초록
Background and Objectives
Sirtuins (SIRTs) play important roles in cellular and organismal homeostasis. They have distinct gene expression patterns in various cancers; however, the relationship between SIRT expression and the progression of thyroid cancer is unclear. We investigated the expression of SIRTs in patients with papillary thyroid carcinoma (PTC) and their role as biomarkers for predicting the aggressiveness of this disease.
Materials and Methods
We used immunohistochemical staining to evaluate the expression of SIRT1 and SIRT3 in tumor specimens from 270 patients with PTC. We also evaluated the potential association between SIRT expression and diverse clinicopathological features.
Results
High SIRT1 expression was negatively correlated with lymphovascular invasion, central lymph node metastasis, and lateral lymph node metastasis. Multivariate analyses revealed that high SIRT1 expression was a negative independent risk factor for lateral lymph node metastasis. By contrast, high SIRT3 expression was positively correlated with locoregional recurrence. Interes-tingly, when patients were grouped by tumor SIRT expression patterns, the group with low SIRT1 expression and high SIRT3 expression was correlated with more aggressive cancer phenotypes including central lymph node metastasis and lateral lymph node metastasis.
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Fig. 1.
Immunohistochemical evaluation of sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3) expression in papillary thyroid carcinoma (PTC) tissue. (A) Representative immunohistochemical images of SIRT1. (B) Representative immunohistochemical images of SIRT3. 0: no staining intensity, +1: weak staining intensity, +2: moderate staining intensity, +3: strong staining intensity (magnification ×100)
![ijt-11-143f1.tif](/upload/SynapseXML/1186ijt/thumb/ijt-11-143f1.gif)
Table 1.
Clinicopathologic parameters of patients (n=270)
Table 2.
Relationships between intensity of sirtuin 1 (SIRT1) staining and clinicopathological factors in 270 patients
Variables | No. of patients | SIRT1 | |||
---|---|---|---|---|---|
Low (Grade 1 and 2) | High (Grade 3 and 4) | p value | |||
Age, years | <45 | 104 | 66 | 38 | 0.411 |
≥45 | 166 | 97 | 69 | ||
Gender | Male | 47 | 31 | 16 | 0.389 |
Female | 223 | 132 | 91 | ||
Tumor size | ≤1 cm | 110 | 61 | 49 | 0.171 |
>1 cm | 160 | 102 | 58 | ||
Multicentricity | No | 158 | 96 | 62 | 0.877 |
Yes | 112 | 67 | 45 | ||
Microscopic capsular invasion | No | 71 | 37 | 34 | 0.098 |
Yes | 199 | 126 | 73 | ||
Extrathyroid extension | No | 88 | 48 | 40 | 0.174 |
Yes | 182 | 115 | 67 | ||
Lymphovascular invasion | No | 63 | 31 | 32 | 0.039∗ |
Yes | 207 | 132 | 75 | ||
Lymph node metastasis | No | 116 | 58 | 58 | 0.002∗ |
Yes | 154 | 105 | 49 | ||
Central lymph node metastasis | No | 116 | 58 | 58 | 0.002∗ |
Yes | 154 | 105 | 49 | ||
Lateral lymph node metastasis | No | 222 | 122 | 100 | <0.001∗ |
Yes | 48 | 41 | 7 | ||
Locoregional recurrence | No | 233 | 139 | 94 | 0.547 |
Yes | 37 | 24 | 13 |
Table 3.
Multivariate analysis of the relationship between SIRT1 staining and clinicopathologic factors
Factors | Exp (β) | SE | 95.0% CI | p value |
---|---|---|---|---|
Lymphovascular invasion | 0.645 | 0.309 | (0.352, 1.182) | 0.156 |
Lateral lymph node metastasis | 0.233 | 0.443 | (0.097. 0.555) | 0.001∗ |
Central lymph node metastasis | 0.681 | 0.275 | (0.345, 0.849) | 0.162 |
Table 4.
Relationships between intensity of sirtuin 3 (SIRT3) staining and clinicopathological factors in 270 patients
Variables | No. of patients | SIRT3 | |||
---|---|---|---|---|---|
Low (Grade 1 and 2) | High (Grade 3 and 4) | p value | |||
Age, years | <45 | 104 | 52 | 52 | 0.175 |
≥45 | 166 | 69 | 97 | ||
Gender | Male | 47 | 27 | 20 | 0.055 |
Female | 223 | 94 | 129 | ||
Tumor size | ≤1 cm | 110 | 54 | 56 | 0.241 |
>1 cm | 160 | 67 | 93 | ||
Multicentricity | No | 158 | 66 | 92 | 0.232 |
Yes | 112 | 55 | 57 | ||
Microscopic capsular invasion | No | 71 | 34 | 37 | 0.544 |
Yes | 199 | 87 | 112 | ||
Extrathryoid extension | No | 88 | 43 | 45 | 0.352 |
Yes | 182 | 78 | 104 | ||
Lymphovascular invasion | No | 63 | 26 | 37 | 0.518 |
Yes | 207 | 95 | 112 | ||
Lymph node metastasis | No | 116 | 48 | 68 | 0.325 |
Yes | 154 | 73 | 81 | ||
Central lymph node metastasis | No | 116 | 48 | 68 | 0.325 |
Yes | 154 | 73 | 81 | ||
Lateral lymph node metastasis | No | 222 | 95 | 127 | 0.151 |
Yes | 48 | 26 | 22 | ||
Locoregional recurrence | No | 233 | 111 | 122 | 0.019∗ |
Yes | 37 | 10 | 27 |
Table 5.
Relationships between patterns of sirtuin staining intensity and clinicopathological factors
Variables | SIRT1 low SIRT3 low (n=88) | SIRT1 low SIRT3 high (n=75) | SIRT1 high SIRT3 low (n=33) | SIRT1 high SIRT3 high (n=74) | p value | |
---|---|---|---|---|---|---|
Age, years | <45 | 40 | 26 | 12 | 26 | 0.444 |
≥45 | 48 | 49 | 21 | 48 | ||
Gender | Male | 12 | 14 | 11 | 10 | 0.368 |
Female | 76 | 43 | 40 | 64 | ||
Tumor size | ≤1 cm | 35 | 26 | 19 | 30 | 0.168 |
>1 cm | 53 | 49 | 14 | 44 | ||
Multicentricity | No | 49 | 47 | 17 | 45 | 0.648 |
Yes | 39 | 28 | 16 | 29 | ||
Microscopic capsular invasion | No | 23 | 14 | 11 | 23 | 0.265 |
Yes | 65 | 61 | 22 | 51 | ||
Extrathryoid extension | No | 28 | 20 | 15 | 25 | 0.289 |
Yes | 60 | 55 | 18 | 49 | ||
Lymphovascular invasion | No | 17 | 14 | 9 | 23 | 0.214 |
Yes | 71 | 61 | 24 | 51 | ||
Lymph node metastasis | No | 30 | 28 | 18 | 40 | 0.025∗ |
Yes | 58 | 47 | 15 | 34 | ||
Central lymph node metastasis | No | 30 | 28 | 18 | 40 | 0.025∗ |
Yes | 58 | 47 | 15 | 34 | ||
Lateral lymph node metastasis | No | 64 | 58 | 31 | 69 | 0.001∗ |
Yes | 24 | 17 | 2 | 5 | ||
Locoregional recurrence | No | 79 | 60 | 32 | 62 | 0.072 |
Yes | 9 | 15 | 1 | 12 |