Identification of Neck Lymph Node Metastasis-Specific microRNA—Implication for Use in Monitoring or Prediction of Neck Lymph Node Metastasis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Patients
2.2. Blood Sample Collection
2.3. RNA Isolation and Quantitative Real-Time PCR
2.4. Pathological Sample Collection
2.5. Statistical Analysis
3. Results
3.1. Clinicopathological Characteristics of Patients with OSCC
3.2. Diagnosis of Primary Neck LN Metastases Using Single miRNA
3.3. Diagnosis of Primary Neck LN Metastases Using Combination of Multiple miRNAs
3.4. Prediction of Late Neck LN Metastases Using Single miRNA
3.5. Prediction of Late Neck LN Metastases Using Combination of Multiple miRNAs
3.6. Examination of miRNA, Serum SCC Antigen, Pathological Factors, and Survival Prognosis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Patients (n = 40) |
---|---|
Age, mean (range) | 67.3 (33–88) |
Sex, n (%) | |
Male | 22 (55) |
Female | 18 (45) |
Location, n (%) | |
Tongue | 21 (52.5) |
Gingiva | 14 (35) |
Oral floor | 4 (10) |
Buccal mucosa | 1 (2.5) |
T classification, n (%) | |
T1 | 4 (10) |
T2 | 16 (40) |
T3 | 7 (17.5) |
T4 | 13 (32.5) |
N classification, n (%) | |
N0 | 28 (70) |
N1 | 5 (12.5) |
N2 | 7 (17.5) |
N3 | 0 (0) |
M classification, n (%) | |
M0 | 40 (100) |
M1 | 0 (0) |
Stage classification, n (%) | |
I | 3 (7.5) |
II | 14 (35) |
III | 8 (20) |
IV | 15 (37.5) |
Vascular invasion, n (%) | |
(+) | 14 (35) |
(−) | 26 (65) |
Lymphatic invasion, n (%) | |
(+) | 3 (7.5) |
(−) | 37 (92.5) |
Perineural invasion, n (%) | |
(+) | 7 (17.5) |
(−) | 33 (82.5) |
YK classification, n (%) | |
1 | 0 (0) |
2 | 1 (2.5) |
3 | 29 (72.5) |
4C | 6 (15) |
4D | 4 (10) |
Local recurrence, n (%) | |
(+) | 7 (17.5) |
(−) | 33 (82.5) |
Late metastasis in neck lymph nodes, n (%) | |
(+) | 10 (25) |
(−) | 28 (70) |
Intra-area recurrence in neck lymph nodes | 2 (5) |
miRNA | Group | AUC | Sensitivity | Specificity | PPV | NPV | Positive | Negative | Fisher’s Test |
---|---|---|---|---|---|---|---|---|---|
(%) | (%) | (%) | (%) | (n) | (n) | (p-Value) | |||
miR-23 | N(+) | 0.63 | 58.3 | 71.4 | 46.7 | 80 | 7 | 5 | 0.0909 |
N(−) | 8 | 20 | |||||||
miR-24 | N(+) | 0.54 | 33.3 | 89.3 | 57.1 | 75.8 | 4 | 8 | 0.168 |
N(−) | 3 | 25 | |||||||
miR-423 | N(+) | 0.69 | 75 | 71.4 | 52.9 | 87 | 9 | 3 | 0.013 |
N(−) | 8 | 20 | |||||||
miR-19a | N(+) | 0.39 | 75 | 39.3 | 34.6 | 78.6 | 9 | 3 | 0.4844 |
N(−) | 17 | 11 | |||||||
