Zie ook literatuurlijst niet-toxische middelen, voeding en voedingsstoffen en minder belastende behandelingen specifiek bij nierkanker samengesteld door arts-bioloog drs. Engelbert Valstar.

29 juni 2020: Bron: Targeted Oncology volume 15, pages347–356(2020)

γ-Glutamyltransferase (GGT)  (Gammaglutamyltransferase) is een enzymmarker (eiwitmarker) van zogeheten oxidatieve stress. Verhoogde bloedwaarden van GGT is gekoppeld aan slechte overleving bij verschillende vormen van kanker. Zo ook blijkt dit op te gaan voor patiënten met uitgezaaide gevorderde nierkanker.

Uit een Japanse retrospectieve studie van totaal 156 patiënten met uitgezaaide nierkanker (mRCC) die tussen april 2008 en januari 2019 een eerstelijns- of tweedelijns TKI-therapie kregen, onderzochten de onderzoekers wat de voorspellende rol voor overall overleving is geweest van bloedwaarde γ-Glutamyltransferase (GGT)  en om te onderzoeken of overexpressie van GGT in RCC-cellen heeft bijgedragen tot verhoging van serum GGT met behulp van chirurgisch verwijderde RCC-kankerweefsel.

De mediane overall overleving (OS) was respectievelijk 16,0 maanden en 36,8 maanden bij patiënten met verhoogde GGT-spiegels en zonder verhoogde GGT (P <.001).
Bij een multivariabele analyse was een verhoogde bloed-GGT een onafhankelijke ongunstige prognostische factor (HR, 4,04; P <.001), samen met hoge concentraties neutrofielen (HR, 2,06; P = .041), lage albumine (HR, 2,00, P = 0,006), hoge LDH (HR, 2,68; P <0,001) en hoge De Ritis-ratio (AST/ALT) (HR, 1,97; P = 0,004). 

Het studierapport: Impact of Serum γ-Glutamyltransferase on Overall Survival in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy is tegen betlaing in te zien.

Hier het abstract van de studie: 

Impact of Serum γ-Glutamyltransferase on Overall Survival in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy

Abstract

Background

γ-Glutamyltransferase (GGT) is a marker of oxidative stress. Elevated serum GGT is linked to poor survival in various malignancies; however, there are no data on metastatic renal cell carcinoma (mRCC). Additionally, GGT expression in cancer tissues remains largely unknown.

Objective

The present study was designed to determine the prognostic role of serum GGT in patients with mRCC and the association between systemic and local GGT levels.

Patients and Methods

Pretherapeutic serum GGT and other clinicopathological parameters were retrospectively compared with overall survival (OS) in 146 consecutive patients with mRCC receiving tyrosine kinase inhibitor therapy. GGT expression was analyzed in 65 resected specimens using immunohistochemistry.

Results

A total of 82 patients (56%) died during the follow-up period (median 34.9 months). Median OS was 16.0 months and 36.8 months in patients with elevated GGT levels and without elevated GGT, respectively (P < 0.001). On multivariable analysis, elevated serum GGT was an independent adverse prognostic factor (hazard ratio 4.04, P < 0.001), together with high neutrophils (HR 2.06, P = 0.041), low albumin (HR 2.00, P = 0.006), high lactate dehydrogenase (HR 2.68, P < 0.001), and high De Ritis ratio (HR 1.97, P = 0.004). Preoperative serum GGT levels were 29, 48, and 109 U/l in patients whose renal cancer cells showed negative to weak, moderate, and strong GGT expression, respectively (P = 0.004).

Conclusions

Elevated serum GGT was an unfavorable prognostic factor in mRCC, and overexpression of GGT in renal cancer cells might be responsible for elevation of serum GGT.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Capitanio U, Bensalah K, Bex A, Boorjian SA, Bray F, Coleman J, et al. Epidemiology of renal cell carcinoma. Eur Urol. 2019;75(1):74–84.

    Article Google Scholar 

  2. 2.

    Yuasa T, Masuda H, Yamamoto S, Numao N, Yonese J. Biomarkers to predict prognosis and response to checkpoint inhibitors. Int J Clin Oncol. 2017;22(4):629–34.

