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Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer

  • Authors:
    • Bruna Cristina Borges
    • Pedro Augusto Do Amaral
    • Luiz Ricardo Soldi
    • Victor Luigi Costa Silva
    • Fernanda Carvalho De Souza
    • Felipe Andrés Cordeiro Da Luz
    • Rogério Agenor De Araújo
    • Marcelo José Barbosa Silva
  • View Affiliations / Copyright

    Affiliations: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG 38400‑902, Brazil, Núcleo de Prevenção, Pesquisa e Projeto de Câncer, Hospital do Câncer, Uberlândia, MG 38400‑902, Brazil
    Copyright: © Borges et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 93
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    Published online on: February 25, 2022
       https://doi.org/10.3892/mco.2022.2526
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Abstract

Klotho, a cellular anti‑senescence protein, is related to antitumor actions, growth regulation, proliferation and invasiveness in several types of tumor, including breast cancer. The present study aimed to analyze the serum levels of αKlotho in patients with breast cancer according to histopathological and immunohistochemical variables. A total of 74 patients and 60 healthy controls were recruited. Peripheral blood samples were collected and serum levels were assessed by sandwich ELISA. Clinical and diagnostic data were obtained from medical records and databases of the Clinical Hospital of the Federal University of Uberlândia (Uberlândia, Brazil). The results indicated no difference in the levels of αKlotho between patients and controls (P=0.068); however, the number of patients with breast cancer with undetectable αKlotho was high (n=52). Thus, the variables that were associated with the lowest survival rates were analyzed, relating them to undetectable αKlotho. Among cases of metastatic tumors or tumors with poor differentiation, positive lymph node status and triple‑negative status, patients with undetectable αKlotho predominated and had unfavorable overall survival. Due to the significant results obtained in triple‑negative patients, an in vitro analysis was performed to determine whether estrogen receptors (ERs) have a role in αKlotho production. Treatment of MCF‑7 cells with ER agonists, estradiol (E2) and diarylpropionitrile (DPN), resulted in increases in αKlotho expression and supernatant levels of both agonists, demonstrating a direct association between the ER and Klotho production; of note, the ERβ‑specific agonist DPN tripled αKlotho expression when compared to E2 (P=0.078). These data suggested that undetectable αKlotho in the serum of patients with breast cancer is related to unfavorable histopathological variables and poor prognosis and ERs possibly have an important role in maintaining adequate quantities of αKlotho.
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1 

Kurosu H, Yamamoto M, Clark JD, Pastor JV, Nandi A, Gurnani P, McGuinness OP, Chikuda H, Yamaguchi M, Kawaguchi H, et al: Suppression of aging in mice by the hormone Klotho. Science. 309:1829–1833. 2005.PubMed/NCBI View Article : Google Scholar

2 

Kuro-o M, Matsumara Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, et al: Mutation of the mouse Klotho gene leads to a syndrome resembling ageing. Nature. 390:45–51. 1997.PubMed/NCBI View Article : Google Scholar

3 

Nabeshima YI: Klotho: A fundamental regulator of aging. Ageing Res Rev. 1:627–638. 2002.PubMed/NCBI View Article : Google Scholar

4 

Sopjani M and Dërmaku-Sopjani M: Klotho-dependent cellular transport regulation. Vitam Horm. 101:59–84. 2016.PubMed/NCBI View Article : Google Scholar

5 

Kharitonenkov A: FGFs and metabolism. Curr Opin Pharmacol. 9:805–810. 2009.PubMed/NCBI View Article : Google Scholar

6 

Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S and Yamashita T: Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 444:770–774. 2006.PubMed/NCBI View Article : Google Scholar

7 

Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW and Kuro-o M: Regulation of fibroblast growth factor-23 signaling by Klotho. J Biol Chem. 281:6120–6123. 2006.PubMed/NCBI View Article : Google Scholar

8 

Ito S, Kinoshita S, Shiraishi N, Nakagawa S, Sekine S, Fujimori T and Nabeshima YI: Molecular cloning and expression analyses of mouse betaklotho, which encodes a novel Klotho family protein. Mech Dev. 98:115–119. 2000.PubMed/NCBI View Article : Google Scholar