miR-19b | N(+) | 0.63 | 83.3 | 57.1 | 45.5 | 88.9 | 10 | 2 | 0.0354 |
N(−) | 12 | 16 | |||||||
miR-20a | N(+) | 0.53 | 91.7 | 35.7 | 37.9 | 90.9 | 11 | 16 | 0.1244 |
N(−) | 18 | 16 | |||||||
miR-22 | N(+) | 0.58 | 83.3 | 53.6 | 43.5 | 88.2 | 10 | 16 | 0.0408 |
N(−) | 13 | 16 | |||||||
miR-122 | N(+) | 0.59 | 83.3 | 46.4 | 40 | 86.7 | 10 | 16 | 0.1523 |
N(−) | 15 | 16 | |||||||
miR-125 | N(+) | 0.7 | 83.3 | 75 | 58.8 | 91.3 | 10 | 16 | 0.0012 |
N(−) | 7 | 16 | |||||||
miR-144 | N(+) | 0.59 | 41.7 | 82.1 | 50 | 76.7 | 5 | 16 | 0.13294 |
N(−) | 5 | 16 | |||||||
miR183 | N(+) | 0.63 | 66.7 | 64.3 | 44.4 | 81.8 | 8 | 16 | 0.0927 |
N(−) | 10 | 16 | |||||||
miR-150 | N(+) | 0.6 | 75 | 57.1 | 42.9 | 84.2 | 9 | 16 | 0.008 |
N(−) | 12 | 16 | |||||||
miR-4419a | N(+) | 0.52 | 91.7 | 28.6 | 35.5 | 88.9 | 11 | 16 | 0.2332 |
N(−) | 20 | 16 | |||||||
miR-5100 | N(+) | 0.64 | 83.3 | 53.6 | 43.5 | 88.2 | 10 | 16 | 0.0408 |
N(−) | 13 | 16 |
Group | Sensitivity | Specificity | PPV | NPV | Positive | Negative | Fisher’s Test | |
---|---|---|---|---|---|---|---|---|
(%) | (%) | (%) | (%) | (n) | (n) | (p-Value) | ||
serum SCC antigen | N(+) | 16.7 | 71.4 | 20 | 66.7 | 2 | 10 | 0.6927 |
(cut-off 1.5) | N(−) | 8 | 20 | |||||
Vascular invasion | N(+) | 50 | 71.4 | 42.9 | 76.9 | 6 | 6 | 0.2808 |
N(−) | 8 | 20 | ||||||
Lymphatic invasion | N(+) | 8.3 | 92.9 | 33.3 | 70.3 | 1 | 11 | 1 |
N(−) | 2 | 26 | ||||||
YK classification | N(+) | 50 | 85.7 | 60 | 80 | 6 | 6 | 0.04 |
(YK1.2.3:positive,4c.4d:negative) | N(−) | 4 | 24 | |||||
miR-PM | N(+) | 100 | 71.4 | 60 | 100 | 12 | 0 | 0.0001 |
N(−) | 8 | 20 |
miRNA | Group | AUC | Sensitivity | Specificity | PPV | NPV | Positive | Negative | Fisher’s Test |
---|---|---|---|---|---|---|---|---|---|
(%) | (%) | (%) | (%) | (n) | (n) | (p-Value) | |||
miR-23 | meta(+) | 0.56 | 100 | 21.4 | 31.3 | 100 | 10 | 0 | 0.1679 |
meta(−) | 22 | 6 | |||||||
miR-24 | meta(+) | 0.58 | 100 | 35.7 | 35.7 | 100 | 10 | 0 | 0.0377 |
meta(−) | 18 | 10 | |||||||
miR-423 | meta(+) | 0.52 | 100 | 25 | 32.2 | 100 | 10 | 0 | 0.1564 |
meta(−) | 21 | 7 | |||||||
miR-19a | meta(+) | 0.47 | 100 | 10.7 | 28.6 | 100 | 10 | 0 | 0.5519 |
meta(−) | 25 | 3 | |||||||
miR-19b | meta(+) | 0.46 | 100 | 17.9 | 30.3 | 100 | 10 | 0 | 0.2984 |
meta(−) | 23 | 5 | |||||||
miR-20a | meta(+) | 0.56 | 100 | 32.1 | 34.5 | 100 | 10 | 0 | 0.0785 |
meta(−) | 19 | 9 | |||||||
miR-22 | meta(+) | 0.39 | 90 | 25 | 30 | 87.5 | 9 | 1 | 0.6533 |
meta(−) | 21 | 7 | |||||||