    CAS Article Google Scholar 

  3. 3.

    Motzer RJ, Tannir NM, McDermott DF, Arén Frontera O, Melichar B, Choueiri TK, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.

    CAS Article Google Scholar 

  4. 4.

    Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356(2):125–34.

    CAS Article Google Scholar 

  5. 5.

    Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24.

    CAS Article Google Scholar 

  6. 6.

    Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061–8.

    CAS Article Google Scholar 

  7. 7.

    Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931–9.

    CAS Article Google Scholar 

  8. 8.

    Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002;20(1):289–96.

    CAS Article Google Scholar 

  9. 9.

    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.

    CAS Article Google Scholar 

  10. 10.

    Bezan A, Mrsic E, Krieger D, Stojakovic T, Pummer K, Zigeuner R, et al. The preoperative AST/ALT (De Ritis) ratio represents a poor prognostic factor in a cohort of patients with nonmetastatic renal cell carcinoma. J Urol. 2015;194(1):30–5.

    Article Google Scholar 

  11. 11.

    Takagi T, Fukuda H, Kondo T, Ishihara H, Yoshida K, Kobayashi H, et al. Prognostic markers for refined stratification of IMDC intermediate-risk metastatic clear cell renal cell carcinoma treated with first-line tyrosine kinase inhibitor therapy. Target Oncol. 2019;14(2):179–86.

    Article Google Scholar 

  12. 12.

    Santoni M, Buti S, Conti A, Porta C, Procopio G, Sternberg CN, et al. Prognostic significance of host immune status in patients with late relapsing renal cell carcinoma treated with targeted therapy. Target Oncol. 2015;10(4):517–22.

    Article Google Scholar 

  13. 13.

    Saito K, Tatokoro M, Fujii Y, Iimura Y, Koga F, Kawakami S, et al. Impact of C-reactive protein kinetics on survival of patients with metastatic renal cell carcinoma. Eur Urol. 2009;55(5):1145–53.

    CAS Article Google Scholar 

  14. 14.

    Hanigan MH, Frierson HF. Immunohistochemical detection of gamma-glutamyl transpeptidase in normal human tissue. J Histochem Cytochem. 1996;44(10):1101–8.

    CAS Article Google Scholar 

  15. 15.

    Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263–355.

    CAS Article Google Scholar 

  16. 16.

    Takemura K, Fukushima H, Ito M, Kataoka M, Nakanishi Y, Sakamoto K, et al. Prognostic significance of serum γ-glutamyltransferase in patients with advanced urothelial carcinoma. Urol Oncol. 2019;37(2):108–15.

    CAS Article Google Scholar 

  17. 17.

    Takemura K, Ito M, Nakanishi Y, Kataoka M, Sakamoto K, Suzuki H, et al. Serum γ-glutamyltransferase as a prognostic biomarker in metastatic castration-resistant prostate cancer treated with enzalutamide. Anticancer Res. 2019;39(10):5773–800.

    Article Google Scholar 

  18. 18.

    Hofbauer SL, Stangl KI, de Martino M, Lucca I, Haitel A, Shariat SF, et al. Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma. Br J Cancer. 2014;111(8):1526–31.

    CAS Article Google Scholar 

  19. 19.

    Dalpiaz O, Pichler M, Mrsic E, Reitz D, Krieger D, Venturino L, et al. Preoperative serum-gamma-glutamyltransferase (GGT) does not represent an independent prognostic factor in a European cohort of patients with non-metastatic renal cell carcinoma. J Clin Pathol. 2015;68(7):547–51.

    CAS Article Google Scholar 

  20. 20.

    Luo C, Xu B, Fan Y, Yu W, Zhang Q, Jin J. Preoperative gamma-glutamyltransferase is associated with cancer-specific survival and recurrence-free survival of nonmetastatic renal cell carcinoma with venous tumor thrombus. Biomed Res Int. 2017;2017:3142926.

    PubMed PubMed Central Google Scholar 

  21. 21.

    Sandock DS, Seftel AD, Resnick MI. The role of gamma-glutamyl transpeptidase in the preoperative metastatic evaluation of renal cell carcinoma. J Urol. 1997;157(3):798–9.

