Targeted Oncology

, Volume 14, Issue 2, pp 187–195 | Cite as

Serum Alpha1-Globulin as a Novel Prognostic Factor in Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors

  • Xiang Chen
  • JiaXi Yao
  • Li Liu
  • WenZhong Zheng
  • XiaoYi HuEmail author
  • YanJun Zhu
  • Hang Wang
  • JianMing GuoEmail author
Original Research Article



Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown.


We conducted this study to explore the prognostic value of SPF in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors and its association with clinical characteristics.


Patients with mRCC (n = 213) who initiated first-line sunitinib or sorafenib systemic therapy for metastatic disease between March 2007 and June 2017 at Zhongshan Hospital, Fudan University, were retrospectively included in our analysis. Clinical and pathological data were collected. SPF was measured by capillary electrophoresis. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model. Correlation was estimated with Spearman’s correlation coefficient.


Among all SPF components, high α1-globulin was an independent prognostic factor for OS and PFS (dichotomized by median, hazard ratio [HR] 2.356; 95% confidence interval [CI] 1.399–3.966, p = 0.001; and HR 1.994; 95% CI 1.360–2.923, p < 0.001, respectively). In our cohort, α1-globulin showed better predictive value for OS than the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model (C-index 0.682 vs. 0.597; p = 0.005). Moreover, serum α1-globulin was positively correlated with International Society of Urological Pathology (ISUP) grade (r = 0.237; p < 0.001), tumor size (r = 0.242; p < 0.001), initial tumor/node/metastasis (TNM) stage (r = 0.185; p = 0.007), and IMDC risk group (r = 0.485; p < 0.001).


High serum α1-globulin correlates with high tumor load. Serum α1-globulin is an independent prognostic factor of OS and PFS in mRCC and demonstrates better predictive value for OS than does the IMDC model.



The authors sincerely thank Ms. YaoYi Gao (Department of Laboratory Medicine, Zhongshan Hospital, Fudan University) for providing information on methodology around SPE.

Compliance with Ethical Standards


This research was supported by grants from the National Natural Science Foundation of China (81772696, 81472376, and 81702496).

Conflict of interest

Xiang Chen, JiaXi Yao, Li Liu, WenZhong Zheng, XiaoYi Hu, YanJun Zhu, Hang Wang, and JianMing Guo have no conflicts of interest that might be relevant to the contents of this manuscript.

Supplementary material

11523_2019_625_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1880 kb)


