Possible role of the receptor of advanced glycation end products (RAGE) in the clinical course of prostate neoplasia in patients with and without type 2 diabetes mellitus
Corresponding Author
Gamze Akkus
Department of Endocrinology, Cukurova University, Adana, Turkey
Search for more papers by this authorVolkan Izol
Department of Urology, Cukurova University, Adana, Turkey
Search for more papers by this authorFesih Ok
Department of Urology, Cukurova University, Adana, Turkey
Search for more papers by this authorMehtap Evran
Department of Endocrinology, Cukurova University, Adana, Turkey
Search for more papers by this authorMerve Inceman
Department of Pathology, Cukurova University, Adana, Turkey
Search for more papers by this authorSeyda Erdogan
Department of Pathology, Cukurova University, Adana, Turkey
Search for more papers by this authorHalil Mahir Kaplan
Department of Pharmacology, Cukurova University, Adana, Turkey
Search for more papers by this authorMurat Sert
Department of Endocrinology, Cukurova University, Adana, Turkey
Search for more papers by this authorTamer Tetiker
Department of Endocrinology, Cukurova University, Adana, Turkey
Search for more papers by this authorCorresponding Author
Gamze Akkus
Department of Endocrinology, Cukurova University, Adana, Turkey
Search for more papers by this authorVolkan Izol
Department of Urology, Cukurova University, Adana, Turkey
Search for more papers by this authorFesih Ok
Department of Urology, Cukurova University, Adana, Turkey
Search for more papers by this authorMehtap Evran
Department of Endocrinology, Cukurova University, Adana, Turkey
Search for more papers by this authorMerve Inceman
Department of Pathology, Cukurova University, Adana, Turkey
Search for more papers by this authorSeyda Erdogan
Department of Pathology, Cukurova University, Adana, Turkey
Search for more papers by this authorHalil Mahir Kaplan
Department of Pharmacology, Cukurova University, Adana, Turkey
Search for more papers by this authorMurat Sert
Department of Endocrinology, Cukurova University, Adana, Turkey
Search for more papers by this authorTamer Tetiker
Department of Endocrinology, Cukurova University, Adana, Turkey
Search for more papers by this authorAbstract
Aim
The expression of the cognate receptor of advanced glycation end products (RAGE) in malignant tissues of patients with type 2 diabetes has been suggested as a co-factor determining the clinical course and prognosis. We aimed to investigate the relationship between RAGE expression and clinicopathological features of prostate neoplasia.
Methods
Tissue samples of 197 patients, 64 (24 patients with type 2 diabetes and 40 controls) with benign prostate hyperplasia (BPH) and 133 (71 patients with type 2 diabetes and 62 controls) with localised or metastatic prostate cancer (LPCa/MetPCa) were included in the study. The expression of RAGE in prostate specimens was studied immunohistochemically. RAGE scores were determined according to the extent of immunoreactivity and staining intensity.
Results
RAGE expression in BPH group (patients with type 2 diabetes and controls) was negative. Patients with both LPCa and MetPCa had significantly higher scores than those with BPH (P < .001). The mean RAGE scores of patients with type 2 diabetes LPCa and MetPCa were 4.71 ± 3.14 and 4.97 ± 3.69. The mean scores of control LPCa and MetPCa were 1.52 ± 1.87 and 1.69 ± 1.58, respectively. The scores of patients with type 2 diabetes LPCa and MetPCa were significantly higher than those of control LPCa and MetPCa (P = .01 and P < .001, respectively).
Conclusion
We found higher RAGE expression levels in malignant prostate neoplasia than in BPH. As expected, patients with diabetes had higher scores than control patients. Disease progression and survival parameters were worse in patients with high RAGE levels. RAGE expression may be a useful biomarker for the diagnosis and prognosis of prostate cancer.
DISCLOSURE
We declare that there was no conflict of interest.
REFERENCES
- 1Giovannuci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010; 33: 1674-1685.
- 2Peairs KS, Barone BB, Snyder CF, et al. Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J Clin Oncol. 2011; 29: 40-46.
- 3Tan BX, Yao WX, Ge J, et al. Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes. Cancer. 2011; 117: 5103-5111.
- 4Larsson SC, Wolk A. Diabetes mellitus and incidence of kidney cancer: a meta-analysis of cohort studies. Diabetologia. 2011; 54: 1013-1018.