    CAS Article Google Scholar 

  22. 22.

    Simic T, Dragicevic D, Savic-Radojevic A, Cimbaljevic S, Tulic C, Mimic-Oka J. Serum gamma glutamyl-transferase is a sensitive but unspecific marker of metastatic renal cell carcinoma. Int J Urol. 2007;14(4):289–93.

    CAS Article Google Scholar 

  23. 23.

    Ramankulov A, Lein M, Kristiansen G, Meyer HA, Loening SA, Jung K. Elevated plasma osteopontin as marker for distant metastases and poor survival in patients with renal cell carcinoma. J Cancer Res Clin Oncol. 2007;133(9):643–52.

    CAS Article Google Scholar 

  24. 24.

    Bansal A, Sanchez DJ, Nimgaonkar V, Sanchez D, Riscal R, Skuli N, et al. Gamma-glutamyltransferase 1 promotes clear cell renal cell carcinoma initiation and progression. Mol Cancer Res. 2019;17(9):1881–922.

    CAS Article Google Scholar 

  25. 25.

    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.

    CAS Article Google Scholar 

  26. 26.

    Grimm C, Hofstetter G, Aust S, Mutz-Dehbalaie I, Bruch M, Heinze G, et al. Association of gamma-glutamyltransferase with severity of disease at diagnosis and prognosis of ovarian cancer. Br J Cancer. 2013;109(3):610–4.

    CAS Article Google Scholar 

  27. 27.

    Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6(7):655–63.

    CAS Article Google Scholar 

  28. 28.

    Aalen OO. Further results on the non-parametric linear regression model in survival analysis. Stat Med. 1993;12(17):1569–88.

    CAS Article Google Scholar 

  29. 29.

    Harrell FE, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247(18):2543–6.

    Article Google Scholar 

  30. 30.

    Wang Q, Shu X, Dong Y, Zhou J, Teng R, Shen J, et al. Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular interpretation of an old biomarker in gastric cancer. Oncotarget. 2017;8(22):36171–84.

    Article Google Scholar 

Download references

Author information

Affiliations

Contributions

Each author qualifies for authorship based on substantial contributions. Conception and design: KT, TY, KI, and FK. Acquisition of data: KT, TY, KI, and GA. Analysis and interpretation of data: KT. Drafting of the manuscript: KT. Critical revision of the manuscript for important intellectual content: KT, TY, FK, and PGB. Statistical analysis: KT. Obtaining funding: TY. Administrative, technical, or material support: JY. Supervision: TY and JY. Other: none.

Corresponding author

Correspondence to Kosuke Takemura.

Ethics declarations

Funding

Dr. Yuasa has been funded by the Smoking Research Foundation and JSPS KAKENHI Grant Number 16K11035; however, there was no direct or indirect commercial incentive associated with publishing this article.

Conflict of interest

Kosuke Takemura, Takeshi Yuasa, Kentaro Inamura, Gulanbar Amori, Fumitaka Koga, Philip G. Board, and Junji Yonese declare that they have no conflicts of interest that might be relevant to the contents of this article.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 359 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Takemura, K., Yuasa, T., Inamura, K. et al. Impact of Serum γ-Glutamyltransferase on Overall Survival in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy. Targ Oncol 15, 347–356 (2020). https://doi.org/10.1007/s11523-020-00719-9

Download citation

 


Plaats een reactie ...

Reageer op "Algemeen: Verhoogde bloedwaarden van γ-Glutamyltransferase (GGT) geeft een sterk negatieve prognose op overall overleving, 16 vs 38 maanden), voor patienten met uitgezaaide nierkanker"


Gerelateerde artikelen
 

Gerelateerde artikelen

Waaraan moet een ziekenhuis >> Overzicht van belangrijke >> ESMO 2022: aanbevolen abstracten >> ASCO 2023. Aanbevolen abstracten >> Algemeen: Verhoogde bloedwaarden >> Chemotherapie met gemcitabine >> HIFU - High Focused Ultra >> Immuuntherapie bij nierkanker, >> Interferon Alpha als aanvullende >> Nexavar(R) (sorafenib tosylate) >>