9 

Ito S, Fujimori T, Hayashizaki Y and Nabeshima Y: Identification of a novel mouse membrane-bound family 1 glycosidase-like protein, which carries an atypical active site structure. Biochim Biophys Acta. 1576:341–345. 2002.PubMed/NCBI View Article : Google Scholar

10 

Kim JH, Hwang KH, Park KS, Kong ID and Cha SK: Biological role of anti-aging protein Klotho. J Lifestyle Med. 5:1–6. 2015.PubMed/NCBI View Article : Google Scholar

11 

Chen CD, Tung TV, Liang J, Zeldich E, Tucker Zhou TB, Turk BE and Abraham CR: Identification of cleavage sites leading to the shed form of the anti-aging protein Klotho. Biochemistry. 53:5579–5587. 2014.PubMed/NCBI View Article : Google Scholar

12 

Chen CD, Podvin S, Gillespie E, Leeman SE and Abraham CR: Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci USA. 104:19796–19801. 2007.PubMed/NCBI View Article : Google Scholar

13 

Bloch L, Sineshchekova O, Reichenbach D, Reiss K, Saftig P, Kuro-o M and Kaether C: Klotho is a substrate for alpha-, beta- and gamma-secretase. FEBS Lett. 583:3221–3224. 2009.PubMed/NCBI View Article : Google Scholar

14 

Akimoto T, Yoshizawa H, Watanabe Y, Numata A, Yamazaki T, Takeshima E, Iwazu K, Komada T, Otani N, Morishita Y, et al: Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease. BMC Nephrol. 13(155)2012.PubMed/NCBI View Article : Google Scholar

15 

Matsumura Y, Aizawa H, Shiraki-lida T, Nagai R, Kuro-o M and Nabeshima Y: Identification of the human Klotho gene and its two transcripts encoding membrane and secreted Klotho protein. Biochem Biophys Res Commun. 242:626–630. 1998.PubMed/NCBI View Article : Google Scholar

16 

Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, et al: Alpha-klotho as a regulator of calcium homeostasis. Science. 316:1615–1618. 2007.PubMed/NCBI View Article : Google Scholar

17 

Xuan NT and Hai N: Changes in expression of Klotho affect physiological processes, diseases, and cancer. Iran J Basic Med Sci. 21:3–8. 2018.PubMed/NCBI

18 

Zhou X and Wang X: Klotho: A novel biomarker for cancer. J Cancer Res Clin Oncol. 141:961–969. 2015.PubMed/NCBI View Article : Google Scholar

19 

Perri F, Longo F, Giuliano M, Sabbatino F, Favia G, Ionna F, Addeo R, Della Vittoria Scarpati G, Di Lorenzo G and Pisconti S: Epigenetic control of gene expression: Potential implications for cancer treatment. Crit Rev Oncol Hematol. 111:166–172. 2017.PubMed/NCBI View Article : Google Scholar

20 

Chen B, Ma X, Liu S, Zhao W and Wu J: Inhibition of lung cancer cells growth, motility and induction of apoptosis by Klotho, a novel secreted Wnt antagonist, in a dose-dependent manner. Cancer Biol Ther. 13:1221–1228. 2012.PubMed/NCBI View Article : Google Scholar

21 

Chen TJ, Ren H, Thakur A, Yang T, Li Y, Zhang S, Wang T and Chen M: Decreased level of Klotho contributes to drug resistance in lung cancer cells: Involving in Klotho-mediated cell autophagy. DNA Cell Biol. 35:751–757. 2016.PubMed/NCBI View Article : Google Scholar

22 

Wang Y, Chen L, Huang G, He D, He J, Xu W, Zou C, Zong F, Li Y, Chen B, et al: Klotho sensitizes human lung cancer cell line to cisplatin via PI3k/Akt pathway. PLoS One. 8(e57391)2013.PubMed/NCBI View Article : Google Scholar

