Elevated Serum FGG Levels Prognosticate and Promote the Disease Progression in Prostate Cancer

Overview

Journal Front Genet

Date 2021 May 17

PMID 33995485

Citations 18

Authors

H H Peng

J N Wang

L F Xiao

M Yan

S P Chen

L Wang

K Yang

Affiliations

Soon will be listed here.

Abstract

Castration-resistant prostate cancer (CRPC) threatens the health of men in general and no effective therapeutics currently exists for the treatment of CRPC. It is therefore of great importance to find a novel molecule that can be a biomarker and a therapeutic target for CRPC. First, we found that the serum fibrinogen gamma (FGG) levels in patients with CRPC were significantly higher than those with localized prostate cancer (PCa) through iTRAQ proteomics and ELISA experiments. Immunohistochemistry, quantitative real-time polymerase chain reaction and western blot also showed an increase of FGG expression in CRPC tissues and cells. Then we proved the proliferation, invasion and migration ability of CRPC cells were significantly reduced after FGG knockdown. The number of apoptotic cells increased at least sixfold after FGG silencing, and was observed in conjunction with an upregulation of p53, caspase 3, clea-caspase 3, and Bax, and a downregulation of Bcl2 and survivin. FGG knockdown in DU145 cells resulted in smaller xenografts than control cells in a mouse model. and we established that FGG is modulated by IL-6 which was increased in CRPC patients via phosphorylation of STAT3. The data suggests that FGG may be a potential therapeutic target and prognostic marker for CRPC.

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References

Attard G, Parker C, Eeles R, Schroder F, Tomlins S, Tannock I . Prostate cancer. Lancet. 2015; 387(10013):70-82. DOI: 10.1016/S0140-6736(14)61947-4. View

Steinbrecher K, Horowitz N, Blevins E, Barney K, Shaw M, Harmel-Laws E . Colitis-associated cancer is dependent on the interplay between the hemostatic and inflammatory systems and supported by integrin alpha(M)beta(2) engagement of fibrinogen. Cancer Res. 2010; 70(7):2634-43. PMC: 4288842. DOI: 10.1158/0008-5472.CAN-09-3465. View

Palumbo J, Kombrinck K, Drew A, Grimes T, Kiser J, Degen J . Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood. 2000; 96(10):3302-9. View

Sahni A, Simpson-Haidaris P, Sahni S, Vaday G, Francis C . Fibrinogen synthesized by cancer cells augments the proliferative effect of fibroblast growth factor-2 (FGF-2). J Thromb Haemost. 2007; 6(1):176-83. DOI: 10.1111/j.1538-7836.2007.02808.x. View

Liu C, Zhu Y, Lou W, Cui Y, Evans C, Gao A . Inhibition of constitutively active Stat3 reverses enzalutamide resistance in LNCaP derivative prostate cancer cells. Prostate. 2013; 74(2):201-9. PMC: 4437226. DOI: 10.1002/pros.22741. View

Shu Y, Weng H, Bao R, Wu X, Ding Q, Cao Y . Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study. BMC Cancer. 2014; 14:566. PMC: 4131047. DOI: 10.1186/1471-2407-14-566. View

Wang Y, Yin W, Wang Z, Huang J, Pan J, Zhu Y . Pretreatment plasma fibrinogen as an independent prognostic indicator of prostate cancer patients treated with androgen deprivation therapy. Prostate Cancer Prostatic Dis. 2016; 19(2):209-15. DOI: 10.1038/pcan.2016.6. View

Yu W, Li J, Wang Q, Wang B, Zhang L, Liu Y . Targeting POH1 inhibits prostate cancer cell growth and enhances the suppressive efficacy of androgen deprivation and docetaxel. Prostate. 2019; 79(11):1304-1315. DOI: 10.1002/pros.23838. View

Pichler M, Hutterer G, Stojakovic T, Mannweiler S, Pummer K, Zigeuner R . High plasma fibrinogen level represents an independent negative prognostic factor regarding cancer-specific, metastasis-free, as well as overall survival in a European cohort of non-metastatic renal cell carcinoma patients. Br J Cancer. 2013; 109(5):1123-9. PMC: 3778296. DOI: 10.1038/bjc.2013.443. View

10.

Balkwill F, Mantovani A . Inflammation and cancer: back to Virchow?. Lancet. 2001; 357(9255):539-45. DOI: 10.1016/S0140-6736(00)04046-0. View

11.

Schroeder A, Herrmann A, Cherryholmes G, Kowolik C, Buettner R, Pal S . Loss of androgen receptor expression promotes a stem-like cell phenotype in prostate cancer through STAT3 signaling. Cancer Res. 2013; 74(4):1227-37. PMC: 4539262. DOI: 10.1158/0008-5472.CAN-13-0594. View

12.

de Las Pozas A, Reiner T, De Cesare V, Trost M, Perez-Stable C . Inhibiting Multiple Deubiquitinases to Reduce Androgen Receptor Expression in Prostate Cancer Cells. Sci Rep. 2018; 8(1):13146. PMC: 6120934. DOI: 10.1038/s41598-018-31567-3. View

13.

Paule B, Terry S, Kheuang L, Soyeux P, Vacherot F, De La Taille A . The NF-kappaB/IL-6 pathway in metastatic androgen-independent prostate cancer: new therapeutic approaches?. World J Urol. 2007; 25(5):477-89. DOI: 10.1007/s00345-007-0175-6. View

14.

Pedrazzani C, Mantovani G, Salvagno G, Baldiotti E, Ruzzenente A, Iacono C . Elevated fibrinogen plasma level is not an independent predictor of poor prognosis in a large cohort of Western patients undergoing surgery for colorectal cancer. World J Gastroenterol. 2016; 22(45):9994-10001. PMC: 5143766. DOI: 10.3748/wjg.v22.i45.9994. View

15.

Thurner E, Krenn-Pilko S, Langsenlehner U, Stojakovic T, Pichler M, Gerger A . The association of an elevated plasma fibrinogen level with cancer-specific and overall survival in prostate cancer patients. World J Urol. 2014; 33(10):1467-73. DOI: 10.1007/s00345-014-1459-2. View

16.

Luo Y, Kim H, Kim M, Lee M, Song Y . Elevated plasma fibrinogen levels and prognosis of epithelial ovarian cancer: a cohort study and meta-analysis. J Gynecol Oncol. 2017; 28(3):e36. PMC: 5391395. DOI: 10.3802/jgo.2017.28.e36. View

17.

Repetto O, De Re V . Coagulation and fibrinolysis in gastric cancer. Ann N Y Acad Sci. 2017; 1404(1):27-48. DOI: 10.1111/nyas.13454. View

18.

Ziaran S, Goncalves F, Breza Sr J . Patients with prostate cancer treated by ADT have significantly higher fibrinogenemia than healthy control. World J Urol. 2012; 31(2):289-92. DOI: 10.1007/s00345-012-0926-x. View

19.

Palumbo J, Degen J . Mechanisms coupling the hemostatic system to colitis-associated cancer. Thromb Res. 2010; 125 Suppl 2:S39-43. DOI: 10.1016/S0049-3848(10)70011-6. View

20.

Perisanidis C, Psyrri A, Cohen E, Engelmann J, Heinze G, Perisanidis B . Prognostic role of pretreatment plasma fibrinogen in patients with solid tumors: A systematic review and meta-analysis. Cancer Treat Rev. 2015; 41(10):960-70. DOI: 10.1016/j.ctrv.2015.10.002. View