16.25 ± 4.25 | 26.6 ± 3.72 | 0.109 | (1,7), 3.374 | |
LDH (M: 135.00–225.00 U/L F: 135.00–214.00 U/L) | M | 161.26 ± 8.14 | 129.95 ± 9.28 | 0.02 | (1,33), 5.950 |
F | 173.5 ± 12.63 | 138 ± 28.53 | 0.334 | (1,7), 1.077 | |
CPK (M: 20–200 U/L F:20–180 U/L) | M | 139.27 ± 27.68 | 51.90 ± 12.91 | 0.004 | (1,33), 9.627 |
F | 89.75 ± 13.70 | 30.20 ± 5.40 | 0.003 | (1,7), 19.454 | |
Ferritin (M: 30–400 ug/L F: 15–150 ug/L) | M | 67 ± 10.89 | 402.95 ± 87.45 | 0.002 | (1,33), 10.891 |
F | 61.50 ± 18.40 | 313 ± 76.35 | 0.02 | (1,7), 8.154 |
Spearman’s Correlations in Healthy Controls | ||||||
---|---|---|---|---|---|---|
Variable | LCN-2 | MMP-9/NGAL | MMP-9 | Transferrin | Ferritin | |
LCN-2 | Spearman’s rho | — | ||||
p-value | — | |||||
MMP-9/NGAL | Spearman’s rho | 0.236 | — | |||
p-value | 0.397 | — | ||||
MMP-9 | Spearman’s rho | −0.443 | 0.751 *** | — | ||
p-value | 0.100 | <0.001 | — | |||
Transferrin | Spearman’s rho | 0.524 * | 0.203 | −0.106 | — | |
p-value | 0.040 | 0.418 | 0.674 | — | ||
Ferritin | Spearman’s rho | −0.680 ** | −0.338 | −0.137 | −0.688 ** | — |
p-value | 0.004 | 0.171 | 0.587 | 0.001 | — | |
Spearman’s Correlations in UADT Cancer Patients | ||||||
Variable | LCN-2 | MMP-9/NGAL | MMP-9 | Transferrin | Ferritin | |
LCN-2 | Spearman’s rho | — | ||||
p-value | — | |||||
MMP-9/NGAL | Spearman’s rho | 0.598 ** | — | |||
p-value | 0.002 | — | ||||
MMP-9 | Spearman’s rho | 0.242 | 0.674 *** | — | ||
p-value | 0.242 | <0.001 | — | |||
Transferrin | Spearman’s rho | 0.155 | 0.130 | 0.053 | — | |
p-value | 0.459 | 0.534 | 0.800 | — | ||
Ferritin | Spearman’s rho | −0.400 * | −0.479 * | −0.254 | −0.425 * | — |
p-value | 0.049 | 0.016 | 0.220 | 0.034 | — |
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Cavalcanti, L.; Francati, S.; Ferraguti, G.; Fanfarillo, F.; Peluso, D.; Barbato, C.; Greco, A.; Minni, A.; Petrella, C. Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study. Cells 2025, 14, 506. https://doi.org/10.3390/cells14070506
Cavalcanti L, Francati S, Ferraguti G, Fanfarillo F, Peluso D, Barbato C, Greco A, Minni A, Petrella C. Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study. Cells. 2025; 14(7):506. https://doi.org/10.3390/cells14070506
Chicago/Turabian StyleCavalcanti, Luca, Silvia Francati, Giampiero Ferraguti, Francesca Fanfarillo, Daniele Peluso, Christian Barbato, Antonio Greco, Antonio Minni, and Carla Petrella. 2025. "Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study" Cells 14, no. 7: 506. https://doi.org/10.3390/cells14070506
APA StyleCavalcanti, L., Francati, S., Ferraguti, G., Fanfarillo, F., Peluso, D., Barbato, C., Greco, A., Minni, A., & Petrella, C. (2025). Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study. Cells, 14(7), 506. https://doi.org/10.3390/cells14070506