23 

Abramovitz L, Rubinek T, Ligumsky H, Bose S, Barshack I, Avivi C, Kaufman B and Wolf I: KL1 internal repeat mediates Klotho tumor suppressor activities and inhibits bFGF and IGF-I signaling in pancreatic cancer. Clin Cancer Res. 17:4254–4266. 2011.PubMed/NCBI View Article : Google Scholar

24 

Rubinek T, Shulman M, Israeli S, Bose S, Avraham A, Zundelevich A, Evron E, Gal-Yam EN, Kaufman B and Wolf I: Epigenetic silencing of the tumor suppressor Klotho in human breast cancer. Breast Cancer Res Treat. 133:649–657. 2012.PubMed/NCBI View Article : Google Scholar

25 

Wolf I, Levanon-Cohen S, Bose S, Ligumsky H, Sredni B, Kanety H, Kuro-o M, Karlan B, Kaufman B, Koeffler HP and Rubinek T: Klotho: A tumor suppressor and a modulator of the IGF-1 and FGF pathways in human breast cancer. Oncogene. 27:7094–7105. 2008.PubMed/NCBI View Article : Google Scholar

26 

Doi S, Zou Y, Togao O, Pastor JV, John GB, Wang L, Shiizaki K, Gotschall R, Schiavi S, Yorioka N, et al: Klotho inhibits transforming growth factor-beta1 (TGF-beta1) signaling and suppresses renal fibrosis and cancer metastasis in mice. J Biol Chem. 286:8655–8665. 2011.PubMed/NCBI View Article : Google Scholar

27 

Tang X, Fan Z, Wang Y, Ji G, Wang M, Lin J and Huang S: Expression of Klotho and β-catenin in esophageal squamous cell carcinoma, and their clinicopathological and prognostic significance. Dis Esophagus. 29:207–214. 2016.PubMed/NCBI View Article : Google Scholar

28 

Tang X, Wang Y, Fan Z, Ji G, Wang M, Lin J, Huang S and Meltzer SJ: Klotho: A tumor suppressor and modulator of the Wnt/β-catenin pathway in human hepatocellular carcinoma. Lab Invest. 96:197–205. 2016.PubMed/NCBI View Article : Google Scholar

29 

Lee J, Jeong DJ, Kim J, Lee S, Park JH, Chang B, Jung SI, Yi L, Han Y, Yang Y, et al: The anti-aging gene Klotho is a novel target for epigenetic silencing in human cervical carcinoma. Mol Cancer. 9(109)2010.PubMed/NCBI View Article : Google Scholar

30 

Usuda J, Ichinose S, Ishizumi T, Ohtani K, Inoue T, Saju H, Kakihana M, Kajiwara N, Uchida O, Nomura M, et al: Klotho is a novel biomarker for good survival in resected large cell neuroendocrine carcinoma of the lung. Lung Cancer. 72:355–359. 2011.PubMed/NCBI View Article : Google Scholar

31 

Yan Y, Wang Y, Xiong Y, Lin X, Zhou P and Chen Z: Reduced Klotho expression contributes to poor survival rates in human patients with ovarian cancer, and overexpression of Klotho inhibits the progression of ovarian cancer partly via the inhibition of systemic inflammation in nude mice. Mol Med Rep. 15:1777–1785. 2017.PubMed/NCBI View Article : Google Scholar

32 

Kim JH, Hwang KH, Lkhagvadorj S, Jung JH, Chung HC, Park HS, Kong ID, Eom M and Cha SK: Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome. Korean J Physiol Pharmacol. 20:297–304. 2016.PubMed/NCBI View Article : Google Scholar

33 

Li XX, Huang LY, Peng JJ, Liang L, Shi DB, Zheng HT and Cai SJ: Klotho suppresses growth and invasion of colon cancer cells through inhibition of IGF1R-mediated PI3K/AKT pathway. Int J Oncol. 45:611–618. 2014.PubMed/NCBI View Article : Google Scholar

