Association of High Serum Leptin Level with Papillary Thyroid Carcinoma: A Case-Control Study
,
Abstract
Background: Recently, the prevalence of thyroid cancer has increased. Although there are known risk factors for thyroid cancer, none of them can justify this recent increase. In addition to the known risk factors, other risk factors have been proposed. Leptin can be considered as one of these risk factors due to the recent increase in the prevalence of obesity in the population. Leptin is a common factor in obesity and thyroid cancer. Leptin exerts anti-apoptotic and mitogenic effects on cancer cells and also acts as an angiogenic factor. This study aimed to evaluate the serum leptin level in individuals who suffer from papillary thyroid carcinoma (PTC), cases with benign thyroid nodules (BTN), and a healthy group.
Materials and Methods: In this study, newly diagnosed patients with PTC, BTNs, as well as euthyroid healthy control subjects without nodules were included. In all these participants, various clinical and laboratory parameters including thyroid function tests and serum leptin levels were measured and compared between the three study groups. For patients with PTC, leptin was assessed 12 weeks after total thyroidectomy.
Results: Ninety-one cases with PTC, 90 cases with BTNs, and 88 controls were recruited. Serum leptin levels in the PTC group, benign group, and the control group were 22.34, 17.60, and 13.83 ng/ml, respectively, which was considerably higher in PTC cases compared to those with benign nodules and control group (P<0.001). There was a significant association between leptin with BMI, tumor size, and tumor stage in PTC patients. Also, in patients with BTNs, a correlation between BMI, tumor size, and leptin was observed.
Conclusion: Serum leptin levels were considerably higher in cases with PTC than those with BTNs and controls and can be considered as a potential tumor marker for papillary thyroid cancer.
REFERENCES
1. Vaccarella S, Franceschi S, Bray F, et al. Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis. N Engl J Med. 2016;375(7):614-7.
2. Colonna M, Uhry Z, Guizard AV, et al. Recent trends in incidence, geographical distribution, and survival of papillary thyroid cancer in France. Cancer Epidemiol. 2015;39(4):511-8.
3. Kent WD, Hall SF, Isotalo PA, et al. Increased incidence of differentiated thyroid carcinoma and detection of subclinical disease. CMAJ. 2007;177(11):1357-61.
4. Dom G, Tarabichi M, Unger K, et al. A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas. Br J Cancer. 2012;107(6):994-1000.
5. Meinhold CL, Ron E, Schonfeld SJ, et al. Nonradiation risk factors for thyroid cancer in the US Radiologic Technologists Study. Am J Epidemiol. 2010;171(2):242-52.
6. Zhao ZG, Guo XG, Ba CX, et al. Overweight, obesity and thyroid cancer risk: a meta-analysis of cohort studies. J Int Med Res. 2012;40(6):2041-50.
7. Heidari Z, Abdani M, Mansournia MA. Insulin Resistance Associated With Differentiated Thyroid Carcinoma: Penalized Conditional Logistic Regression Analysis of a Matched Case-Control Study Data. Int J Endocrinol Metab. 2018;16(1):e14545.
8. Biondi B, Arpaia D, Montuori P, et al. Under the shadow of vesuvius: a risk for thyroid cancer? Thyroid. 2012;22(12):1296-7.
9. Jung SK, Kim K, Tae K, et al. The effect of raw vegetable and fruit intake on thyroid cancer risk among women: a case-control study in South Korea. Br J Nutr. 2013;109(1):118-28.
10. Bessesen DH. Update on obesity. J Clin Endocrinol Metab. 2008;93(6):2027-34.
11. Kim HJ, Kim NK, Choi JH, et al. Associations between body mass index and clinico-pathological characteristics of papillary thyroid cancer. Clin Endocrinol (Oxf). 2013;78(1):134-40.
12. Almquist M, Johansen D, Bjorge T, et al. Metabolic factors and risk of thyroid cancer in the Metabolic syndrome and Cancer project (Me-Can). Cancer Causes Control. 2011;22(5):743-51.
13. Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569-78.
14. Ray A, Cleary MP. The potential role of leptin in tumor invasion and metastasis. Cytokine Growth Factor Rev. 2017;38:80-97.
