Prognostic Value of SPARC Expression in Unresectable NSCLC Treated with Concurrent Chemoradiotherapy

  • Kurtul, Neslihan (Department of Radiation Oncology, Sutcu Imam University Medical Faculty) ;
  • Eroglu, Celalettin (Department of Radiation Oncology, Erciyes University Medical Faculty) ;
  • Unal, Dilek (Department of Radiation Oncology, Kayseri Education and Research Hospital) ;
  • Tasdemir, Erdem Arzu (Department of Pathology, Kayseri Education and Research Hospital) ;
  • Orhan, Okan (Department of Radiation Oncology, Erciyes University Medical Faculty) ;
  • Zararsiz, Gokmen (Department of Biostatistics and Medical Informatics, Erciyes University Medical Faculty) ;
  • Baran, Munevver (Department of Pathology, Erciyes University Medical Faculty) ;
  • Kaplan, Bunyamin (Department of Radiation Oncology, Erciyes University Medical Faculty) ;
  • Kontas, Olgun (Department of Pathology, Erciyes University Medical Faculty)
  • 발행 : 2014.11.06


Background: The aim of the present study was to determine the predictive/prognostic value of the secreted protein, acidic and rich in cysteine (SPARC) in cases of unresectable, locally advanced, non-small cell lung cancer. Materials and Methods: The study included 84 patients with Stage IIIA-B non-small cell lung cancer, undergoing simultaneous chemoradiotherapy including radiotherapy at a dose of 66 Gy and weekly docataxel ($20mg/m^2$) and cisplatin ($20mg/m^2$). SPARC expression was studied in biopsy material by immunohistochemical methods and correlations with treatment responses or survival were evaluated. Results: Median overall survival was $16{\pm}2.73$ (11.55-20.46) months for low expression vs $7{\pm}1.79$ months (7.92-16.08) months for high expression (p=0.039), while median local control was $13{\pm}2.31$ (8.48-17.5) months for low expression vs $6{\pm}0.85$ (4.34-7.66) months for high expression (p=0.045) and median progression-free survival was $10{\pm}2.31$ (5.48-14.5) months for low expression vs $6{\pm}1.10$ (3.85-8.15) months for high expression (p=0.022). In both univariate and multivariate analyses, high SPARC expression was associated with significantly shorter overall survival (p=0.003, p=0.007, respectively), local control (p=0.008, p=0.036) and progression-free survival (p=0.004, p=0.029) when compared to low SPARC expression. No significant difference was detected between high and low SPARC expression groups regarding age, sex, T stage, N stage, histopathology and stage-related patient characteristics. Conclusions: High SPARC expression was identified as a poor prognostic factor in cases with locally advanced NSCLC treated with concurrent chemoradiotherapy.


