Investigation of serum Seladin-1 / DHCR24 levels in breast cancer patients

Year 2020, Volume: 12 Issue: 3, 519 - 524, 20.10.2020

Attila Önmez , Onur Eşbah , İbrahim Ethem Şahin

https://doi.org/10.18521/ktd.785524

Abstract

Objective: Seladin-1, an enzyme that catalyzes the cholesterol formation reaction from desmosterol, has been shown to be expressed at different levels in various types of tumor. The purpose of this study was to investigate the relationship between serum seladin-1 levels and clinical characteristics of patients with non-metastatic breast cancer, and to examine the prognostic value of seladin-1 in breast cancer.

Method: Patients aged 18 and over diagnosed with breast cancer using histopathological methods at our medical oncology clinic, whose tumor tissue had been surgically removed and who had not yet received any oncological treatment, and with no distant organ metastasis or additional malignancy, and healthy women volunteers as a control group were included in the study. Demographic and laboratory data were recorded. Serum seladin-1 levels were compared between the patient and control groups.

Results: Seventy-three women, 46 patients and 27 controls, were enrolled. Mean ages were 56±12 years in the patient group and 62±12 in the control group (p=0.055) Seladin-1 levels were lower in the patient group than in the control group (p=0.038). No statistically significant relationship was observed between tumor size and seladin-1 levels (p=0.138). No relationship was also determined between patient grades and stages and seladin-1 (p=0.720; p=0.092, respectively).

Conclusion: Seladin-1 levels were lower in the serum of breast cancer patients than in the control group. However, no statistically significant relationship was found between breast cancer prognostic factors and seladin-1 levels. Further research is needed to clarify the mechanisms underlying the low seladin-1 levels in breast cancer patients.

Keywords

Breast cancer, , seladin-1, , DHCR24, , prognostic value

Meme kanserli hastalarda serum Seladin-1/DHCR24 düzeyinin araştırılması

Abstract

Amaç: Meme kanseri kadınlarda önemli bir morbidite ve mortalite nedenidir. Desmosterolden kolesterol oluşum reaksiyonunu katalizleyen enzim olan Seladin-1 daha önce çeşitli tümör türlerinde farklı düzeylerde exprese edildiği gözlenmiştir. Çalışmamızda; serum seladin-1 düzeyleri ile metastatik olmayan meme kanseri hastalarının klinik özellikleri arasındaki ilişkiyi ve seladin-1'in meme kanserinde prognostik değerini araştırmayı amaçladık.

Yöntem: Tıbbi onkoloji kliniğimizde, 18 yaş üstü, histopatolojik olarak meme kanseri tanısı almış, cerrahi olarak tümör dokusu çıkarılmış, herhangi bir onkolojik tedavi henüz almamış, uzak organ metastazı ve ek malignitesi olmayan hastalar ile kontrol grubu olarak sağlıklı kadın gönüller çalışmaya dahil edildi. Demografik veriler ve laboratuvar verileri kaydedildi. Serum seladin-1 düzeyleri hasta ve kontrol grupları arasında karşılaştırıldı.

Bulgular: 46 hasta ve 27 kontrol grubu olmak üzere toplam 73 kadın hasta çalışmaya dahil edildi. Hasta grubunun yaş ortalaması 56±12 yıl, kontrol grubunun 62±12 yıldı (p=0.055) Seladin-1 düzeyleri gruplar arasında karşılaştırıldığında; hasta grubunda kontrol grubuna göre daha düşük seviyede saptandı (p=0.038). Tümör boyutları ile Seladin-1 düzeyi arasında istatistiksel bir ilişki yoktu. (p=0.138). Bunun yanında, hastaların stage ve gradelerine göre seladin-1 düzeyi karşılaştırıldığında istatistiksel fark olmadığı görüldü (p=0,720; p=0,092, sırasıyla).

Sonuç: Çalışmamızda meme kanseri hastalarının serumlarında seladin-1 düzeyi kontrol grubuna göre daha düşük saptandı. Ne var ki, meme kanserinin prognostik faktörleri ile seladin-1 düzeylerinin ilişkili olmadığı görülmüştür. Seladin-1’in meme kanserli hastalarında düşük olmasının altında yatan mekanizmaların aydınlatılabilmesi için daha ileri araştırmalar gerekmektedir.