15. Lin TC, Huang KW, Liu CW, et al. Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression. Oncotarget. 2018;9(24):17210-9.
16. Margetic S, Gazzola C, Pegg GG, et al. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord. 2002;26(11):1407-33.
17. Dutta D, Ghosh S, Pandit K, et al. Leptin and cancer: Pathogenesis and modulation. Indian J Endocrinol Metab. 2012;16(Suppl 3):S596-600.
18. Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol. 2006;207(1):12-22.
19. Ribatti D, Belloni AS, Nico B, et al. Leptin-leptin receptor are involved in angiogenesis in human hepatocellular carcinoma. Peptides. 2008;29(9):1596-602.
20. Liu H, Wan D, Pan Z, et al. Expression and biological significance of leptin, leptin receptor, VEGF, and CD34 in colorectal carcinoma. Cell Biochem Biophys. 2011;60(3):241-4.
21. Uddin S, Bu R, Ahmed M, et al. Overexpression of leptin receptor predicts an unfavorable outcome in Middle Eastern ovarian cancer. Mol Cancer. 2009;8:74.
22. Hoon Kim J, Lee SY, Myung SC, et al. Clinical significance of the leptin and leptin receptor expressions in prostate tissues. Asian J Androl. 2008;10(6):923-8.
23. Wu MH, Chou YC, Chou WY, et al. Circulating levels of leptin, adiposity and breast cancer risk. Br J Cancer. 2009;100(4):578-82.
24. Riolfi M, Ferla R, Del Valle L, et al. Leptin and its receptor are overexpressed in brain tumors and correlate with the degree of malignancy. Brain Pathol. 2010;20(2):481-9.
25. Hollenberg AN. The role of the thyrotropin-releasing hormone (TRH) neuron as a metabolic sensor. Thyroid. 2008;18(2):131-9.
26. Menendez C, Baldelli R, Camina JP, et al. TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol. 2003;176(1):7-12.
27. La Cava A. Leptin in inflammation and autoimmunity. Cytokine. 2017;98:51-8.
28. Mathias LS, Rodrigues BM, Goncalves BM, et al. Triiodothyronine activated extranuclear pathways upregulate adiponectin and leptin in murine adipocytes. Mol Cell Endocrinol. 2020;503:110690.
29. Feldt-Rasmussen U. Thyroid and leptin. Thyroid. 2007;17(5):413-9.
30. Akinci M, Kosova F, Cetin B, et al. Leptin levels in thyroid cancer. Asian J Surg. 2009;32(4):216-23.
31. Zhao J, Wen J, Wang S, et al. Association between adipokines and thyroid carcinoma: a meta-analysis of case-control studies. BMC Cancer. 2020;20(1):788.
32. Raef H, Alfadhli E, Al-Hajjaj A, et al. High rate of persistent/recurrent disease among patients with differentiated thyroid cancer in Saudi Arabia: factors affecting nonremission. Ann Saudi Med. 2008;28(4):277-81.
33. Guo S, Liu M, Wang G, et al. Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells. Biochim Biophys Acta. 2012;1825(2):207-22.
34. Altieri DC. New wirings in the survivin networks. Oncogene. 2008;27(48):6276-84.
35. Ryan BM, O'Donovan N, Duffy MJ. Survivin: a new target for anti-cancer therapy. Cancer Treat Rev. 2009;35(7):553-62.
36. Kratzsch J, Fiedler GM, Leichtle A, et al. New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid. Clin Chem. 2005;51(8):1480-6.
37. Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017;27(11):1341-6.
38. Hedayati M, Yaghmaei P, Pooyamanesh Z, et al. Leptin: a correlated Peptide to papillary thyroid carcinoma? J Thyroid Res. 2011;2011:832163.
39. Cheng SP, Chi CW, Tzen CY, et al. Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma. Surgery. 2010;147(6):847-53.
40. Uddin S, Bavi P, Siraj AK, et al. Leptin-R and its association with PI3K/AKT signaling pathway in papillary thyroid carcinoma. Endocr Relat Cancer. 2010;17(1):191-202.