- 5Feng X, Wang G, Li N, et al. The association between fasting blood glucose and the risk of primary liver cancer in Chinese males: a population-based prospective study. Br J Cancer. 2017; 117: 1405.
- 6Fall K, Garmo H, Gudbjornsdottir S, et al. Diabetes mellitus and prostate cancer risk: a nationwide case-control study within PCBaSe Sweden. Cancer Epidemiol Biomarkers Prev. 2013; 22: 1102-1109.
- 7Bonovas S, Filioussi K, Tsantes A. Diabetes mellitus and risk of prostate cancer: a meta-analysis. Diabetologia. 2004; 47: 1071-1078.
- 8Kasper J, Giovannucci E. A meta-analysis of diabetes mellitus and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2006; 15: 2056.
- 9Lawrence YR, Morag O, Benderly M, et al. Association between metabolic syndrome, diabetes mellitus and prostate cancer risk. Prostate Cancer Prostatic Dis. 2013; 16: 181-186.
- 10Rodriguez C, Patel AV, Mondul AM, Jacobs EJ, Thun MJ, Calle EE. Diabetes and risk of prostate cancer in a prospective cohort of US men. Am J Epidemiol. 2005; 161: 147-152.
- 11Tseng CH. Diabetes and risk of prostate cancer: a study using the National Health Insurance. Diabetes Care. 2011; 34: 616-621.
- 12Li Q, Kuriyama S, Kakizaki M, et al. History of diabetes mellitus and the risk of prostate cancer: the Ohsaki Cohort Study. Cancer Causes Control. 2010; 21: 1025-1032.
- 13Peehl DM, Stamey TA. Serum-free growth of adult human prostatic epithelial cells. Vitro Cell Dev Biol. 1986; 22: 82-90.
- 14Wright JL, Plymate SR, Porter MP, et al. Hyperglycemia and prostate cancer recurrence in men treated for localized prostate cancer. Prostate Cancer Prostatic Dis. 2013; 16: 204-208.
- 15Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001; 44: 129-146.
- 16Ahmed N, Thornalley PJ. Advanced glycation endproducts: what is their relevance to patients with type 2 diabetes complications? Diabetes Obes Metab. 2007; 9: 233-245.
- 17Monnier VM, Sell DR, Nagaraj RH, et al. Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging, and uremia. Diabetes. 1992; 41: 36-41. https://doi.org/10.2337/diab.41.2.S36
- 18Goh SY, Cooper ME. Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab. 2008; 93: 1143-1152.
- 19Li T, Qin W, Liu Y, et al. Effect of RAGE gene polymorphisms and circulating sRAGE levels on susceptibility to gastric cancer: a case-control study. Cancer Cell Int. 2017.
- 20Nankali M, Karimi J, Goodarzi M, et al. Increased expression of the receptor for advanced glycation end-products (RAGE) is associated with advanced breast cancer stage. Oncol Res Treat. 2016; 39: 622-628.
- 21Nguyen AH, Detty SQ, Agrawal DK. Clinical implications of high-mobility group box-1 (HMGB1) and the receptor for advanced glycation end-products (RAGE) in cutaneous malignancy: a systematic review. Anticancer Res. 2017; 37: 1-7.
- 22Kang R, Tang D, Schapiro NE, et al. The HMGB1/RAGE inflammatory pathway promotes pancreatic tumor growth by regulating mitochondrial bioenergetics. Oncogene. 2014; 33: 567-577.
- 23Yang S, Pinney SM, Mallick P, et al. Impact of oxidative stress biomarkers and carboxymethyllysine (an advanced glycation end product) on prostate cancer: a prospective study. Clin Genitourin Cancer. 2015; 13: 347-351.
- 24Epstein JI, Egevad L, Amin MB, et al. The 2014 International Society of Urological Pathology (ISUP) consensus conference on gleason grading of prostatic carcinoma. Am J Surg Pathol. 2016; 40: 244-249. https://doi.org/10.1097/PAS.0000000000000530
- 25Moul JW. Prostate specific antigen only progression of prostate cancer. J Urol. 2000; 163: 1632-1642.
- 26Trock BJ, Han M, Freedland SJ, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA. 2008; 299: 27609.
- 27Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). EJC. 2009; 45: 228-247.