34 

Seo M, Kim MS, Jang A, Chung HJ, Noh Y, Kim DH, Lee J, Ko K and Myung SC: Epigenetic suppression of the anti-aging gene Klotho in human prostate cancer cell lines. Anim Cells Syst (Seoul). 21:223–232. 2017.PubMed/NCBI View Article : Google Scholar

35 

Kusaba T, Okigaki M, Matui A, Murakami M, Ishikawa K, Kimura T, Sonomura K, Adachi Y, Shibuya M, Shirayama T, et al: Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity. Proc Natl Acad Sci USA. 107:19308–19313. 2010.PubMed/NCBI View Article : Google Scholar

36 

Galkina E and Ley K: Vascular adhesion molecules in atherosclerosis. Arterioscler Thromb Vasc Biol. 27:2292–2301. 2007.PubMed/NCBI View Article : Google Scholar

37 

Maekawa Y, Ishikawa K, Yasuda O, Oguro R, Hanasaki H, Kida I, Takemura Y, Ohishi M, Katsuya T and Rakugi H: Klotho suppresses TNF-alpha-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation. Endocrine. 35:341–346. 2009.PubMed/NCBI View Article : Google Scholar

38 

Xie B, Zhou J, Shu G, Liu DC, Zhou J, Chen J and Yuan L: Restoration of Klotho gene expression induces apoptosis and autophagy in gastric cancer cells: Tumor suppressive role of Klotho in gastric cancer. Cancer Cell Int. 13(18)2013.PubMed/NCBI View Article : Google Scholar

39 

Shu G, Xie B, Ren F, Liu DC and Zhou J, Li Q, Chen J, Yuan L and Zhou J: Restoration of Klotho expression induces apoptosis and autophagy in hepatocellular carcinoma cells. Cell Oncol (Dordr). 36:121–129. 2013.PubMed/NCBI View Article : Google Scholar

40 

Dalton GD, Xie J, An SW and Huang CL: New insights into the mechanism of action of soluble Klotho. Front Endocrinol (Lausanne). 8(323)2017.PubMed/NCBI View Article : Google Scholar

41 

Mencke R, Olauson H and Hillebrands JL: Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and therapeutic strategies. Adv Drug Deliv Rev. 121:85–100. 2017.PubMed/NCBI View Article : Google Scholar

42 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018.PubMed/NCBI View Article : Google Scholar

43 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015.PubMed/NCBI View Article : Google Scholar

44 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. 2020.PubMed/NCBI View Article : Google Scholar

45 

Malhotra GK, Zhao X, Band H and Band V: Histological, molecular and functional subtypes of breast cancers. Cancer Biol Ther. 10:955–960. 2010.PubMed/NCBI View Article : Google Scholar

46 

Harbeck N, Thomssen C and Gnant M: St. Gallen 2013: Brief preliminary summary of the consensus discussion. Breast Care (Basel). 8:102–109. 2013.PubMed/NCBI View Article : Google Scholar

47 

Akaza H: TNM classification. Nihon Hinyokika Gakkai Zasshi. 85:229–241. 1994.PubMed/NCBI View Article : Google Scholar : (In Japanese).

48 

Brown RB and Razzaque MS: Phosphate toxicity and tumorigenesis. Biochim Biophys Acta Rev Cancer. 1869:303–309. 2018.PubMed/NCBI View Article : Google Scholar

49 

Ligumsky H, Rubinek T, Merenbakh-Lamin K, Yeheskel A, Sertchook R, Shahmoon S, Aviel-Ronen S and Wolf I: Tumor suppressor activity of Klotho in breast cancer is revealed by structure-function analysis. Mol Cancer Res. 13:1398–1407. 2015.PubMed/NCBI View Article : Google Scholar

50 

Trošt N, Peña-Llopis S, Koirala S, Stojan J, Potts PR, Fon Tacer K and Martinez ED: γKlotho is a novel marker and cell survival factor in a subset of triple negative breast cancers. Oncotarget. 7:2611–2628. 2016.PubMed/NCBI View Article : Google Scholar