41. Warakomski J, Romuk E, Jarzab B, et al. Concentrations of Selected Adipokines, Interleukin-6, and Vitamin D in Patients with Papillary Thyroid Carcinoma in Respect to Thyroid Cancer Stages. Int J Endocrinol. 2018;2018:4921803.
42. Pellegriti G, De Vathaire F, Scollo C, et al. Papillary thyroid cancer incidence in the volcanic area of Sicily. J Natl Cancer Inst. 2009;101(22):1575-83.
43. Clero E, Doyon F, Chungue V, et al. Dietary patterns, goitrogenic food, and thyroid cancer: a case-control study in French Polynesia. Nutr Cancer. 2012;64(7):929-36.
44. Dal Maso L, Lise M, Zambon P, et al. Incidence of thyroid cancer in Italy, 1991-2005: time trends and age-period-cohort effects. Ann Oncol. 2011;22(4):957-63.
45. Friedman JM. A tale of two hormones. Nat Med. 2010;16(10):1100-6.
46. Aparicio T, Kotelevets L, Tsocas A, et al. Leptin stimulates the proliferation of human colon cancer cells in vitro but does not promote the growth of colon cancer xenografts in nude mice or intestinal tumorigenesis in Apc(Min/+) mice. Gut. 2005;54(8):1136-45.
47. Cirillo D, Rachiglio AM, la Montagna R, et al. Leptin signaling in breast cancer: an overview. J Cell Biochem. 2008;105(4):956-64.
48. Babaei A, Zarkesh-Esfahani SH, Bahrami E, et al. Restricted leptin antagonism as a therapeutic approach to treatment of autoimmune diseases. Hormones (Athens). 2011;10(1):16-26.
49. Ogunwobi OO, Beales IL. The anti-apoptotic and growth stimulatory actions of leptin in human colon cancer cells involves activation of JNK mitogen activated protein kinase, JAK2 and PI3 kinase/Akt. Int J Colorectal Dis. 2007;22(4):401-9.
50. Cheng SP, Yin PH, Chang YC, et al. Differential roles of leptin in regulating cell migration in thyroid cancer cells. Oncol Rep. 2010;23(6):1721-7.
51. Botella-Carretero JI, Alvarez-Blasco F, Sancho J, et al. Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal. Thyroid. 2006;16(4):397-402.
52. Heidari Z, Mashhadi MA, Nosratzehi S. Insulin Resistance in Patients with Benign Thyroid Nodules. Arch Iran Med. 2015;18(9):572-6.
53. Seven R. Thyroid status and leptin in Basedow-Graves and multinodular goiter patients. J Toxicol Environ Health A. 2001;63(8):575-81.
1. Vaccarella S, Franceschi S, Bray F, et al. Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis. N Engl J Med. 2016;375(7):614-7.
2. Colonna M, Uhry Z, Guizard AV, et al. Recent trends in incidence, geographical distribution, and survival of papillary thyroid cancer in France. Cancer Epidemiol. 2015;39(4):511-8.
3. Kent WD, Hall SF, Isotalo PA, et al. Increased incidence of differentiated thyroid carcinoma and detection of subclinical disease. CMAJ. 2007;177(11):1357-61.
4. Dom G, Tarabichi M, Unger K, et al. A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas. Br J Cancer. 2012;107(6):994-1000.
5. Meinhold CL, Ron E, Schonfeld SJ, et al. Nonradiation risk factors for thyroid cancer in the US Radiologic Technologists Study. Am J Epidemiol. 2010;171(2):242-52.
6. Zhao ZG, Guo XG, Ba CX, et al. Overweight, obesity and thyroid cancer risk: a meta-analysis of cohort studies. J Int Med Res. 2012;40(6):2041-50.
7. Heidari Z, Abdani M, Mansournia MA. Insulin Resistance Associated With Differentiated Thyroid Carcinoma: Penalized Conditional Logistic Regression Analysis of a Matched Case-Control Study Data. Int J Endocrinol Metab. 2018;16(1):e14545.
8. Biondi B, Arpaia D, Montuori P, et al. Under the shadow of vesuvius: a risk for thyroid cancer? Thyroid. 2012;22(12):1296-7.