- 28Xu XC, Abuduhadeer X, Zhang WB, et al. Knockdown of RAGE inhibits growth and invasion of gastric cancer Cells. Eur J Histochem. 2013; 29: 240-246.
- 29Ishiguro H, Nakaigawa N, Miyoshi Y, Fujinami K, Kubota Y, Uemura H. Receptor for advanced glycation end products (RAGE) and its ligand, amphoterin are overexpressed and associated with prostate cancer development. Prostate. 2005; 64: 92-100.
- 30Cai H, Xu Z, Xu T, et al. Diabetes mellitus is associated with elevated risk of mortality amongst patients with prostate cancer: a meta-analysis of 11 cohort studies. Diabetes Metab Res Rev. 2015; 31: 336-343.
- 31Chen M, Luo Y, Yang S, et al. Association of diabetes mellitus with prostate cancer grade and prostate-specific antigen in Chinese biopsy population. Diabetes Res Clin Pract. 2018; 141: 80-87.
- 32Tsilidis KK, Allen NE, Appleby PN, et al. Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2015; 136: 372-381.
- 33Xu H, Jiang HW, Ding GX, et al. Diabetes mellitus and prostate cancer risk of different grade or stage: a systematic review and meta-analysis. Diabetes Clin Res Pract. 2013; 99: 241-249.
- 34Moreira DM, Anderson T, Gerber L, et al. The association of diabetes mellitus and high-grade prostate cancer in a multiethnic biopsy series. Cancer Causes Control. 2011; 22: 977-983.
- 35Fukushima H, Masuda H, Kawakami S, et al. Effect of diabetes mellitus on high-grade prostate cancer detection among Japanese obese patients with prostate-specific antigen less than 10 ng/mL. Urology. 2012; 79: 1329-1334.
- 36Betancourt-Albrecht M, Cunningham GR. Hypogonadism and diabetes. Int J Impot Res. 2003; 15: S14-S20.
- 37Peskoe SB, Joshu CE, Rohrmann S, et al. Circulating total testosterone and PSA concentrations in a nationally representative sample of men without a diagnosis of prostate cancer. Prostate. 2015; 75: 1167-1176.
- 38Barrett-Connor E. Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Ann Intern Med. 1992; 117: 807-811.
- 39Baillargeon J, Pollock BH, Kristal AR, et al. The association of body mass index and prostate-specific antigen in a population-based study. Cancer. 2005; 103: 1092-1095.
- 40McGinley KF, McMahon GC, Brown GA. Impact of the US Preventive Services Task Force Grade D recommendation: assessment of evaluations for elevated prostate-specific antigen and prostate biopsies in a large urology group practice following statement revision. Rev Urol. 2015; 17: 171-177.
- 41Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003; 289: 76-79.
- 42Drinda S, Franke S, Rüster M, et al. Identification of the receptor for advanced glycation end products in synovial tissue of patients with rheumatoid arthritis. Rheumatol Int. 2005; 25: 411-413.
- 43Hu P, Lai D, Lu P, Gao J, He H. ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells. Int J Mol Med. 2012; 29: 613-618.
- 44Yuan X, Zhang Z, Gong K, Zhao P, Qin J, Liu N. Inhibition of reactive oxygen species/extracellular signal-regulated kinases pathway by pioglitazone attenuates advanced glycation end products-induced proliferation of vascular smooth muscle cells in rats. Biol Pharm Bull. 2011; 34: 618-623.
- 45Zhang J, Shao S, Han D, et al. High mobility group box 1 promotes the epithelial-to-mesenchymal transition in prostate cancer PC3 cells via the RAGE/NF-κB signaling pathway. Int J Oncol. 2018; 53: 659-671.
- 46Zhao C, Bao J, Lu Y, et al. Co-expression of RAGE and HMGB1 is associated with cancer progression and poor patient outcome of prostate cancer. Am J Cancer Res. 2014; 4: 369.
- 47Tateno T, Ueno S, Hiwatashi K, et al. Expression of receptor for advanced glycation end products (RAGE) is related to prognosis in patients with esophageal squamous cell carcinoma. Ann Surg Oncol. 2009; 16: 440-446.
- 48Fahmueller YN, Nagel D, Hoffmann R-T, et al. Immunogenic cell death biomarkers HMGB1, RAGE, and DNAse indicate response to radioembolization therapy and prognosis in colorectal cancer patients. Int J Cancer. 2013; 132: 2349-2358.