51 

Untch M, Gerber B, Harbeck N, Jackisch C, Marschner N, Möbus V, von Minckwitz G, Loibl S, Beckmann MW, Blohmer JU, et al: 13th st. Gallen international breast cancer conference 2013: primary therapy of early breast cancer evidence, controversies, consensus-opinion of a german team of experts (Zurich 2013). Breast Care (Basel). 8:221–229. 2013.PubMed/NCBI View Article : Google Scholar

52 

Dembinski TC, Leung CK and Shiu RP: Evidence for a novel pituitary factor that potentiates the mitogenic effect of estrogen in human breast cancer cells. Cancer Res. 45:3083–3089. 1985.PubMed/NCBI

53 

U.S National Library of Medicine (NIH): BLAST®: Basic local alignment search tool. National Center for Biotechnology Information, Bethesda, MD, 2021.

54 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

55 

Ragab HM, Samy N, Afify M, El Maksoud NA and Shaaban HM: Assessment of Ki-67 as a potential biomarker in patients with breast cancer. J Genet Eng Biotechnol. 16:479–484. 2018.PubMed/NCBI View Article : Google Scholar

56 

Park S, Park S, Kim J, Ahn S, Park KH and Lee H: Assessment of Ki-67 for predicting effective prognosis in breast cancer subtypes. Biomed Sci Lett. 24:9–14. 2018.

57 

Colomer R, Aranda-López I, Albanell J, García-Caballero T, Ciruelos E, López-García MÁ, Cortés J, Rojo F, Martín M and Palacios-Calvo J: Biomarkers in breast cancer: A consensus statement by the Spanish society of medical oncology and the Spanish society of pathology. Clin Transl Oncol. 20:815–826. 2018.PubMed/NCBI View Article : Google Scholar

58 

Kuro-o M: Klotho and aging. Biochim Biophys Acta. 1790:1049–1058. 2009.PubMed/NCBI View Article : Google Scholar

59 

Kuro-o M: Klotho in health and disease. Curr Opin Nephrol Hypertens. 21:362–368. 2012.PubMed/NCBI View Article : Google Scholar

60 

Arbel Rubinstein T, Shahmoon S, Zigmond E, Etan T, Merenbakh-Lamin K, Pasmanik-Chor M, Har-Zahav G, Barshack I, Vainer GW, Skalka N, et al: Klotho suppresses colorectal cancer through modulation of the unfolded protein response. Oncogene. 38:794–807. 2019.PubMed/NCBI View Article : Google Scholar

61 

Chang B, Kim J, Jeong D, Jeong Y, Jeon S, Jung SI, Yang Y, Kim KI, Lim JS, Kim C and Lee MS: Klotho inhibits the capacity of cell migration and invasion in cervical cancer. Oncol Rep. 28:1022–1028. 2012.PubMed/NCBI View Article : Google Scholar

62 

Sopjani M, Rinnerthaler M, Kruja J and Dermaku-Sopjani M: Intracellular Signaling of the aging suppressor protein Klotho. Curr Mol Med. 15:27–37. 2015.PubMed/NCBI View Article : Google Scholar

63 

Pako J, Bikov A, Barta I, Matsueda H, Puskas R, Galffy G, Kerpel-Fronius A, Antus B and Horvath I: Assessment of the circulating Klotho protein in lung cancer patients. Pathol Oncol Res. 26:233–238. 2020.PubMed/NCBI View Article : Google Scholar

64 

Oh HJ, Oh H, Nam BY, You JS, Ryu DR, Kang SW and Chung YE: The protective effect of Klotho against contrast-associated acute kidney injury via the antioxidative effect. Am J Physiol Renal Physiol. 317:F881–F889. 2019.PubMed/NCBI View Article : Google Scholar

65 

Brominska B, Gabryel P, Jarmolowska-Jurczyszyn D, Janicka-Jedyńska M, Kluk A, Trojanowski T, Brajer-Luftmann B, Woliński K, Czepczyński R, Gut P, et al: Klotho expression and nodal involvement as predictive factors for large cell lung carcinoma. Arch Med Sci. 15:1010–1016. 2019.PubMed/NCBI View Article : Google Scholar