9. Jung SK, Kim K, Tae K, et al. The effect of raw vegetable and fruit intake on thyroid cancer risk among women: a case-control study in South Korea. Br J Nutr. 2013;109(1):118-28.
10. Bessesen DH. Update on obesity. J Clin Endocrinol Metab. 2008;93(6):2027-34.
11. Kim HJ, Kim NK, Choi JH, et al. Associations between body mass index and clinico-pathological characteristics of papillary thyroid cancer. Clin Endocrinol (Oxf). 2013;78(1):134-40.
12. Almquist M, Johansen D, Bjorge T, et al. Metabolic factors and risk of thyroid cancer in the Metabolic syndrome and Cancer project (Me-Can). Cancer Causes Control. 2011;22(5):743-51.
13. Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569-78.
14. Ray A, Cleary MP. The potential role of leptin in tumor invasion and metastasis. Cytokine Growth Factor Rev. 2017;38:80-97.
15. Lin TC, Huang KW, Liu CW, et al. Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression. Oncotarget. 2018;9(24):17210-9.
16. Margetic S, Gazzola C, Pegg GG, et al. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord. 2002;26(11):1407-33.
17. Dutta D, Ghosh S, Pandit K, et al. Leptin and cancer: Pathogenesis and modulation. Indian J Endocrinol Metab. 2012;16(Suppl 3):S596-600.
18. Garofalo C, Surmacz E. Leptin and cancer. J Cell Physiol. 2006;207(1):12-22.
19. Ribatti D, Belloni AS, Nico B, et al. Leptin-leptin receptor are involved in angiogenesis in human hepatocellular carcinoma. Peptides. 2008;29(9):1596-602.
20. Liu H, Wan D, Pan Z, et al. Expression and biological significance of leptin, leptin receptor, VEGF, and CD34 in colorectal carcinoma. Cell Biochem Biophys. 2011;60(3):241-4.
21. Uddin S, Bu R, Ahmed M, et al. Overexpression of leptin receptor predicts an unfavorable outcome in Middle Eastern ovarian cancer. Mol Cancer. 2009;8:74.
22. Hoon Kim J, Lee SY, Myung SC, et al. Clinical significance of the leptin and leptin receptor expressions in prostate tissues. Asian J Androl. 2008;10(6):923-8.
23. Wu MH, Chou YC, Chou WY, et al. Circulating levels of leptin, adiposity and breast cancer risk. Br J Cancer. 2009;100(4):578-82.
24. Riolfi M, Ferla R, Del Valle L, et al. Leptin and its receptor are overexpressed in brain tumors and correlate with the degree of malignancy. Brain Pathol. 2010;20(2):481-9.
25. Hollenberg AN. The role of the thyrotropin-releasing hormone (TRH) neuron as a metabolic sensor. Thyroid. 2008;18(2):131-9.
26. Menendez C, Baldelli R, Camina JP, et al. TSH stimulates leptin secretion by a direct effect on adipocytes. J Endocrinol. 2003;176(1):7-12.
27. La Cava A. Leptin in inflammation and autoimmunity. Cytokine. 2017;98:51-8.
28. Mathias LS, Rodrigues BM, Goncalves BM, et al. Triiodothyronine activated extranuclear pathways upregulate adiponectin and leptin in murine adipocytes. Mol Cell Endocrinol. 2020;503:110690.
29. Feldt-Rasmussen U. Thyroid and leptin. Thyroid. 2007;17(5):413-9.
30. Akinci M, Kosova F, Cetin B, et al. Leptin levels in thyroid cancer. Asian J Surg. 2009;32(4):216-23.
31. Zhao J, Wen J, Wang S, et al. Association between adipokines and thyroid carcinoma: a meta-analysis of case-control studies. BMC Cancer. 2020;20(1):788.
32. Raef H, Alfadhli E, Al-Hajjaj A, et al. High rate of persistent/recurrent disease among patients with differentiated thyroid cancer in Saudi Arabia: factors affecting nonremission. Ann Saudi Med. 2008;28(4):277-81.
33. Guo S, Liu M, Wang G, et al. Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells. Biochim Biophys Acta. 2012;1825(2):207-22.
