Potential Non-Invasive Biomarkers for Early Diagnosis of Oral Squamous Cell Carcinoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants and Sample Collection
2.2. Multiplex Immunoassay
2.3. Statistical Analysis
3. Results
3.1. Salivary Cytokine Levels in OL, OSCC Patients, and Healthy Controls
3.2. Correlation among Salivary Cytokine Levels and Association with Clinicopathological Characteristics of OSCC Patients
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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Early | Advanced | ||||
---|---|---|---|---|---|
Control | HL | PVL | OSCC | OSCC | |
Age (median ± SD) | 62 ± 8.3 | 68 ± 12.1 | 67 ± 12.3 | 73 ± 10.9 | 65 ± 15.6 |
Sex | |||||
Male | 9 (36%) | 10 (30.3%) | 13 (39.4%) | 13 (39.4%) | 20 (60.6%) |
Female | 16 (64%) | 23 (69.7%) | 20 (60.6%) | 20 (60.6%) | 13 (39.4%) |
Tobacco smoking status | |||||
Non-smokers | 21 (84%) | 15 (45.5%) | 24 (72.7%) | 23 (69.7%) | 14 (42.4%) |
Current smokers | 4 (16%) | 18 (54.5%) | 9 (27.3%) | 10 (30.3%) | 19 (57.6%) |
Clinical form | |||||
Homogeneous white plaque/s | 33 (100%) | ||||
Verrucous | 14 (42.4%) | ||||
Homogeneous and verrucous regions | 19 (57.6%) | ||||
Erythroplakic | - | 6 (18.7%) | 1 (3%) | ||
Exophytic | 7 (21.8%) | 1 (3%) | |||
Ulcerative | 14 (43.7%) | 25 (75.7%) | |||
Mixed | 5 (15.6%) | 6 (18.2%) | |||
Histologic tumor differentiation | |||||
well | 26 (78.8%) | 19 (57.6%) | |||
not well * | 7 (21.2%) | 14 (42.4%) | |||
Neck metastases | |||||
yes | 6 (18.2%) | 26 (78.8%) | |||
no | 27 (81.8%) | 7 (21.2%) |
A | Control (n = 25) | HL (n = 33) | PVL (n = 33) | pa | |
---|---|---|---|---|---|
IL-1α | 1227.24 ± 122.90 | 1768.11 ± 376.97 | 1886.48 ± 294.87 | ns | |
IL-6 | 7.95 ± 0.95 | 22.61 ± 4.78 | 18.90 ± 3.75 | 0.001 ** | |
IL-8 | 526.17 ± 59.03 | 1382.92 ± 279.60 | 1140.87 ± 240.48 | 0.004 ** | |
IP-10 | 884.97 ± 93.39 | 1649.98 ± 386.48 | 1157.80 ± 251.30 | ns | |
MCP-1 | 1066.61 ± 126.54 | 2535.35 ± 372.84 | 3600.83 ± 481.32 | 0.001 ** | |
TNF-α | 7.62 ± 0.84 | 19.65 ± 2.82 | 23.08 ± 4.26 | 0.001 ** | |
HCC-1 | 75.36 ± 6.10 | 174.55 ± 27.66 | 189.28 ± 35.77 | 0.002 ** | |
PF-4 | 253.74 ± 23.98 | 293.92 ± 60.53 | 454.78 ± 146.61 | ns | |
B | Early OSCC (n = 33) | Advanced OSCC (n = 33) | pb | pc | pd |
IL-1α | 1556.19 ± 248.31 | 1313.79 ± 189.58 | ns | ns | ns |
IL-6 | 99.82 ± 26.09 | 262.08 ± 65.83 | <0.001 ** | <0.001 ** | 0.01 ** |
IL-8 | 2567.01 ± 549.72 | 4124.81 ± 787.23 | <0.001 ** | 0.05 * | ns |
