SERUM FETUIN-A AND RANKL LEVELS IN PATIENTS WITH EARLY STAGE BREAST CANCER

SERUM FETUIN-A AND RANKL LEVELS IN EARLY STAGE BREAST CANCER

  • çiğdem usul afşar M.D
  • hale aral
  • orçun can
  • didem can trablus
  • didem karaçetin
  • mehmet ali nazlı
  • Rıza umar gürsu
  • senem karabulut
Keywords: Breast cancer; fetuin-A; RANKL; serum.

Abstract


 

Purpose:Breast cancer (BC) is the primary cause of mortality due to cancer in females around the world. Fetuin-A is known to increase metastases over signals and peroxisomes related with growing. Receptor activator of nuclear factor-κB ligand (RANKL) takes part in cell adhesion, and RANKL inhibition is used in the management of cancer. We aimed to examine the relationship between serum fetuin-A, RANKL levels, other laboratory parameters and clinical findings in women diagnosed with early stage BC, in our population.

 

Methods:Women having early stage BC (n=117) met our study inclusion criteria as they had no any anti-cancer therapy before. Thirty-seven healthy women controls were also confirmed with breast examination and ultrasonography and/or mammography according to their ages. Serum samples were stored at -80°C and analysed via ELISA.

 

Results:Median age of the patients was 53 (range: 57-86) while it was 47 (range: 23-74) in the healthy group. Patients had lower high-density lipoprotein levels (p=0.002) and higher neutrophil counts (p=0.014). Fetuin-A and RANKL levels did not differ between the groups (p=0.116 and p=0.439, respectively) but RANKL leves were found to be lower in the favorable histological subtypes (p=0.04).

 

Conclusion:In this study, we found no correlation between serum fetuin-A levels and clinical findings in patients diagnosed with early stage BC. However, RANKL levels are found to be lower in subgroups with favorable histopathologic subtypes such as tubular, papillary and mucinous BC and there was statistically significant difference.

 

 

 

 

 

 

 

 

 

 

 

