Over-Expression of Osteopontin as Potential Predictive Biomarker for Bladder Cancer Treatment

Andy Zulfiqqar, Indrawarman Soerohardjo, Sumadi Lukman Anwar


Background: Current options for management of bladder cancer (BCa) still depend on traditional clinical determinants of stage and histological grade which often do not reflect the biological entity of the tumors. Therefore, new biomarkers are required to better determine suitable treatments for different types of bladder cancers. Recent research has shown osteopontin (OPN) expressions correlate with clinic-pathological variables and outcomes of bladder cancer. This study aimed to evaluate the expression of OPN in the Indonesian population, and it’s potential role as an immune-targeting therapy of BCa.

Methods: Total RNAs from formalin-fixed paraffin-embedded tissues were extracted from 49 patients with bladder cancer consisting of normal histopathology (n = 4), chronic cystitis (n = 15), non-muscle-invasive bladder cancer (NMIBC, n = 15), and muscle-invasive breast cancer (MIBC, n = 15). The expression of OPN was measured using reverse transcription-polymerase chain reaction.

Results: The baseline clinical and histo-pathological characteristics were not statistically different. The expression of OPN was statistically higher in bladder cancer compared to normal histology tissues (P < .001). The expression of OPN was statistically higher in MIBC compared to NMIBC (P < .001).

Conclusions: The expression of OPN was significantly higher in bladder cancer and compared to NIMBC, the OPN expression in MIBC was significantly higher rendering the potential role of OPN expression as a surrogate biomarker marker to determine suitable treatment options for patients with bladder cancer.


bladder cancer, biomarkers, osteopontin, targeting therapy


Burger M, Catto JWF, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234–41.

Cumberbatch MGK, Jubber I, Black PC, Esperto F, Figueroa JD, Kamat AM, et al. Epidemiology of bladder cancer: A systematic review and contemporary update of risk factors in 2018. Eur Urol. 2018;74(6):784–95.

Collaboration GB of DC, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study. JAMA Oncol. 2017 Apr 1;3(4):524–48.

Richters A, Aben KKH, Kiemeney LALM. The global burden of urinary bladder cancer: an update. World J Urol. 2019;10.1007/s00345-019-02984-4.

Babjuk M, Burger M, Comperat E, Gontero P, Mostafid A. European Association of Urology - Guidelines-Non-muscle-invasive-Bladder-Cancer-TaT1-CIS-2018. 2018;8–30. Available from: http://uroweb.org/wp-content/uploads/EAU-Guidelines-Non-muscle-invasive-Bladder-Cancer-TaT1-CIS-2018.pdf

Kwon T, Jeong IG, You D, Hong B, Hong JH, Ahn H, et al. Long-term oncologic outcomes after radical cystectomy for bladder cancer at a single institution. J Korean Med Sci. 2014;29(5):669–75.

Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–66.

Shabsigh A, Korets R, Vora KC, Brooks CM, Cronin AM, Savage C, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol. 2009;55(1):164–76.

Yakovlev P, Klyushin DA, Vereshchako RI. Bladder sparing surgery in high-grade bladder cancer. Exp Oncol. 2019;41(2):160–5.

Cahn DB, Handorf EA, Ghiraldi EM, Ristau BT, Geynisman DM, Churilla TM, et al. Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer. Cancer. 2017;123(22):4337–45.

Siefker-Radtke AO, Kamat AM, Corn PG, Matin SF, Grossman HB, Millikan RE, et al. Neoadjuvant chemotherapy with DD-MVAC and bevacizumab in high-risk urothelial cancer: Results from a phase II trial at the M. D. Anderson Cancer Center. J Clin Oncol. 2012;30(5_suppl):261.

Powles T, Durán I, van der Heijden MS, Loriot Y, Vogelzang NJ, De Giorgi U, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018;391(10122):748–57.

Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909–20.

Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18(3):312–22.

Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee J-L, Fong L, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med. 2017;376(11):1015–26.

Patel MR, Ellerton J, Infante JR, Agrawal M, Gordon M, Aljumaily R, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol. 2018;19(1):51–64.

Marin-Acevedo JA, Chirila RM, Dronca RS. Immune checkpoint inhibitor toxicities. Mayo Clin Proc. 2019;94(7):1321–9.