IP-10 | 1963.89 ± 365.41 | 1556.53 ± 332.42 | ns | ns | ns |
MCP-1 | 2560.73 ± 370.26 | 2099.76 ± 429.95 | 0.003 ** | ns | ns |
TNF-α | 59.82 ± 11.56 | 122.52 ± 20.68 | <0.001 ** | <0.001 ** | 0.01 ** |
HCC-1 | 298.53 ± 49.55 | 551.32 ± 119.67 | <0.001 ** | 0.01 ** | ns |
PF-4 | 642 ± 104.85 | 1021.85 ± 220.02 | 0.01 ** | <0.001 ** | ns |
A Diagnostic Parameters | IL-6 | IL-8 | TNF-α | HCC-1 | PF-4 |
---|---|---|---|---|---|
AUC | 0.820 | 0.702 | 0.819 | 0.714 | 0.731 |
p | <0.0001 | <0.0001 | <0.0001 | <0.0001 | <0.0001 |
SE a | 0.037 | 0.046 | 0.036 | 0.045 | 0.043 |
YI | 0.560 | 0.363 | 0.500 | 0.363 | 0.348 |
Cut-off value (pg/mL) | >38.314 | >1281.38 | >34.08 | >159.19 | >129 |
Sensitivity % | 66.67 | 63.64 | 66.67 | 71.21 | 92.42 |
Specificity % | 89.39 | 72.73 | 83.33 | 65.15 | 42.42 |
95% CI b | 0.744–0.882 | 0.616–0.778 | 0.742–0.880 | 0.629–0.789 | 0.647–0.804 |
B Diagnostic Parameters | IL-6 | IL-8 | TNF-α | HCC-1 | PF-4 |
AUC | 0.921 | 0.842 | 0.953 | 0.898 | 0.710 |
p | <0.0001 | <0.0001 | <0.0001 | <0.0001 | 0.002 |
SE a | 0.026 | 0.040 | 0.019 | 0.032 | 0.053 |
YI | 0.778 | 0.677 | 0.863 | 0.753 | 0.436 |
Cut-off value (pg/mL) | >15.038 | >923.78 | >17.01 | >112.909 | >308 |
Sensitivity % | 81.82 | 75.76 | 86.36 | 83.33 | 63.64 |
Specificity % | 96.00 | 92.00 | 100 | 92.00 | 80.00 |
95% CI b | 0.849–0.969 | 0.616–0.778 | 0.886–0.986 | 0.886–0.9 | 0.605–0.800 |
A | Control | |||||
---|---|---|---|---|---|---|
IL-8 | MCP-1 | TNF-α | HCC-1 | PF-4 | ||
IL-α | Pearson correlation | * 0.426 | * 0.458 | |||
Sig. (two-tailed) | 0.03 | 0.02 | ||||
IL-6 | Pearson correlation | ** 0.593 | * 0.493 | *** 0.817 | * 0.438 | |
Sig. (two-tailed) | 0.002 | 0.01 | <0.001 | 0.03 | ||
IL-8 | Pearson correlation | *** 0.706 | * 0.512 | |||
Sig. (two-tailed) | <0.001 | 0.01 | ||||
TNF-α | Pearson correlation | * 0.463 | ||||
Sig. (two-tailed) | 0.02 | |||||
HCC-1 | Pearson correlation | ** 0.601 | ||||
Sig. (two-tailed) | 0.001 | |||||
B | Early OSCC Stages | |||||
IL-8 | MCP-1 | TNF-α | HCC-1 | PF-4 | ||
IL-1α | Pearson correlation | * 0.364 | ** 0.528 | |||
Sig. (two-tailed) | 0.04 | 0.002 | ||||
IL-6 | Pearson correlation | ** 0.478 | ** 0.456 | |||
Sig. (two-tailed) | 0.005 | 0.008 | ||||
IL-8 | Pearson correlation | ** 0.515 | *** 0.619 | ** 0.522 | * 0.350 | |
Sig. (two-tailed) | 0.002 | <0.001 | 0.002 | 0.05 | ||
MCP-1 | Pearson correlation | * 0.393 | ||||