References

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2) Sun YS, Zhao Z, Yang ZN, Xu F, Lu HJ, Zhu ZY, et al. Risk Factors and Preventions of Breast Cancer. Int J Biol Sci 2017; 13(11): 1387-97.
3) Migowski A. Early detection of breast cancer and the interpretation of results of survival studies. Cienc Saude Coletiva 2015; 20: 1309.
4) Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol 1996; 14: 2843–77.
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6) Dabrowska AM, Tarach JS, Wojtysiak-Duma B, Duma D. Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature. Biomed Pap Med Fac Univ Palacky 2015: 159; 352-9.
7) Ochieng J, Nangami G, Sakwe A, Moye C, Alvarez J, Whalen D, et al. Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes. Int J Mol Sci 2018; 19: 2211.
8) Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA. Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation 2006; 113: 1760-7.
9) Fernández-Grijalva AL, Aguilar-Lemarroy A, Jave-Suarez LF, Gutiérrez-Ortega A, Godinez-Melgoza PA, Herrera-Rodríguez SE, et al. Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer. J Proteomics 2015; 112: 301-12.
10) Ono T, Hayashi M, Sasaki F, Nakashima T. RANKL biology: bone metabolism, the immune system, and beyond. Inflamm Regen 2020; 40: 2.
11) Donepudi MS, Kondapalli K1, Amos SJ, Venkanteshan P. Breast cancer statistics and markers. J Cancer Res Ther 2014; 10(3): 506-11.
12) Trepanowski JF, J Mey J, Varady KA. Fetuin-A: A Novel Link Between Obesity and Related Complications. Int J Obes (Lond) 2015; 39(5): 734-41.
13) Mukhopadhyay S, Mondal SA, Kumar M, Dutta D. Proinflammatory and antiinflammatory attributes of fetuin-a: a novel hepatokine modulating cardiovascular and glycemic outcomes in metabolic syndrome. Endocr Pract 2014; 20(12): 1345–51.
14) Fisher HW, Puck TT, Sato G. Molecular growth requirements of single mammalian cells: The action of fetuin in promoting cell attachment to glass. Proc Natl Acad Sci 1958; 44: 4–10.
15) Arnaud P, Miribel L, Emerson DL. α2-HS glycoprotein. Methods Enzymol 1988; 163: 431–41.
16) Mintz PJ, Rietz AC, Cardo-Vila M, Ozawa MG, Dondossola E, Do KA, et al. Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer. Proc Natl Acad Sci 2015; 112: 2515–20.
17) Gyorffy B, Surowiak P, Budczies J, Lanczky A. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS ONE 2013; 8: e82241.
18) Szasz AM, Lanczky A, Nagy A, Forster S, Hark K, Green JE, et al. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget 2016; 7: 49322–33.
19) Ochieng J, Nangami G, Sakwe A, Moye C, Alvarez J, Whalen D, et al. Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes. Int J Mol Sci 2018; 19(8): E2211.
20) Fan NJ, Kang R, Ge XY, Li M, Liu Y, Chen HM, et al. Identification α2-HS glycoprotein precursor and tubulin β-chain as serology diagnosis biomarker of colorectal cancer. Diagn Pathol 2014; 9: 53.
21) Yu CJ, Wang CL, Wang CI, Chen CD, Dan YM, Wu CC, et al. Comprehensive proteome analysis of malignant pleural effusion for lung cancer biomarker discovery by using multidimensional protein identification technology. J Proteome Res 2011; 10: 4671–82.
22) Fernández-Grijalva AL, Aguilar-Lemarroy A, Jave-Suarez LF, Gutiérrez-Ortega A, Godinez-Melgoza PA, Herrera-Rodríguez SE, et al. Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer. J Proteomics 2015; 112: 301-12.
23) Nangami GN, Watson K, Parker-Johnson K, Okereke KO, Sakwe A, Thompson P, et al. Fetuin-A (α2HS-glycoprotein) is a serum chemo-attractant that also promotes invasion of tumor cells through Matrigel. Biochem Biophys Res Commun 2013; 438(4): 660-5.
24) Infante M, Fabi A, Cognetti F, Gorini S, Caprio M, Fabbri A. RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives. J Exp Clin Cancer Res 2019; 38(1): 12.
25) Kiesel L, Kohl A. Role of the RANK/RANKL pathway in breast cancer. Maturitas 2016; 86: 10-6.












