title: Transforming growth factor-β, insulin-like growth factor I/insulin-like growth factor I receptor and vascular endothelial growth factor-A: prognostic and predictive markers in triple-negative and non-triple-negative breast cancer.
abstract: In the current study, the prognostic and predictive values of serum transforming growth factor-β1 (TGF-β1), insulin-like growth factor I (IGF-I)/IGF-I receptor (IGF-IR) and vascular endothelial growth factor-A (VEGF-A) were evaluated in triple-negative and non-triple-negative breast cancer (TNBC and non-TNBC). The aim was to identify a group of serological biomarkers and to identify possible candidates for targeted therapy in patients with TNBC and non-TNBC. Protein levels of TGF-β1, IGF-I/IGF-IR and VEGF-A in the serum were measured in 43 TNBC, 53 non‑TNBC and 20 normal control participants using quantitative ELISA assays. Results were correlated against standard prognostic factors, response to treatment and survival. TNBC was identified to be associated with poor prognosis and serum levels of VEGF-A and IGF/IGF-IR were significantly higher in the TNBC group compared with the non-TNBC group. IGF-IR and VEGF-A overexpression was observed to be correlated with TGF-β1 expression and all of the markers investigated were associated with metastasis and disease progression. In the multivariate analysis, VEGF-A, IGF-I and IGF-IR were observed to be independent predictors for overall survival, whereas TGF-β1 and lymph node status were identified as independent predictors for disease-free survival. The overall response rate was significantly lower in patients with TNBC and those with high levels of TGF-β1, IGF-I/IGF-IR and VEGF-A. In view of the present results, it was concluded that TGF-β1, IGF-I/IGF-IR and VEGF-A overexpression is associated with the presence of aggressive tumors, which exhibit an increased probability of metastasis, a poor response to treatment and reduced survival rate. This indicates that VEGF-A, IGF-IR and IGF-I have the potential to be used as surrogate biomarkers and are promising candidates for targeted therapy, particularly in patients with TNBC.
authors.affiliation: Molecular Pathology Unit, Pathology Department, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Abeer
authors.initials: A
authors.lastname: Bahhnassy
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Misr University for Science and Technology, Cairo 11796, Egypt.
authors.forename: Marwa
authors.initials: M
authors.lastname: Mohanad
authors.affiliation: Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Sabry
authors.initials: S
authors.lastname: Shaarawy
authors.affiliation: Faculty of Pharmacy, Cairo University, Cairo 11796, Egypt.
authors.forename: Manal F
authors.initials: MF
authors.lastname: Ismail
authors.affiliation: Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Bastawisy
authors.affiliation: Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Ashmawy
authors.affiliation: Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11796, Egypt.
authors.forename: Abdel-Rahman
authors.initials: AR
authors.lastname: Zekri
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood*; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000097:blood*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000097:blood*; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D015251:Epirubicin; D007334:Insulin-Like Growth Factor I; D003520:Cyclophosphamide; D017526:Receptor, IGF Type 1; D005472:Fluorouracil
references.citation: Int J Cancer. 1996 Mar 15;65(6):812-20
references.pmid: 8631597
references.citation: Cancer Res. 1992 Dec 15;52(24):6949-52
references.pmid: 1458485
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13909-14
references.pmid: 16172383
references.citation: Br J Cancer. 2001 Aug 3;85(3):422-7
references.pmid: 11487275
references.citation: Clin Cancer Res. 2000 Aug;6(8):3147-52
references.pmid: 10955796
references.citation: Ann N Y Acad Sci. 2002 Jun;963:140-3
references.pmid: 12095938
references.citation: Cancer Res. 1997 Nov 1;57(21):4667-72
references.pmid: 9354418
references.citation: Adv Exp Med Biol. 2008;617:161-9
references.pmid: 18497040
references.citation: J Biol Chem. 2003 Jan 31;278(5):3275-85