Sig. (two-tailed) | 0.02 | |||||
TNF-α | Pearson correlation | *** 0.595 | ||||
Sig. (two-tailed) | <0.001 | |||||
C | Advanced OSCC Stages | |||||
IP-10 | MCP-1 | TNF-α | HCC-1 | PF-4 | ||
IL-6 | Pearson correlation | ** 0.457 | *** 0.568 | |||
Sig. (two-tailed) | 0.007 | <0.001 | ||||
IL-8 | Pearson correlation | *** 0.549 | *** 0.558 | *** 0.738 | ||
Sig. (two-tailed) | <0.001 | <0.001 | <0.001 | |||
MCP-1 | Pearson correlation | *** 0.569 | ** 0.495 | |||
Sig. (two-tailed) | <0.001 | 0.003 | ||||
HCC-1 | Pearson correlation | * 0.369 | ||||
Sig. (two-tailed) | 0.03 |
A Advanced OSCC Stages | |||||
---|---|---|---|---|---|
Mean | L | U | P (Advanced OSCC) | P (Early OSCC) | |
IL-1α | 1703.27 | 1690.87 | 1715.66 | 0.512 (±0.07) | 0.483 (±0.07) |
IL-6 | 324.00 | 319.08 | 328.92 | 0.763 (±0.06) | 0.235 (±0.07) |
IP-10 | 2195.84 | 2175.20 | 2216.47 | 0.555 (±0.07) | 0.455 (±0.06) |
MCP-1 | 2674.38 | 2654.15 | 2694.60 | 0.486 (±0.06) | 0.53 (±0.06) |
TNF-α | 156.37 | 155.13 | 157.60 | 0.772 (±0.06) | 0.228 (±0.07) |
HCC-1 | 573.70 | 568.87 | 578.52 | 0.575 (±0.06) | 0.422 (±0.06) |
PF-4 | 994.85 | 986.26 | 1003.43 | 0.529 (±0.07) | 0.456 (±0.07) |
B Neck Metastases (NM) | |||||
Mean | L | U | P (Present NM) | P (Absent NM) | |
IL-1α | 1706.22 | 1694.38 | 1718.06 | 0.582 (±0.06) | 0.421 (±0.06) |
IL-6 | 313.45 | 308.94 | 317.97 | 0.817 (±0.06) | 0.181 (±0.06) |
IP-10 | 2171.82 | 2152.56 | 2191.08 | 0.606 (±0.06) | 0.387 (±0.07) |
MCP-1 | 2884.44 | 2864.18 | 2904.69 | 0.569 (±0.07) | 0.423 (±0.06) |
TNF-α | 136.34 | 135.25 | 137.43 | 0.732 (±0.07) | 0.275 (±0.07) |
HCC-1 | 559.69 | 555.16 | 564.22 | 0.634 (±0.06) | 0.355 (±0.06) |
PF-4 | 1024.75 | 1016.33 | 1033.18 | 0.607 (±0.06) | 0.384 (±0.06) |
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Dikova, V.; Jantus-Lewintre, E.; Bagan, J. Potential Non-Invasive Biomarkers for Early Diagnosis of Oral Squamous Cell Carcinoma. J. Clin. Med. 2021, 10, 1658. https://doi.org/10.3390/jcm10081658
Dikova V, Jantus-Lewintre E, Bagan J. Potential Non-Invasive Biomarkers for Early Diagnosis of Oral Squamous Cell Carcinoma. Journal of Clinical Medicine. 2021; 10(8):1658. https://doi.org/10.3390/jcm10081658
Chicago/Turabian StyleDikova, Valentina, Eloisa Jantus-Lewintre, and Jose Bagan. 2021. "Potential Non-Invasive Biomarkers for Early Diagnosis of Oral Squamous Cell Carcinoma" Journal of Clinical Medicine 10, no. 8: 1658. https://doi.org/10.3390/jcm10081658