66 

Soliman NA and Yussif SM: Ki-67 as a prognostic marker according to breast cancer molecular subtype. Cancer Biol Med. 13:496–504. 2016.PubMed/NCBI View Article : Google Scholar

67 

Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M and Ortmann O: Ki-67 is a prognostic parameter in breast cancer patients: Results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 139:539–552. 2013.PubMed/NCBI View Article : Google Scholar

68 

Wu Q, Ma Q, Deng Y, Luo W, Zhao Y, Li W and Zhou Q: Prognostic value of ki-67 in patients with resected triple-negative breast cancer: A meta-analysis. Front Oncol. 9(1068)2019.PubMed/NCBI View Article : Google Scholar

69 

Bruey JM, Kantarjian H, Estrov Z, Zhang Z, Ma W, Albitar F, Abdool A, Thomas D, Yeh C, O'Brien S and Albitar M: Circulating Ki-67 protein in plasma as a biomarker and prognostic indicator of acute lymphoblastic leukemia. Leuk Res. 34:173–176. 2010.PubMed/NCBI View Article : Google Scholar

70 

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B and Senn HJ: Panel members. Strategies for subtypes-dealing with the diversity of breast cancer: Highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol. 22:1736–1747. 2011.PubMed/NCBI View Article : Google Scholar

71 

Varga Z, Diebold J, Dommann-Scherrer C, Frick H, Kaup D, Noske A, Obermann E, Ohlschlegel C, Padberg B, Rakozy C, et al: How reliable is Ki-67 immunohistochemistry in grade 2 breast carcinomas? A QA study of the Swiss working group of breast- and gynecopathologists. PLoS One. 7(e37379)2012.PubMed/NCBI View Article : Google Scholar

72 

Polley MY, Leung SC, McShane LM, Gao D, Hugh JC, Mastropasqua MG, Viale G, Zabaglo LA, Penault-Llorca F, Bartlett JM, et al: An international ki67 reproducibility study. J Natl Cancer Inst. 105:1897–1906. 2013.PubMed/NCBI View Article : Google Scholar

73 

Jonat W and Arnold N: Is the Ki-67 labelling index ready for clinical use? Ann Oncol. 22:500–502. 2011.PubMed/NCBI View Article : Google Scholar

74 

Gudlaugsson E, Skaland I, Janssen EA, Smaaland R, Shao Z, Malpica A, Voorhorst F and Baak JP: Comparison of the effect of different techniques for measurement of Ki67 proliferation on reproducibility and prognosis prediction accuracy in breast cancer. Histopathology. 61:1134–1144. 2012.PubMed/NCBI View Article : Google Scholar

75 

Mikami Y, Ueno T, Yoshimura K, Tsuda H, Kurosumi M, Masuda S, Horii R, Toi M and Sasano H: Interobserver concordance of Ki67 labeling index in breast cancer: Japan breast cancer research group Ki67 ring study. Cancer Sci. 104:1539–1543. 2013.PubMed/NCBI View Article : Google Scholar

76 

Christopoulos PF, Msaouel P and Koutsilieris M: The role of the insulin-like growth factor-1 system in breast cancer. Mol Cancer. 14(43)2015.PubMed/NCBI View Article : Google Scholar

77 

Oloomi M, Moazzezy N and Bouzari S: Comparing blood versus tissue-based biomarkers expression in breast cancer patients. Heliyon. 6(e03728)2020.PubMed/NCBI View Article : Google Scholar

78 

Diniz RW, Guerra MR, Cintra JR, Fayer VA and Teixeira MT: Disease-free survival in patients with non-metastatic breast cancer. Rev Assoc Med Bras (1992). 62:407–413. 2016.PubMed/NCBI View Article : Google Scholar

79 

Li X, Yang J, Peng L, Sahin AA, Huo L, Ward KC, O'Regan R, Torres MA and Meisel JL: Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. 161:279–287. 2017.PubMed/NCBI View Article : Google Scholar