references.pmid: 12421823
references.citation: Int J Biol Markers. 2012 Jan-Mar;27(1):53-9
references.pmid: 22020368
references.citation: Mol Cancer Ther. 2007 Oct;6(10):2609-17
references.pmid: 17938257
references.citation: J Cell Biochem Suppl. 2001;Suppl 36:232-46
references.pmid: 11455588
references.citation: PLoS One. 2013;8(2):e56836
references.pmid: 23418605
references.citation: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references.pmid: 10655437
references.citation: Breast Cancer Res Treat. 2009 Jun;115(3):453-95
references.pmid: 18841463
references.citation: BMC Cancer. 2007;7:136
references.pmid: 17651480
references.citation: Microbes Infect. 1999 Dec;1(15):1327-47
references.pmid: 10611761
references.citation: Mol Cell Endocrinol. 2006 Jun 27;252(1-2):241-6
references.pmid: 16647191
references.citation: Cancer Surv. 1992;12:81-103
references.pmid: 1638549
references.citation: Br J Cancer. 2010 Jul 13;103(2):249-55
references.pmid: 20551954
references.citation: Breast Cancer Res Treat. 2008 Nov;112(2):335-41
references.pmid: 18075785
references.citation: J Natl Cancer Inst. 1999 Nov 3;91(21):1829-46
references.pmid: 10547390
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8418-23
references.pmid: 12829800
references.citation: Cancer Res. 2000 Jun 1;60(11):2898-905
references.pmid: 10850435
references.citation: J Clin Oncol. 2008 May 20;26(15):2568-81
references.pmid: 18487574
references.citation: J Clin Oncol. 2008 Mar 10;26(8):1275-81
references.pmid: 18250347
references.citation: Clin Cancer Res. 2011 Apr 15;17(8):2314-27
references.pmid: 21177763
references.citation: Eur J Cancer. 2003 Mar;39(4):454-61
references.pmid: 12751375
references.citation: Clin Biochem. 2009 Sep;42(13-14):1420-6
references.pmid: 19576877
references.citation: Am J Clin Oncol. 1982 Dec;5(6):649-55
references.pmid: 7165009
references.citation: Cancer Res. 2001 Jul 15;61(14):5407-14
references.pmid: 11454684
references.citation: Breast Cancer Res Treat. 2007 Sep;105(1):55-61
references.pmid: 17066319
references.citation: Hum Pathol. 2004 Dec;35(12):1537-42
references.pmid: 15619214
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15593-8
references.pmid: 16230630
references.citation: J Clin Invest. 2003 Oct;112(7):1116-24
references.pmid: 14523048
references.citation: Clin Cancer Res. 2003 Apr;9(4):1253-8
references.pmid: 12684392
references.citation: Cancer Cell. 2007 Mar;11(3):259-73
references.pmid: 17349583
references.citation: Breast. 2011 Oct;20 Suppl 3:S135-41
references.pmid: 22015281
references.citation: Breast Cancer Res Treat. 1999 Jul;56(1):1-10
references.pmid: 10517338
references.citation: Arch Surg. 2001 Aug;136(8):937-40
references.pmid: 11485532
references.citation: Clin Cancer Res. 2003 Oct 15;9(13):4722-9
references.pmid: 14581342
references.citation: Oncogene. 2000 May 18;19(22):2687-94
references.pmid: 10851068
references.citation: Int J Cancer. 1997 Oct 21;74(5):492-501
references.pmid: 9355970
references.citation: Lab Invest. 1995 Sep;73(3):311-31
references.pmid: 7564264
references.citation: J Biol Chem. 2000 Aug 18;275(33):25451-9
references.pmid: 10846175
references.citation: Br J Cancer. 2006 Jan 30;94(2):239-46
references.pmid: 16404434
references.citation: Int J Womens Health. 2012;4:511-20
references.pmid: 23071421
references.citation: Eur J Clin Invest. 2008 Jun;38(6):438-46
references.pmid: 18452545
references.citation: Nat Rev Cancer. 2004 Jul;4(7):505-18
references.pmid: 15229476
references.citation: J Biol Chem. 1999 Apr 30;274(18):12423-30
references.pmid: 10212216
references.citation: CA Cancer J Clin. 2011 Jul-Aug;61(4):212-36
references.pmid: 21685461
references.citation: Indian J Pharmacol. 2011 May;43(3):236-45
references.pmid: 21713084
references.citation: Breast Cancer (Auckl). 2011;5:175-99
references.pmid: 21863131
references.citation: Clin Cancer Res. 2007 Aug 1;13(15 Pt 1):4429-34
references.pmid: 17671126
references.citation: J Clin Invest. 1999 Jan;103(2):197-206
references.pmid: 9916131
references.citation: Cancer J. 2010 Jan-Feb;16(1):33-8
references.pmid: 20164688
references.citation: Oncology. 2002;63(4):317-32
references.pmid: 12417786