Keywords

Meme kanseri, Seladin-1, DHCR24, Prognostik değer

References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7-34.
• 2. Wollschläger D, Meng X, Wöckel A, Janni W, Kreienberg R, Blettner M, et al. Comorbidity‐ dependent adherence to guidelines and survival in breast cancer. Is there a role for guideline adherence in comorbid breast cancer patients? A retrospective cohort study with 2137 patients. The breast journal 2018;24:120-7.
• 3. DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin 2017;67:439-48.
• 4. Marcon M, Dedes K, Varga Z, Frauenfelder T, Boss A. Influence of breast cancer opportunistic screening on aesthetic surgical outcome: A single‐center retrospective study in Switzerland. The breast journal 2018;24:285-90.
• 5. Drzewinska J, Pulaski L, Soszynski M, Bartosz G. [Seladin-1/DHCR24: a key protein of cell homeostasis and cholesterol biosynthesis]. Postepy Hig Med Dosw (Online) 2009;63:318-30.
• 6. Iivonen S, Hiltunen M, Alafuzoff I, Mannermaa A, Kerokoski P, Puoliväli J, et al. Seladin-1 transcription is linked to neuronal degeneration in Alzheimer’s disease. Neuroscience 2002;113:301-10.
• 7. Waterham HR, Koster J, Romeijn GJ, Hennekam RC, Vreken P, Andersson HC, et al. Mutations in the 3β-hydroxysterol Δ24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis. The Am J Hum Genet 2001;69:685-94.
• 8. Lu X, Li Y, Wang W, Chen S, Liu T, Jia D, et al. 3 β-hydroxysteroid-Δ 24 reductase (DHCR24) protects neuronal cells from apoptotic cell death induced by endoplasmic reticulum (ER) stress. PloS one 2014;9:e86753.
• 9. Greeve I, Hermans-Borgmeyer I, Brellinger C, Kasper D, Gomez-Isla T, Behl C, et al. The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress. J Neuroscience 2000;20:7345-52.
• 10. Mirza R, Hayasaka S, Takagishi Y, Kambe F, Ohmori S, Maki K, et al. DHCR24 gene knockout mice demonstrate lethal dermopathy with differentiation and maturation defects in the epidermis. J Invest Derma 2006;126:638-47.
• 11. Kuehnle K, Crameri A, Kälin RE, Luciani P, Benvenuti S, Peri A, et al. Prosurvival effect of DHCR24/Seladin-1 in acute and chronic responses to oxidative stress. Mol Cell Bio 2008;28:539-50.
• 12. Doherty SC, McKeown SR, Lopez JA, Walsh IK, McKelvey-Martin VJ. Gene expression in normal urothelium depends on location within the bladder: a possible link to bladder carcinogenesis. Eur Urol 2006;50:290-301.
• 13. Sarkar D, Imai T, Kambe F, Shibata A, Ohmori S, Siddiq A, et al. The human homolog of Diminuto/Dwarf1 gene (hDiminuto): a novel ACTH-responsive gene overexpressed in benign cortisol-producing adrenocortical adenomas. J Clin Endoc Metab 2001;86:5130-7.
• 14. Luciani P, Gelmini S, Ferrante E, Lania A, Benvenuti S, Baglioni S, et al. Expression of the antiapoptotic gene seladin-1 and octreotide-induced apoptosis in growth hormone-secreting and nonfunctioning pituitary adenomas. J Clin Endoc Metab 2005;90:6156-61.
• 15. Bonaccorsi L, Luciani P, Nesi G, Mannucci E, Deledda C, Dichiara F, et al. Androgen receptor regulation of the seladin-1/DHCR24 gene: altered expression in prostate cancer. Laboratory investigation 2008;88:1049.
• 16. Di Stasi D, Vallacchi V, Campi V, Ranzani T, Daniotti M, Chiodini E, et al. DHCR24 gene expression is upregulated in melanoma metastases and associated to resistance to oxidative stress‐induced apoptosis. Inter J Cancer 2005;115:224-30.
• 17. Dai M, Zhu X-L, Liu F, Xu Q-Y, Ge Q-L, Jiang S-H, et al. Cholesterol synthetase DHCR24 induced by insulin aggravates cancer invasion and progesterone resistance in endometrial c arcinoma. Sci Report 2017;7:41404.
• 18. Crameri A, Biondi E, Kuehnle K, Lutjohann D, Thelen KM, Perga S, et al. The role of seladin- 1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo. Embo J 2006;25:432-43.
• 19. Benvenuti S, Luciani P, Vannelli GB, Gelmini S, Franceschi E, Serio M, et al. Estrogen and selective estrogen receptor modulators exert neuroprotective effects and stimulate the expression of selective Alzheimer’s disease indicator-1, a recently discovered antiapoptotic gene, in human neuroblast long-term cell cultures. J Clin Endoc Metab 2005;90:1775-82.
• 20. Su AI, Welsh JB, Sapinoso LM, Kern SG, Dimitrov P, Lapp H, et al. Molecular classification of human carcinomas by use of gene expression signatures. Cancer Res. 2001;61:7388-93.
• 21. Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, et al. Large-scale analysis of the human and mouse transcriptomes. Proc Nat Acad Sci 2002;99:4465-70.
• 22. Benvenuti S, Luciani P, Cellai I, Deledda C, Baglioni S, Saccardi R, et al. Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors. J Endoc 2008;197:437-46.
• 23. Wu C, Miloslavskaya I, Demontis S, Maestro R, Galaktionov K. Regulation of cellular response to oncogenic and oxidative stress by Seladin-1. Nature 2004;432:640.
• 24. Arispe N, Doh M. Plasma membrane cholesterol controls the cytotoxicity of Alzheimer’s disease AβP (1–40) and (1–42) peptides. FASEB J. 2002;16:1526-36.
• 25. Sista F, Abruzzese V, Clementi M, Carandina S, Amicucci G. Effect of resected gastric volume on ghrelin and GLP-1 plasma levels: a prospective study. J Gastrointes Sur 2016;20:1931-41.
• 26. Luciani P, Ferruzzi P, Arnaldi G, Crescioli C, Benvenuti S, Nesi G, et al. Expression of the novel adrenocorticotropin-responsive gene selective Alzheimer’s disease indicator-1 in the normal adrenal cortex and in adrenocortical adenomas and carcinomas. J Clin Endoc Metab 2004;89:1332-9.
• 27. Simi L, Malentacchi F, Luciani P, Gelmini S, Deledda C, Arvia R, et al. Seladin-1 expression is regulated by promoter methylation in adrenal cancer. BMC cancer 2010;10:201.
• 28. Battista MC, Guimond MO, Roberge C, Doueik AA, Fazli L, Gleave M, et al. Inhibition of DHCR24/Seladin‐1 impairs cellular homeostasis in prostate cancer. The Prostate 2010;70:921-33.