80 

Carter CL, Allen C and Henson DE: Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 63:181–187. 1989.PubMed/NCBI View Article : Google Scholar

81 

Dai X, Li Y, Bai Z and Tang XQ: Molecular portraits revealing the heterogeneity of breast tumor subtypes defined using immunohistochemistry markers. Sci Rep. 5(14499)2015.PubMed/NCBI View Article : Google Scholar

82 

Usuda J, Ichinose S, Ishizumi T, Ohtani K, Inoue T, Saji H, Kakihana M, Kajiwara N, Uchida O, Nomura M, et al: Klotho predicts good clinical outcome in patients with limited-disease small cell lung cancer who received surgery. Lung Cancer. 74:332–337. 2011.PubMed/NCBI View Article : Google Scholar

83 

Zhang J, Chen X, Shen L, Wang X, Wang L, Sun X and Qu S: The association between lymph node stage and clinical prognosis in thyroid cancer. Front Endocrinol (Lausanne). 11(90)2020.PubMed/NCBI View Article : Google Scholar

84 

Nottegar A, Veronese N, Senthil M, Roumen RM, Stubbs B, Choi AH, Verheuvel NC, Solmi M, Pea A, Capelli P, et al: Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis. Eur J Surg Oncol. 42:919–925. 2016.PubMed/NCBI View Article : Google Scholar

85 

Li Y, Xiao H and Xue F: Overexpression of Klotho suppresses growth and pulmonary metastasis of osteosarcoma in vivo. Genet Mol Biol. 43(e20190229)2020.PubMed/NCBI View Article : Google Scholar

86 

Zhou X, Fang X, Jiang Y, Geng L, Li X, Li Y, Lu K, Li P, Lv X and Wang X: Klotho, an anti-aging gene, acts as a tumor suppressor and inhibitor of IGF-1R signaling in diffuse large B cell lymphoma. J Hematol Oncol. 10(37)2017.PubMed/NCBI View Article : Google Scholar

87 

Lambert AW, Pattabiraman DR and Weinberg RA: Emerging biological principles of metastasis. Cell. 168:670–691. 2017.PubMed/NCBI View Article : Google Scholar

88 

Ruijtenberg S and van den Heuvel S: Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression. Cell Cycle. 15:196–212. 2016.PubMed/NCBI View Article : Google Scholar

89 

Chen CD, Li H, Liang J, Hixson K, Zeldich E and Abraham CR: The anti-aging and tumor suppressor protein Klotho enhances differentiation of a human oligodendrocytic hybrid cell line. J Mol Neurosci. 55:76–90. 2015.PubMed/NCBI View Article : Google Scholar

90 

Fan J and Sun Z: The antiaging gene Klotho regulates proliferation and differentiation of adipose-derived stem cells. Stem Cells. 34:1615–1625. 2016.PubMed/NCBI View Article : Google Scholar

91 

Ahrens HE, Huettemeister J, Schmidt M, Kaether C and von Maltzahn J: Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle. Skelet Muscle. 8(20)2018.PubMed/NCBI View Article : Google Scholar

92 

Toan NK, Tai NC, Kim SA and Ahn SG: Soluble Klotho regulates bone differentiation by upregulating expression of the transcription factor EGR-1. FEBS Lett. 594:290–300. 2020.PubMed/NCBI View Article : Google Scholar

93 

Sárvári M, Kalló I, Hrabovszky E, Solymosi N, Rodolosse A, Vastagh C, Auer H and Liposits Z: Hippocampal gene expression is highly responsive to estradiol replacement in middle-aged female rats. Endocrinology. 156:2632–2645. 2015.PubMed/NCBI View Article : Google Scholar

94 

Lojkin I, Rubinek T, Orsulic S, Schwarzmann O, Karlan BY, Bose S and Wolf I: Reduced expression and growth inhibitory activity of the aging suppressor Klotho in epithelial ovarian cancer. Cancer Lett. 362:149–157. 2015.PubMed/NCBI View Article : Google Scholar