miR-122 | meta(+) | 0.65 | 60 | 82.1 | 54.5 | 85.2 | 6 | 4 | 0.0193 |
meta(−) | 5 | 23 | |||||||
miR-125 | meta(+) | 0.5 | 90 | 32.1 | 32.1 | 90 | 9 | 1 | 0.2362 |
meta(−) | 19 | 9 | |||||||
miR-144 | meta(+) | 0.52 | 40 | 82.1 | 44.4 | 79.3 | 4 | 6 | 0.2051 |
meta(−) | 5 | 23 | |||||||
miR183 | meta(+) | 0.51 | 100 | 14.3 | 29.4 | 100 | 10 | 0 | 0.5562 |
meta(−) | 24 | 4 | |||||||
miR-150 | meta(+) | 0.49 | 40 | 85.7 | 50 | 80 | 4 | 6 | 0.1701 |
meta(−) | 4 | 24 | |||||||
miR-4419a | meta(+) | 0.54 | 40 | 85.7 | 50 | 80 | 4 | 6 | 0.1701 |
meta(−) | 4 | 24 | |||||||
miR-5100 | meta(+) | 0.69 | 80 | 60.7 | 45 | 85 | 8 | 2 | 0.0625 |
meta(−) | 11 | 17 |
Group | Sensitivity | Specificity | PPV | NPV | Positive | Negative | Fisher’s Test | |
---|---|---|---|---|---|---|---|---|
(%) | (%) | (%) | (%) | (n) | (n) | (p-Value) | ||
serum SCC antigen | meta(+) | 30 | 75 | 30 | 75.7 | 3 | 7 | 1 |
(cut-off 1.5) | meta(−) | 7 | 21 | |||||
Vascular invasion | meta(+) | 60 | 75 | 46.2 | 84 | 6 | 4 | 0.06 |
meta(−) | 7 | 21 | ||||||
Lymphatic invasion | meta(+) | 0 | 89.9 | 0 | 71.4 | 0 | 10 | 0.5519 |
meta(−) | 3 | 25 | ||||||
YK classification | meta(+) | 40 | 82.1 | 44.4 | 79.3 | 4 | 6 | 0.2051 |
(YK1.2.3:positive YK4c.4d:negative) | meta(−) | 5 | 23 | |||||
miRNA index (miR-LM) | meta(+) | 90 | 75 | 56.3 | 95.5 | 9 | 1 | 0.0005 |
meta(−) | 7 | 21 |
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Higashi, Y.; Nakamura, K.; Takaoka, R.; Tani, M.; Noma, Y.; Mori, K.; Yamashiro, K.; Yokoyama, S.; Hamada, T.; Sugiura, T. Identification of Neck Lymph Node Metastasis-Specific microRNA—Implication for Use in Monitoring or Prediction of Neck Lymph Node Metastasis. Cancers 2023, 15, 3769. https://doi.org/10.3390/cancers15153769
Higashi Y, Nakamura K, Takaoka R, Tani M, Noma Y, Mori K, Yamashiro K, Yokoyama S, Hamada T, Sugiura T. Identification of Neck Lymph Node Metastasis-Specific microRNA—Implication for Use in Monitoring or Prediction of Neck Lymph Node Metastasis. Cancers. 2023; 15(15):3769. https://doi.org/10.3390/cancers15153769
Chicago/Turabian StyleHigashi, Yutaro, Kodai Nakamura, Ryota Takaoka, Mika Tani, Yusaku Noma, Kazuki Mori, Kota Yamashiro, Seiya Yokoyama, Tomofumi Hamada, and Tsuyoshi Sugiura. 2023. "Identification of Neck Lymph Node Metastasis-Specific microRNA—Implication for Use in Monitoring or Prediction of Neck Lymph Node Metastasis" Cancers 15, no. 15: 3769. https://doi.org/10.3390/cancers15153769