全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS ONE  2014 

Serum Inhibin A and Inhibin B Levels in Epithelial Ovarian Cancer Patients

DOI: 10.1371/journal.pone.0090575

Full-Text   Cite this paper   Add to My Lib

Abstract:

The aim of our study was to examine serum inhibin A and inhibin B concentrations in ovarian cancer patients in relation to clinicopathological features and 5-year survival. Material and Methods We enrolled 90 epithelial ovarian cancer patients in our study, aged 45–81 years, who underwent optimal cytoreductive surgery. In all patients, serum inhibin A and inhibin B concentrations were measured using a two-step sandwich type enzyme immunoassay before surgery. Results In the group of patients with ovarian cancer median serum concentration of inhibin A was 3.87 pg/mL (0.96–10.09) and inhibin B was 13.9 pg/mL (5.1–45.0). Median concentrations of inhibin A and B in relation to FIGO stage and histological subtype did not differ significantly. Inhibin A levels were significantly higher in patients with lower grading (G1 and G2) in comparison to those with higher grade G3 (p = 0.001). There were no differences in inhibin B concentrations in relation to grading. The Kaplan-Meier analyses demonstrated no differences in survival rate in relation to inhibin A levels, while there was a stepwise impairment of 5-years survival with increased inhibin B level. In the group of patients with inhibin B levels higher than 20 pg/ml the survival rate was lower (p = 0,00625, log-rank test). Conclusion 1. Higher inhibin A serum levels were found in patients with highly differentiated ovarian carcinoma compared to the group of patients with a poorly differentiated cancer, which may confirm the influence of inhibin A on cell proliferation processes. 2. A significant importance of inhibin B was demonstrated in the prediction of death within less than a five year period. The probability of survival in patients featuring high inhibin B levels was lower with statistical significance. This may indicate the need for further studies on how to block the inhibin B activation pathway in the ovarian carcinoma therapy.

