Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. KLF5 Expression in Normal Thyroid and PTC Tissues
2.2. KLF5 Functions Upstream of HIF-1α.
2.3. Downregulation of KLF5 Inhibits Tumor Cell Invasion, Migration, and Angiogenesis
2.4. Downregulation of KLF5 Inhibits PTC Cell Growth In Vitro
2.5. Inhibition of KLF5 Decreases the Self-Renewal Ability of Spheroids Generated from PTC Cells
2.6. Downregulation of KLF5 Inhibits PTC Cell Growth In Vivo
3. Discussion
4. Materials and Methods
4.1. Sample Selection
4.2. Tissue Microarray Construction and Immunohistochemistry
4.3. Cell Culture
4.4. Reagents and Antibodies
4.5. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) Assays
4.6. Gene Silencing Using siRNA
4.7. Plasmid and Transfection
4.8. Cell Invasion and Migration Assays
4.9. Sphere Forming Assay
4.10. The ALDH Activity
4.11. Chromatin Immunoprecipitation (ChIP) Assay
4.12. Animals and Xenografts Study
4.13. Statistical Analysis
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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Clinico-Pathological Characteristics | Total | KLF5 Over-Expression | KLF5 Low Expression | p-Value | |||
---|---|---|---|---|---|---|---|
No. | % | No. | % | No. | % | ||
No. of patients | 1219 | 793 | 65.1 | 426 | 34.9 | ||
Age (Y) | |||||||
<45 | 774 | 64.1 | 490 | 63.3 | 284 | 36.7 | 0.0858 |
≥45 | 434 | 35.9 | 296 | 68.2 | 138 | 31.8 | |
Sex | |||||||
Female | 916 | 75.9 | 587 | 64.1 | 329 | 35.9 | 0.2151 |
Male | 291 | 24.1 | 198 | 68.0 | 93 | 32.0 | |
Histology Type | |||||||
Classical Variant | 839 | 73.9 | 554 | 66.0 | 285 | 34.0 | <0.0001 |
Follicular Variant | 191 | 16.8 | 102 | 53.4 | 89 | 46.6 | |
Tall-Cell Variant | 105 | 9.3 | 83 | 79.0 | 22 | 21.0 | |
Extrathyroidal extension | |||||||
Absent | 523 | 49.4 | 314 | 60.0 | 209 | 40.0 | 0.0003 |
Present | 536 | 50.6 | 379 | 70.7 | 157 | 29.3 | |
pT | |||||||
pT1 | 307 | 26.1 | 186 | 60.6 | 118 | 39.4 | 0.1009 |
pT2 | 239 | 20.3 | 152 | 63.6 | 87 | 36.4 | |
pT3 | 482 | 41.0 | 330 | 68.5 | 152 | 31.5 | |
pT4 | 148 | 12.6 | 104 | 70.3 | 44 | 29.7 | |
pN | |||||||
pN0 | 553 | 46.8 | 313 | 56.6 | 240 | 43.4 | <0.0001 |
pN1 | 628 | 53.2 | 453 | 72.1 | 175 | 27.9 | |
pM | |||||||
pM0 | 1149 | 95.5 | 747 | 65.0 | 402 | 35.0 | 0.8026 |
pM1 | 54 | 4.5 | 36 | 66.7 | 16 | 33.3 | |
Stage | |||||||
I | 811 | 68.9 | 511 | 63.0 | 300 | 37.0 | 0.0003 |
II | 94 | 8.0 | 54 | 57.4 | 40 | 42.6 | |
III | 122 | 10.3 | 78 | 69.6 | 44 | 30.4 | |
IVA | 114 | 9.7 | 95 | 83.3 | 19 | 16.7 | |
IVB | 36 | 3.1 | 25 | 69.4 | 11 | 30.6 | |
HIF-1α IHC | |||||||
High | 796 | 68.7 | 530 | 66.6 | 266 | 33.4 | 0.0492 |
Low | 363 | 31.3 | 220 | 60.6 | 143 | 39.4 | |
pAKT IHC | |||||||
High | 260 | 21.7 | 185 | 71.2 | 75 | 28.8 | 0.0279 |
Low | 940 | 78.3 | 600 | 53.8 | 340 | 36.2 | |
BRAF (V600E) mutation | |||||||
Present | 498 | 59.5 | 368 | 73.9 | 130 | 26.1 | <0.0001 |
Absent | 339 | 40.5 | 184 | 54.3 | 155 | 45.7 | |
NRAS mutation | |||||||
Present | 43 | 5.1 | 20 | 46.5 | 23 | 53.5 | 0.0073 |
Absent | 794 | 94.9 | 532 | 67.0 | 262 | 33.0 | |
HRAS mutation | |||||||
Present | 24 | 2.9 | 16 | 66.7 | 8 | 33.3 | 0.9400 |
Absent | 813 | 97.1 | 536 | 65.9 | 277 | 34.1 | |
Disease Free Survival | |||||||
5 years | 72.3 | 80.4 | 0.0066 |
Clinicopathological Characteristics | n (%) |
---|---|
Age | |
Median | 38.0 |
Range (IQR) ^ | 29.0–51.0 |
Gender | |
Female | 925 (75.9) |
Male | 294 (24.1) |
Histopathology | |
Classical Variant | 839 (68.8) |
Follicular Variant | 191 (15.7) |
Tall Cell Variant | 105 (8.6) |
Other Variants | 84 (6.9) |
Extra Thyroidal Extension | |
Absent | 523 (42.9) |
Present | 536 (44.0) |
Unknown | 160 (13.1) |
pT | |
T1 | 307 (25.2) |
T2 | 239 (19.6) |
T3 | 482 (39.6) |
T4 | 148 (12.1) |
Unknown | 43 (3.5) |
pN | |
N0 | 553 (45.4) |
N1 | 628 (51.5) |
Unknown | 38 (3.1) |
pM | |
M0 | 1149 (94.3) |
M1 | 54 (4.4) |
Unknown | 16 (1.3) |
Stage | |
I | 811 (66.5) |
II | 94 (7.8) |
III | 122 (10.0) |
IVA | 114 (9.4) |
IVB | 36 (2.9) |
Unknown | 42 (3.4) |
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Pratheeshkumar, P.; Siraj, A.K.; Divya, S.P.; Parvathareddy, S.K.; Siraj, S.; Diaz, R.; Begum, R.; Al-Sobhi, S.S.; Al-Dayel, F.; Al-Kuraya, K.S. Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer. Cancers 2021, 13, 185. https://doi.org/10.3390/cancers13020185
Pratheeshkumar P, Siraj AK, Divya SP, Parvathareddy SK, Siraj S, Diaz R, Begum R, Al-Sobhi SS, Al-Dayel F, Al-Kuraya KS. Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer. Cancers. 2021; 13(2):185. https://doi.org/10.3390/cancers13020185
Chicago/Turabian StylePratheeshkumar, Poyil, Abdul K. Siraj, Sasidharan Padmaja Divya, Sandeep Kumar Parvathareddy, Sarah Siraj, Roxanne Diaz, Rafia Begum, Saif S. Al-Sobhi, Fouad Al-Dayel, and Khawla S. Al-Kuraya. 2021. "Prognostic Value and Function of KLF5 in Papillary Thyroid Cancer" Cancers 13, no. 2: 185. https://doi.org/10.3390/cancers13020185