REFERENCES
1) Coleman MP, Quaresma M, Berrino F, Lutz JM, Angelis RD, Capocaccia R, et al. Cancer survival in five continents: a worldwide population-based study (CONCORD). Lancet Oncol 2008; 9(8): 730–56.
2) Sun YS, Zhao Z, Yang ZN, Xu F, Lu HJ, Zhu ZY, et al. Risk Factors and Preventions of Breast Cancer. Int J Biol Sci 2017; 13(11): 1387-97.
3) Migowski A. Early detection of breast cancer and the interpretation of results of survival studies. Cienc Saude Coletiva 2015; 20: 1309.
4) Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol 1996; 14: 2843–77.
5) Yi JK, Chang JW, Han W, Lee JW, Ko E, Kim DH, et al. Cancer Epidemiol Biomarkers Prev 2009: 18; 1357-64.
6) Dabrowska AM, Tarach JS, Wojtysiak-Duma B, Duma D. Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature. Biomed Pap Med Fac Univ Palacky 2015: 159; 352-9.
7) Ochieng J, Nangami G, Sakwe A, Moye C, Alvarez J, Whalen D, et al. Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes. Int J Mol Sci 2018; 19: 2211.
8) Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA. Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation 2006; 113: 1760-7.
9) Fernández-Grijalva AL, Aguilar-Lemarroy A, Jave-Suarez LF, Gutiérrez-Ortega A, Godinez-Melgoza PA, Herrera-Rodríguez SE, et al. Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer. J Proteomics 2015; 112: 301-12.
10) Ono T, Hayashi M, Sasaki F, Nakashima T. RANKL biology: bone metabolism, the immune system, and beyond. Inflamm Regen 2020; 40: 2.
11) Donepudi MS, Kondapalli K1, Amos SJ, Venkanteshan P. Breast cancer statistics and markers. J Cancer Res Ther 2014; 10(3): 506-11.
12) Trepanowski JF, J Mey J, Varady KA. Fetuin-A: A Novel Link Between Obesity and Related Complications. Int J Obes (Lond) 2015; 39(5): 734-41.
13) Mukhopadhyay S, Mondal SA, Kumar M, Dutta D. Proinflammatory and antiinflammatory attributes of fetuin-a: a novel hepatokine modulating cardiovascular and glycemic outcomes in metabolic syndrome. Endocr Pract 2014; 20(12): 1345–51.
14) Fisher HW, Puck TT, Sato G. Molecular growth requirements of single mammalian cells: The action of fetuin in promoting cell attachment to glass. Proc Natl Acad Sci 1958; 44: 4–10.
15) Arnaud P, Miribel L, Emerson DL. α2-HS glycoprotein. Methods Enzymol 1988; 163: 431–41.
16) Mintz PJ, Rietz AC, Cardo-Vila M, Ozawa MG, Dondossola E, Do KA, et al. Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer. Proc Natl Acad Sci 2015; 112: 2515–20.
17) Gyorffy B, Surowiak P, Budczies J, Lanczky A. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS ONE 2013; 8: e82241.
18) Szasz AM, Lanczky A, Nagy A, Forster S, Hark K, Green JE, et al. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget 2016; 7: 49322–33.
19) Ochieng J, Nangami G, Sakwe A, Moye C, Alvarez J, Whalen D, et al. Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes. Int J Mol Sci 2018; 19(8): E2211.
20) Fan NJ, Kang R, Ge XY, Li M, Liu Y, Chen HM, et al. Identification α2-HS glycoprotein precursor and tubulin β-chain as serology diagnosis biomarker of colorectal cancer. Diagn Pathol 2014; 9: 53.
21) Yu CJ, Wang CL, Wang CI, Chen CD, Dan YM, Wu CC, et al. Comprehensive proteome analysis of malignant pleural effusion for lung cancer biomarker discovery by using multidimensional protein identification technology. J Proteome Res 2011; 10: 4671–82.
22) Fernández-Grijalva AL, Aguilar-Lemarroy A, Jave-Suarez LF, Gutiérrez-Ortega A, Godinez-Melgoza PA, Herrera-Rodríguez SE, et al. Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer. J Proteomics 2015; 112: 301-12.
23) Nangami GN, Watson K, Parker-Johnson K, Okereke KO, Sakwe A, Thompson P, et al. Fetuin-A (α2HS-glycoprotein) is a serum chemo-attractant that also promotes invasion of tumor cells through Matrigel. Biochem Biophys Res Commun 2013; 438(4): 660-5.
24) Infante M, Fabi A, Cognetti F, Gorini S, Caprio M, Fabbri A. RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives. J Exp Clin Cancer Res 2019; 38(1): 12.
25) Kiesel L, Kohl A. Role of the RANK/RANKL pathway in breast cancer. Maturitas 2016; 86: 10-6.