References

[1]  Siegel R, Naishadham D, Jemal A (2012) Cancer statistics. CA Cancer J Clin 62: 10–29. doi: 10.3322/caac.20138
[2]  Pfeiffer RM, Park Y, Kreimer AR, Lacey JV Jr, Pee D, et al. (2013) Risk Prediction for Breast, Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies. PLoS Med 10(7): e1001492 doi:10.1371/journal.pmed.1001492.
[3]  Park Y, Lee JH, Hong DJ, Lee EY, Kim HS (2011) Diagnostic performances of HE4 and CA125 for the detection of ovarian cancer from patients with various gynecologic and non-gynecologic diseases. Clin Biochem 44: 884–8. doi: 10.1016/j.clinbiochem.2011.04.011
[4]  Walentowicz-Sadlecka M, Grabiec M, Sadlecki P, Gotowska M, Walentowicz P, et al. (2012) 25(OH)D3 in patients with ovarian cancer and its correlation with survival. Clin Biochem 45: 1568–72. doi: 10.1016/j.clinbiochem.2012.07.110
[5]  Zhang W, Ota T, Shridhar V, Chien J, Wu B, et al. (2013) Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment. PLoS Comput Biol 9(3): e1002975 doi:10.1371/journal.pcbi.1002975.
[6]  Leversha LJ, Robertson DM, de Vos FL, Morgan FJ, Hearn MT, et al. (1987) Isolation of inhibin from ovine follicular fluid. J Endocrinol 113(2): 213–21. doi: 10.1677/joe.0.1130213
[7]  Stenvers KL, Findlay JK (2012) Inhibins and activins: towards the future. A tribute to the late Professor Wylie W. Vale. Mol Cell Endocrinol 359(1–2): 1. doi: 10.1016/j.mce.2012.03.001
[8]  Mason AJ, Farnworth PG, Sullivan J (1996) Characterization and determination of the biological activities of noncleavable high molecular weight forms of inhibin A and activin A. Mol Endocrinol 10(9): 1055–65. doi: 10.1210/mend.10.9.8885240
[9]  Walton KL, Makanji Y, Harrison CA (2012) New insights into the mechanisms of activin action and inhibition. Mol Cell Endocrinol 359(1–2): 2–12 doi:10.1016/j.mce.2011.06.030.
[10]  Makanji Y, Walton KL, Wilce MC, Chan KL, Robertson DM, et al. (2008) Suppression of inhibin A biological activity by alterations in the binding site for betaglycan. J Biol Chem 283(24): 16743–51 doi:10.1074/jbc.M801045200.
[11]  Antenos M, Stemler M, Boime I, Woodruff TK (2007) N-linked oligosaccharides direct the differential assembly and secretion of inhibin alpha- and betaA-subunit dimers. Mol Endocrinol 21(7): 1670–84. doi: 10.1210/me.2007-0050
[12]  Makanji Y, Harrison CA, Robertson DM (2011) Feedback regulation by inhibins A and B of the pituitary secretion of follicle-stimulating hormone. Vitam Horm 85: 299–321 doi:10.1016/B978-0-12-385961-7.00014-7.
[13]  Lewis KA, Gray PC, Blount AL, MacConell LA, Wiater E, et al. (2000) Betaglycan binds inhibin and can mediate functional antagonism of activin signalling. Nature 404(6776): 411–4. doi: 10.1038/35006129
[14]  Cheifetz S, Ling N, Guillemin R, Massagué J (1988) A surface component on GH3 pituitary cells that recognizes transforming growth factor-beta, activin, and inhibin. J Biol Chem 263(33): 17225–8.
[15]  Findlay JK, Risbridger GP (1987) Intragonadal control mechanisms. Baillieres Clin Endocrinol Metab 1: 223–243. doi: 10.1016/s0950-351x(87)80060-5
[16]  Sharma A, Burnell M, Gentry-Maharaj A, Campbell S, Amso NN, et al. (2013) United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Factors affecting visualization of postmenopausal ovaries: descriptive study from the multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Ultrasound Obstet Gynecol 42(4): 472–7 doi:10.1002/uog.12447.
[17]  Robertson DM, Hale GE, Jolley D, Fraser IS, Hughes CL, et al. (2009) Interrelationships between ovarian and pituitary hormones in ovulatory menstrual cycles across reproductive age. J Clin Endocrinol Metab 94: 138–144. doi: 10.1210/jc.2008-1684
[18]  Knight PG, Glister C (2006) TGF-b superfamily members and ovarian follicle development. Reproduction 132: 191–206. doi: 10.1530/rep.1.01074
[19]  Gatza CE, Oh SY, Blobe GC (2010) Roles for the type III TGF-beta receptor in human cancer. Cell Signal 22: 1163–74 doi:10.1016/j.cellsig.2010.01.016.
[20]  Wiater E, Lewis KA, Donaldson C, Vaughan J, Bilezikjian L, et al. (2009) Endogenous betaglycan is essential for high-potency inhibin antagonism in gonadotropes. Mol Endocrinol 23: 1033–42. doi: 10.1210/me.2009-0021
[21]  Makanji Y, Harrison CA, Stanton PG, Krishna R, Robertson DM (2007) Inhibin A and B in vitro bioactivities are modified by their degree of glycosylation and their affinities to betaglycan. Endocrinology 148(5): 2309–16. doi: 10.1210/en.2006-1612
[22]  Makanji Y, Temple-Smith PD, Walton KL, Harrison CA, Robertson DM (2009) Inhibin B is a more potent suppressor of rat follicle-stimulating hormone release than inhibin a in vitro and in vivo. Endocrinology 150: 4784–93. doi: 10.1210/en.2008-1783
[23]  Farnworth PG, Stanton PG, Wang Y, Escalona R, Findlay JK, et al. (2006) Inhibins differentially antagonize activin and bone morphogenetic protein action in a mouse adrenocortical cell line. Endocrinology 147: 3462–71. doi: 10.1210/en.2006-0023
[24]  Baud V, Karin M (2009) Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls. Nat Rev Drug Discov 8: 33–40 doi:10.1038/nrd2781.
[25]  Deregowski V, Delhalle S, Benoit V, Bours V, Merville MP (2002) Identification of cytokine-induced nuclear factor-kappaB target genes in ovarian and breast cancer cells. Biochem Pharmacol 64: 873–81. doi: 10.1016/s0006-2952(02)01151-6
[26]  Bonome T, Levine DA, Shih J, Randonovich M, Pise-Masison CA, et al. (2008) A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer. Cancer Res 68: 5478–86 doi:10.1158/0008-5472.CAN-07-6595.
[27]  Hernandez L, Hsu SC, Davidson B, Birrer MJ, Kohn EC, et al. (2010) Activation of NF-kappaB signaling by inhibitor of NF-kappaB kinase beta increases aggressiveness of ovarian cancer. Cancer Res 70: 4005–14 doi:10.1158/0008-5472.CAN-09-3912.
[28]  Hirschhorn T, Barizilay L, Smorodinsky NI, Ehrlich M (2012) Differential regulation of Smad3 and of the type II transforming growth factor-β receptor in mitosis: implications for signaling. PLoS One 7(8): e43459 doi:10.1371/journal.pone.0043459.
[29]  Quartuccio SM, Lantvit DD, Bosland MC, Burdette JE (2013) Conditional inactivation of p53 in mouse ovarian surface epithelium does not alter MIS driven Smad2-dominant negative epithelium-lined inclusion cysts or teratomas. PLoS One 8(5): e65067 doi:10.1371/journal.pone.0065067.
[30]  Kisielewski R, To?wińska A, Mazurek A, Laudański P (2013) Inflammation and ovarian cancer–current views. Ginekol Pol 84(4): 293–7.
[31]  Thériault BL, Nachtigal MW (2011) Human ovarian cancer cell morphology, motility, and proliferation are differentially influenced by autocrine TGFβ superfamily signalling. Cancer Lett 313(1): 108–21 doi:10.1016/j.canlet.2011.08.033.
[32]  Son DS, Kabir SM, Dong YL, Lee E, Adunyah SE (2012) Inhibitory effect of tumor suppressor p53 on proinflammatory chemokine expression in ovarian cancer cells by reducing proteasomal degradation of IκB. PLoS One 7(12): e51116 doi:10.1371/journal.pone.0051116.
[33]  Zhao BX, Sun YB, Wang SQ, Duan L, Huo QL, et al. (2013) Grape Seed Procyanidin Reversal of P-glycoprotein Associated Multi-Drug Resistance via Down-regulation of NF-κB and MAPK/ERK Mediated YB-1 Activity in A2780/T Cells. PLoS One 8(8): e71071 doi:10.1371/journal.pone.0071071.
[34]  Delfino KR, Rodriguez-Zas SL (2013) Transcription factor-microRNA-target gene networks associated with ovarian cancer survival and recurrence. PLoS One 8(3): e58608 doi:10.1371/journal.pone.0058608.
[35]  Rachidi SM, Qin T, Sun S, Zheng WJ, Li Z (2013) Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker. PLoS One 8(3): e57911 doi:10.1371/journal.pone.0057911.
[36]  Sohn I, Sung CO (2013) Predictive modeling using a somatic mutational profile in ovarian high grade serous carcinoma. PLoS One 8(1): e54089 doi:10.1371/journal.pone.0054089.
[37]  Tournier I, Marlin R, Walton K, Charbonnier F, Coutant S, et al.. (2013) Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors. Hum Mutat. Dec 2. doi: 10.1002/humu.22489.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133