95 

Wolf I, Laitman Y, Rubinek T, Abramovitz L, Novikok I, Beeri R, Kuro-O M, Koeffler HP, Catane R, Freedman LS, et al: Functional variant of Klotho: A breast cancer risk modifier among BRCA1 mutation carriers of Ashkenazi origin. Oncogene. 29:26–33. 2010.PubMed/NCBI View Article : Google Scholar

96 

Mahmoud AM, Al-Alem U, Ali MM and Bosland MC: Genistein increases estrogen receptor beta expression in prostate cancer via reducing its promoter methylation. J Steroid Biochem Mol Biol. 152:62–75. 2011.PubMed/NCBI View Article : Google Scholar

97 

Li Y, Chen F, Wei A, Bi F, Zhu X, Yin S, Lin W and Cao W: Klotho recovery by genistein via promoter histone acetylation and DNA demethylation mitigates renal fibrosis in mice. J Mol Med (Berl). 97:541–552. 2019.PubMed/NCBI View Article : Google Scholar

98 

Oz OK, Hajibeigi A, Howard K, Cummins CL, van Abel M, Bindels RJ, Word RA, Kuro-o M, Pak CY and Zerwekh JE: Aromatase deficiency causes altered expression of molecules critical for calcium reabsorption in the kidneys of female mice *. J Bone Miner Res. 22:1893–1902. 2007.PubMed/NCBI View Article : Google Scholar

99 

Carrillo-López N, Román-García P, Rodríguez-Rebollar A, Fernández-Martín JL, Naves-Díaz M and Cannata-Andía JB: Indirect regulation of PTH by estrogens may require FGF23. J Am Soc Nephrol. 20:2009–2017. 2009.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Borges BC, Do Amaral PA, Soldi LR, Silva VL, De Souza FC, Cordeiro Da Luz FA, De Araújo RA and Silva MJ: Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer. Mol Clin Oncol 16: 93, 2022.
APA
Borges, B.C., Do Amaral, P.A., Soldi, L.R., Silva, V.L., De Souza, F.C., Cordeiro Da Luz, F.A. ... Silva, M.J. (2022). Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer. Molecular and Clinical Oncology, 16, 93. https://doi.org/10.3892/mco.2022.2526
MLA
Borges, B. C., Do Amaral, P. A., Soldi, L. R., Silva, V. L., De Souza, F. C., Cordeiro Da Luz, F. A., De Araújo, R. A., Silva, M. J."Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer". Molecular and Clinical Oncology 16.4 (2022): 93.
Chicago
Borges, B. C., Do Amaral, P. A., Soldi, L. R., Silva, V. L., De Souza, F. C., Cordeiro Da Luz, F. A., De Araújo, R. A., Silva, M. J."Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer". Molecular and Clinical Oncology 16, no. 4 (2022): 93. https://doi.org/10.3892/mco.2022.2526
Copy and paste a formatted citation
x
Spandidos Publications style
Borges BC, Do Amaral PA, Soldi LR, Silva VL, De Souza FC, Cordeiro Da Luz FA, De Araújo RA and Silva MJ: Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer. Mol Clin Oncol 16: 93, 2022.
APA
Borges, B.C., Do Amaral, P.A., Soldi, L.R., Silva, V.L., De Souza, F.C., Cordeiro Da Luz, F.A. ... Silva, M.J. (2022). Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer. Molecular and Clinical Oncology, 16, 93. https://doi.org/10.3892/mco.2022.2526
MLA
Borges, B. C., Do Amaral, P. A., Soldi, L. R., Silva, V. L., De Souza, F. C., Cordeiro Da Luz, F. A., De Araújo, R. A., Silva, M. J."Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer". Molecular and Clinical Oncology 16.4 (2022): 93.
Chicago
Borges, B. C., Do Amaral, P. A., Soldi, L. R., Silva, V. L., De Souza, F. C., Cordeiro Da Luz, F. A., De Araújo, R. A., Silva, M. J."Undetected αKlotho in serum is associated with the most aggressive phenotype of breast cancer". Molecular and Clinical Oncology 16, no. 4 (2022): 93. https://doi.org/10.3892/mco.2022.2526
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