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30. Scholar
  2. 2.
    Ljungberg B, Albiges L, Bensalah K, Bex A, Giles RH, Hora M et al. EAU guidelines on renal cell carcinoma. 2017. Accessed 06, Aug, 2017.
  3. 3.
    Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794–9. Scholar
  4. 4.
    Fox P, Hudson M, Brown C, Lord S, Gebski V, De Souza P, et al. Markers of systemic inflammation predict survival in patients with advanced renal cell cancer. Br J Cancer. 2013;109(1):147–53. Scholar
  5. 5.
    Teishima J, Kobatake K, Shinmei S, Inoue S, Hayashi T, Ohara S, et al. The effect of kinetics of C-reactive protein in the prediction of overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor. Urol Oncol. 2017;35(11):662.e1–e7. Scholar
  6. 6.
    Tsimafeyeu IV, Demidov LV, Madzhuga AV, Somonova OV, Yelizarova AL. Hypercoagulability as a prognostic factor for survival in patients with metastatic renal cell carcinoma. J Exp Clin Cancer Res. 2009;28:30. Scholar
  7. 7.
    Cai W, Kong W, Dong B, Zhang J, Chen Y, Xue W, et al. Pretreatment serum prealbumin as an independent prognostic indicator in patients with metastatic renal cell carcinoma using tyrosine kinase inhibitors as first-line target therapy. Clin Genitourin Cancer. 2017;15(3):e437–46. Scholar
  8. 8.
    Ishihara H, Kondo T, Omae K, Takagi T, Iizuka J, Kobayashi H, et al. Sarcopenia and the modified glasgow prognostic score are significant predictors of survival among patients with metastatic renal cell carcinoma who are receiving first-line sunitinib treatment. Target Oncol. 2016;11(5):605–17. Scholar
  9. 9.
    Vavricka SR, Burri E, Beglinger C, Degen L, Manz M. Serum protein electrophoresis: an underused but very useful test. Digestion. 2009;79(4):203–10. Scholar
  10. 10.
    O’Connell TX, Horita TJ, Kasravi B. Understanding and interpreting serum protein electrophoresis. Am Fam Phys. 2005;71(1):105–12.Google Scholar
  11. 11.
    McClatchey KD. Clinical laboratory medicine. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2001.Google Scholar
  12. 12.
    Qu X, Pang Z, Yi W, Wang Y, Wang K, Liu Q, et al. High percentage of alpha1-globulin in serum protein is associated with unfavorable prognosis in non-small cell lung cancer. Med Oncol. 2014;31(10):238. Scholar
  13. 13.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47. Scholar
  14. 14.
    Williamson MA, Michael Snyder L. Wallach’s interpretation of diagnostic tests: pathways to arriving at a clinical diagnosis. Philadelphia: Wolters Kluwer; 2015.Google Scholar
  15. 15.
    Burtis CA, Ashwood ER, Bruns DE. TIETZ textbook of clinical chemistry and molecular diagnostics. St. Louis: Elsevier Saunders; 2006.Google Scholar
  16. 16.
    McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab care. 2009;12(3):223–6. Scholar
  17. 17.
    Moore MM, Chua W, Charles KA, Clarke SJ. Inflammation and cancer: causes and consequences. Clin Pharmacol Ther. 2010;87(4):504–8. Scholar
  18. 18.
    Sun Z, Yang P. Role of imbalance between neutrophil elastase and alpha 1-antitrypsin in cancer development and progression. Lancet Oncol. 2004;5(3):182–90. Scholar
  19. 19.
    Cohen C, McCue PA, Derose PB. Histogenesis of renal cell carcinoma and renal oncocytoma. An immunohistochemical study. Cancer. 1988;62(9):1946–51.CrossRefGoogle Scholar
  20. 20.
    Fleming S, Gibson AA. Proteinase inhibitors in the kidney and its tumours. Histopathology. 1986;10(12):1303–13.CrossRefGoogle Scholar
  21. 21.
    Hwa JS, Park HJ, Jung JH, Kam SC, Park HC, Kim CW, et al. Identification of proteins differentially expressed in the conventional renal cell carcinoma by proteomic analysis. J Korean Med Sci. 2005;20(3):450–5. Scholar
  22. 22.
    Ljungberg B, Grankvist K, Rasmuson T. Serum acute phase reactants and prognosis in renal cell carcinoma. Cancer. 1995;76(8):1435–9.CrossRefGoogle Scholar
  23. 23.
    Shakya R, Tarulli GA, Sheng L, Lokman NA, Ricciardelli C, Pishas KI, et al. Mutant p53 upregulates alpha-1 antitrypsin expression and promotes invasion in lung cancer. Oncogene. 2017;36(31):4469–80. Scholar
  24. 24.
    Chang YH, Lee SH, Liao IC, Huang SH, Cheng HC, Liao PC. Secretomic analysis identifies alpha-1 antitrypsin (A1AT) as a required protein in cancer cell migration, invasion, and pericellular fibronectin assembly for facilitating lung colonization of lung adenocarcinoma cells. Mol Cell Proteomics. 2012;11(11):1320–39. Scholar
  25. 25.
    Li Y, Miao L, Yu M, Shi M, Wang Y, Yang J, et al. alpha1-antitrypsin promotes lung adenocarcinoma metastasis through upregulating fibronectin expression. Int J Oncol. 2017;50(6):1955–64. Scholar
  26. 26.
    Kwon CH, Park HJ, Choi JH, Lee JR, Kim HK, Jo HJ, et al. Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer. Oncotarget. 2015;6(24):20312–26. Scholar
  27. 27.
    Guttman O, Baranovski BM, Schuster R, Kaner Z, Freixo-Lima GS, Bahar N, et al. Acute-phase protein alpha1-anti-trypsin: diverting injurious innate and adaptive immune responses from non-authentic threats. Clin Exp Immunol. 2015;179(2):161–72. Scholar
  28. 28.
    Wahlgren T, Harmenberg U, Sandstrom P, Lundstam S, Kowalski J, Jakobsson M, et al. Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000–2008). Br J Cancer. 2013;108(7):1541–9. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Urology, Zhongshan HospitalFudan UniversityShanghaiChina
  2. 2.Department of Urology, Ren Ji Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina

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