Wei R, Wong JPC, Kwok HF. Osteopontin -- a promising biomarker for cancer therapy. J Cancer. 2017;8(12):2173–83.

Cao D-X, Li Z-J, Jiang X-O, Lum YL, Khin E, Lee NP, et al. Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers. World J Gastroenterol. 2012;18(30):3923–30.

Yang G-H, Fan J, Xu Y, Qiu S-J, Yang X-R, Shi G-M, et al. Osteopontin combined with CD44, a novel prognostic biomarker for patients with hepatocellular carcinoma undergoing curative resection. Oncologist. 2008;13(11):1155–65.

Han X, Wang W, He J, Jiang L, Li X. Osteopontin as a biomarker for osteosarcoma therapy and prognosis. Oncol Lett. 2019;17(3):2592–8.

Zhao H, Chen Q, Alam A, Cui J, Suen KC, Soo AP, et al. The role of osteopontin in the progression of solid organ tumour. Cell Death Dis. 2018;9(3):356.

Saleh S, Thompson DE, McConkey J, Murray P, Moorehead RA. Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells. BMC Cancer. 2016;16(1):359.

Butti R, Ghosh P, Totakura KVS. Role of osteopontin in Tumor microenvirontment: A new paradigm in Cancer therapy. In: Gandhi V, Mehta K, Grover R, Pathak S, Aggarwal BB, editor. Multi-targeted approach to treat cancer. Houston: Springer, 2015. p. 113–25.

Śmieszek A, Basińska K, Chrząstek K, Marycz K. In vitro and in vivo effects of metformin on osteopontin expression in mice adipose-derived multipotent stromal cells and adipose tissue. J Diabetes Res. 2015;2015:814896.

Tang H, Wang J, Bai F, Hong L, Liang J, Gao J, et al. Inhibition of osteopontin would suppress angiogenesis in gastric cancer. Biochem Cell Biol. 2007;85(1):103–10.

Castello LM, Raineri D, Salmi L, Clemente N, Vaschetto R, Quaglia M, et al. Osteopontin at the crossroads of inflammation and tumor progression. Mediators Inflamm. 2017;2017:4049098.

Weber GF, Cantor H. Weber GF, Cantor HDifferential roles of osteopontin/Eta-1 in early and late lpr disease. Clin Exp Immunol 126:578-583. Clin Exp Immunol. 2002;126:578–83.

O’Regan AW, Hayden JM, Berman JS. Osteopontin augments CD3-mediated interferon-γ and CD40 ligand expression by T cells, which results in IL-12 production from peripheral blood mononuclear cells. J Leukoc Biol. 2000;68(4):495–502.

Lund SA, Giachelli CM, Scatena M. The role of osteopontin in inflammatory processes. J Cell Commun Signal. 2009;3(3–4):311–22.

Oates AJ, Barraclough R, Rudland PS. The identification of osteopontin as a metastasis-related gene product in a rodent mammary tumour model. Oncogene. 1996;13(1):97–104.

Wong JPC, Wei R, Lyu P, Tong OLH, Zhang SD, Wen Q, et al. Clinical and in vitro analysis of Osteopontin as a prognostic indicator and unveil its potential downstream targets in bladder cancer. Int J Biol Sci. 2017;13(11):1373–86.

Hussain SA, Palmer DH, Syn W-K, Sacco JJ, Greensmith RMD, Elmetwali T, et al. Gene expression profiling in bladder cancer identifies potential therapeutic targets. Int J Oncol. 2017;50(4):1147–59.

Wang ZM, Cui YH, Li W, Chen SY, Liu TS. Lentiviral-mediated siRNA targeted against osteopontin suppresses the growth and metastasis of gastric cancer cells. Oncol Rep. 2011;25(4):997–1003.

Gong M, Lu Z, Fang G, Bi J, Xue X. A small interfering RNA targeting osteopontin as gastric cancer therapeutics. Cancer Lett. 2008;272(1):148‐159. doi:10.1016/j.canlet.2008.07.004

Śmieszek A, Basińska K, Chrząstek K, Marycz K. In Vitro and In Vivo Effects of Metformin on Osteopontin Expression in Mice Adipose-Derived Multipotent Stromal Cells and Adipose Tissue. J Diabetes Res [Internet]. 2015/04/30. 2015;2015:814896. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26064989

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DOI: 10.33371/ijoc.v14i2.709

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