34. Altieri DC. New wirings in the survivin networks. Oncogene. 2008;27(48):6276-84.
35. Ryan BM, O'Donovan N, Duffy MJ. Survivin: a new target for anti-cancer therapy. Cancer Treat Rev. 2009;35(7):553-62.
36. Kratzsch J, Fiedler GM, Leichtle A, et al. New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid. Clin Chem. 2005;51(8):1480-6.
37. Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology. Thyroid. 2017;27(11):1341-6.
38. Hedayati M, Yaghmaei P, Pooyamanesh Z, et al. Leptin: a correlated Peptide to papillary thyroid carcinoma? J Thyroid Res. 2011;2011:832163.
39. Cheng SP, Chi CW, Tzen CY, et al. Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma. Surgery. 2010;147(6):847-53.
40. Uddin S, Bavi P, Siraj AK, et al. Leptin-R and its association with PI3K/AKT signaling pathway in papillary thyroid carcinoma. Endocr Relat Cancer. 2010;17(1):191-202.
41. Warakomski J, Romuk E, Jarzab B, et al. Concentrations of Selected Adipokines, Interleukin-6, and Vitamin D in Patients with Papillary Thyroid Carcinoma in Respect to Thyroid Cancer Stages. Int J Endocrinol. 2018;2018:4921803.
42. Pellegriti G, De Vathaire F, Scollo C, et al. Papillary thyroid cancer incidence in the volcanic area of Sicily. J Natl Cancer Inst. 2009;101(22):1575-83.
43. Clero E, Doyon F, Chungue V, et al. Dietary patterns, goitrogenic food, and thyroid cancer: a case-control study in French Polynesia. Nutr Cancer. 2012;64(7):929-36.
44. Dal Maso L, Lise M, Zambon P, et al. Incidence of thyroid cancer in Italy, 1991-2005: time trends and age-period-cohort effects. Ann Oncol. 2011;22(4):957-63.
45. Friedman JM. A tale of two hormones. Nat Med. 2010;16(10):1100-6.
46. Aparicio T, Kotelevets L, Tsocas A, et al. Leptin stimulates the proliferation of human colon cancer cells in vitro but does not promote the growth of colon cancer xenografts in nude mice or intestinal tumorigenesis in Apc(Min/+) mice. Gut. 2005;54(8):1136-45.
47. Cirillo D, Rachiglio AM, la Montagna R, et al. Leptin signaling in breast cancer: an overview. J Cell Biochem. 2008;105(4):956-64.
48. Babaei A, Zarkesh-Esfahani SH, Bahrami E, et al. Restricted leptin antagonism as a therapeutic approach to treatment of autoimmune diseases. Hormones (Athens). 2011;10(1):16-26.
49. Ogunwobi OO, Beales IL. The anti-apoptotic and growth stimulatory actions of leptin in human colon cancer cells involves activation of JNK mitogen activated protein kinase, JAK2 and PI3 kinase/Akt. Int J Colorectal Dis. 2007;22(4):401-9.
50. Cheng SP, Yin PH, Chang YC, et al. Differential roles of leptin in regulating cell migration in thyroid cancer cells. Oncol Rep. 2010;23(6):1721-7.
51. Botella-Carretero JI, Alvarez-Blasco F, Sancho J, et al. Effects of thyroid hormones on serum levels of adipokines as studied in patients with differentiated thyroid carcinoma during thyroxine withdrawal. Thyroid. 2006;16(4):397-402.
52. Heidari Z, Mashhadi MA, Nosratzehi S. Insulin Resistance in Patients with Benign Thyroid Nodules. Arch Iran Med. 2015;18(9):572-6.
53. Seven R. Thyroid status and leptin in Basedow-Graves and multinodular goiter patients. J Toxicol Environ Health A. 2001;63(8):575-81.
| Files | ||
| Issue | Vol 17, No 3 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v17i3.13311 | |
| Keywords | ||
| Leptin; Thyroid nodule; Thyroid Cancer, Papillary | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Refahi R, Heidari Z, Mashhadi M. Association of High Serum Leptin Level with Papillary Thyroid Carcinoma: A Case-Control Study. Int J Hematol Oncol Stem Cell Res. 2023;17(3):210-219.