연구 과제 주관 기관 : Erciyes University


  1. Desai N, Trieu V, Damascelli B, et al (2009). SPARC expression correlates with tumor response to albumin-bound paclitaxel in head and neck cancer patients. Transl Oncol, 2, 59-64.
  2. Cheetham S, Tang MJ, Mesak F, et al (2008). SPARC promoter hypermethylation in colorectal cancers can be reversed by 5-Aza-2' deoxycytidine to increase SPARC expression and improve therapy response. Br J Cancer, 98, 1810-9.
  3. Chin D, Boyle GM, Williams RM, et al (2005). Novel markers for poorprognosis in head and neck cancer. Int J Cancer, 113, 789-97.
  4. Chlenski A, Cohn SL (2010). Modulation of matrix remodeling by SPARC in neoplastic progression. Semin Cell Dev Biol, 21, 55-65.
  5. DiMartino JF, Lacayo NJ, Varadi M, et al (2006). Low or absent SPARC expression in acute myeloid leukemia with MLL rearrangements is associated with sensitivity to growth inhibition by exogenous SPARC protein. Leukemia, 20, 426-32.
  6. Huang Y, Zhang J, Zhao YY, et al (2012). SPARC expression and prognostik value in non-small cell lung cancer. Chinese J Cancer, 31, 541-8.
  7. Gradishar WJ, Tjulandin S, Davidson N, et al (2005). Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol, 23, 7794-803.
  8. Gradishar WJ (2006). Albumin-bound paclitaxel: a nextgeneration taxane. Expert Opin Pharmacother, 7, 1041-53.
  9. Grant JL, Fishbein MC, Hong LS, et al (2014). A novel molecular pathway for snail-dependent, SPARC-mediated invasion in non-small cell lung cancer pathogenesis. Cancer Prev Res, 7, 150-60.
  10. Infante JR, Matsubayashi H, Sato N, et al (2007). Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol, 25, 319-25.
  11. Kaufmann B, Muller S, Hanisch FG, et al (2004). Structural variability of BM-40/SPARC/osteonectin glycosylation: implications for collagen affinity. Glycobiology, 14, 609-19.
  12. Koukourakis MI, Giatromanolaki A, Brekken RA, et al (2003). Enhanced expression of SPARC/osteonectin in the tumorassociated stroma of non-sm all cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis ofpatients. Cancer Res, 63, 5376-80.
  13. Miyoshi K, Sato N, Ohuchida K, Mizumoto K, Tanaka M (2010). SPARC Mrna expression as a prognostic marker for pancreatic adeno-carcinoma patients. Anticancer Res, 30, 867-71.
  14. Nagai MA, Gerhard R, Fregnani JH, et al (2010). Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients. Breast Cancer Res Treat, 126, 1-14.
  15. Sato T, Oshima T, Yamamoto N, et al (2013). Clinical aignificance of SPARC gene expression in patients with gastric cancer. J Surg Oncol, 108, 364-8.
  16. Oguz A, Unal D, Tasdemir A, et al (2013). Lack of any association between blood groups and lung cancer, independent of histology. Asian Pac J Cancer Prev, 14, 453-6.
  17. Podhajcer OL, Benedetti LG, Girotti MR, et al (2008). The role of the matricellular protein SPARC in the dynamic interaction between the tumor and the host. Cancer Metastasis Rev, 27, 691-705.
  18. Said N, Socha MJ, Olearczyk JJ, et al (2007). Normalization of the ovarian cancer microenvironment by SPARC. Mol Cancer Res, 5, 1015-30.
  19. Schiemann BJ, Neil JR, Schiemann WP (2003). SPARC inhibits epithelial cell proliferation in part through stimulation of the transforming growth factor-be ta-signaling system. Mol Biol Cell, 14, 3977-88.
  20. Schneider S, Yochim J, Brabender J, et al (2004). Osteopontin but not osteonectin messenger RNA expression is a prognostic marker in curatively resected non-small cell lung cancer. Clin Cancer Res, 10, 1588-96.
  21. Siddiq F, Sarkar FH, Wali A, Pass HI, Lonardo F (2004). Increased osteonectin expression is associated with malignant transformation and tumor associated fibrosis in the lung. Lung Cancer, 45, 197-205
  22. Socinski MA, Bondarenko IN, Karaseva NA, et al (2010). Results of a randomized, phase III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophorbased paclitaxel (P) and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC). J Clin Oncol, 28, 18.
  23. Watkins G, Douglas-Jones A, Bryce R, et al (2005). Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes. Prostaglandins Leukot Essent Fatty Acids, 72, 267-72.
  24. Taghizadeh F, Tang MJ, Tai IT (2007). Synergism between vitamin D and secreted protein acidic and rich in cysteine-in duced apoptosis and growth inhibition results in increased susceptibility of therapy-resistant colorectal cancer cells to chemotherapy. Mol Cancer Ther, 6, 309-17.
  25. Tai IT, Tang MJ (2008). SPARC in cancer biology: its role in cancer progression and potential for therapy. Drug Resist Updat, 11, 231-46.
  26. Tsao MS, Aviel-Ronen S, Dink K, et al (2007). Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer. J Clin Oncol, 20, 5240-7.
  27. Wu GQ, Liu NN, Xue XL, et al (2014). Multiplex real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of response of non-small cell lung cancer to chemoradiotherapy. Asian Pac J Cancer Prev, 15, 4153-8.
  28. Xie KJ, He HE, Sun AJ, et al (2014). Expression of ERCC1, MSH2 and PARP1 in non-small cell lung cancer and prognostic value in patients treated with platinum-based chemotherapy. Asian Pac J Cancer Prev, 15, 2591-6.
  29. Yiu GK, Chan WY, Ng SW, et al (2001). SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. Am J Pathol, 159, 609-22.
  30. Zhang Z, Wang Z, Liu X, et al (2012). Correlation of KLF4 and SPARC Expression with the clinical characteristics of non-small cell lung cancer. Chin J Lung Cancer, 15, 720-14.

피인용 문헌

  1. Prognostic Value of SPARC in Patients with Pancreatic Cancer: A Systematic Review and Meta-Analysis vol.11, pp.1, 2016,
  2. Thy-1+ Cancer-associated Fibroblasts Adversely Impact Lung Cancer Prognosis vol.7, pp.1, 2017,