1) Coleman MP, Quaresma M, Berrino F, Lutz JM, Angelis RD, Capocaccia R, et al. Cancer survival in five continents: a worldwide population-based study (CONCORD). Lancet Oncol 2008; 9(8): 730–56.
2) Sun YS, Zhao Z, Yang ZN, Xu F, Lu HJ, Zhu ZY, et al. Risk Factors and Preventions of Breast Cancer. Int J Biol Sci 2017; 13(11): 1387-97.
3) Migowski A. Early detection of breast cancer and the interpretation of results of survival studies. Cienc Saude Coletiva 2015; 20: 1309.
4) Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol 1996; 14: 2843–77.
5) Yi JK, Chang JW, Han W, Lee JW, Ko E, Kim DH, et al. Cancer Epidemiol Biomarkers Prev 2009: 18; 1357-64.
6) Dabrowska AM, Tarach JS, Wojtysiak-Duma B, Duma D. Fetuin-A (AHSG) and its usefulness in clinical practice. Review of the literature. Biomed Pap Med Fac Univ Palacky 2015: 159; 352-9.
7) Ochieng J, Nangami G, Sakwe A, Moye C, Alvarez J, Whalen D, et al. Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes. Int J Mol Sci 2018; 19: 2211.
8) Ix JH, Shlipak MG, Brandenburg VM, Ali S, Ketteler M, Whooley MA. Association between human fetuin-A and the metabolic syndrome: data from the Heart and Soul Study. Circulation 2006; 113: 1760-7.
9) Fernández-Grijalva AL, Aguilar-Lemarroy A, Jave-Suarez LF, Gutiérrez-Ortega A, Godinez-Melgoza PA, Herrera-Rodríguez SE, et al. Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer. J Proteomics 2015; 112: 301-12.
10) Ono T, Hayashi M, Sasaki F, Nakashima T. RANKL biology: bone metabolism, the immune system, and beyond. Inflamm Regen 2020; 40: 2.
11) Donepudi MS, Kondapalli K1, Amos SJ, Venkanteshan P. Breast cancer statistics and markers. J Cancer Res Ther 2014; 10(3): 506-11.
12) Trepanowski JF, J Mey J, Varady KA. Fetuin-A: A Novel Link Between Obesity and Related Complications. Int J Obes (Lond) 2015; 39(5): 734-41.
13) Mukhopadhyay S, Mondal SA, Kumar M, Dutta D. Proinflammatory and antiinflammatory attributes of fetuin-a: a novel hepatokine modulating cardiovascular and glycemic outcomes in metabolic syndrome. Endocr Pract 2014; 20(12): 1345–51.
14) Fisher HW, Puck TT, Sato G. Molecular growth requirements of single mammalian cells: The action of fetuin in promoting cell attachment to glass. Proc Natl Acad Sci 1958; 44: 4–10.
15) Arnaud P, Miribel L, Emerson DL. α2-HS glycoprotein. Methods Enzymol 1988; 163: 431–41.
16) Mintz PJ, Rietz AC, Cardo-Vila M, Ozawa MG, Dondossola E, Do KA, et al. Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer. Proc Natl Acad Sci 2015; 112: 2515–20.
17) Gyorffy B, Surowiak P, Budczies J, Lanczky A. Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS ONE 2013; 8: e82241.
18) Szasz AM, Lanczky A, Nagy A, Forster S, Hark K, Green JE, et al. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget 2016; 7: 49322–33.
19) Ochieng J, Nangami G, Sakwe A, Moye C, Alvarez J, Whalen D, et al. Impact of Fetuin-A (AHSG) on Tumor Progression and Type 2 Diabetes. Int J Mol Sci 2018; 19(8): E2211.
20) Fan NJ, Kang R, Ge XY, Li M, Liu Y, Chen HM, et al. Identification α2-HS glycoprotein precursor and tubulin β-chain as serology diagnosis biomarker of colorectal cancer. Diagn Pathol 2014; 9: 53.
21) Yu CJ, Wang CL, Wang CI, Chen CD, Dan YM, Wu CC, et al. Comprehensive proteome analysis of malignant pleural effusion for lung cancer biomarker discovery by using multidimensional protein identification technology. J Proteome Res 2011; 10: 4671–82.
22) Fernández-Grijalva AL, Aguilar-Lemarroy A, Jave-Suarez LF, Gutiérrez-Ortega A, Godinez-Melgoza PA, Herrera-Rodríguez SE, et al. Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer. J Proteomics 2015; 112: 301-12.
23) Nangami GN, Watson K, Parker-Johnson K, Okereke KO, Sakwe A, Thompson P, et al. Fetuin-A (α2HS-glycoprotein) is a serum chemo-attractant that also promotes invasion of tumor cells through Matrigel. Biochem Biophys Res Commun 2013; 438(4): 660-5.
24) Infante M, Fabi A, Cognetti F, Gorini S, Caprio M, Fabbri A. RANKL/RANK/OPG system beyond bone remodeling: involvement in breast cancer and clinical perspectives. J Exp Clin Cancer Res 2019; 38(1): 12.
25) Kiesel L, Kohl A. Role of the RANK/RANKL pathway in breast cancer. Maturitas 2016; 86: 10-6.
Published
2022/10/18
Section
Original paper