Clinical and Prognostic Significance of Serum Transforming Growth Factor-beta1 Levels in Patients with Pancreatic Ductal Adenocarcinoma

Overview

Journal Braz J Med Biol Res

Specialties Biology
General Medicine

Date 2016 Jul 28

PMID 27464025

Citations 20

Authors

J Zhao

Y Liang

Q Yin

S Liu

Q Wang

Y Tang

C Cao

Affiliations

Soon will be listed here.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate of 5%. Biomarkers for the early detection of pancreatic cancer are urgently needed. Transforming growth factor-beta1 (TGF-β1) is elevated in the tissues and plasma of patients with PDAC. However, no studies systemically report prognostic significance of plasma TGF-β1 levels in PDAC. In the present study, we assessed the prognostic significance of serum TGF-β levels in patients with PDAC. TGF-β levels were determined in serum from 146 PDAC patients, and 58 patients with benign pancreatic conditions. Regression models were used to correlate TGF-β levels to gender, age, stage, class, and metastasis. Survival analyses were performed using multivariate Cox models. Serum levels of TGF-β1 distinguished PDAC from benign pancreatic conditions (P<0.001) and healthy control subjects (P<0.001). Serum levels of TGF-β also distinguished tumor stage (P=0.002) and lymph node metastasis (P=0.001). High serum levels of TGF-β1 were significantly correlated with reduced patient survival. Multivariate analysis revealed that TGF-β1, lymph node metastasis and tumor stage were independent factors for PDAC survival. Our results indicate that serum TGF-β1 may be used as a potential prognostic marker for PDAC.

Citing Articles

The Oncoprotein Mucin 1 in Pancreatic Cancer Onset and Progression: Potential Clinical Implications.

Dieli R, Lioy R, Crispo F, Cascelli N, Martinelli M, Lerose R Biomolecules. 2025; 15(2).

PMID: 40001578 PMC: 11853026. DOI: 10.3390/biom15020275.

The Past, Present, and Future of Biomarkers for the Early Diagnosis of Pancreatic Cancer.

Vitale F, Zileri Dal Verme L, Paratore M, Negri M, Nista E, Ainora M Biomedicines. 2025; 12(12.

PMID: 39767746 PMC: 11673965. DOI: 10.3390/biomedicines12122840.

Atrial fibrillation in cancer, anticancer therapies, and underlying mechanisms.

Shaaban A, Scott S, Greenlee A, Binda N, Noor A, Webb A J Mol Cell Cardiol. 2024; 194:118-132.

PMID: 38897563 PMC: 11500699. DOI: 10.1016/j.yjmcc.2024.06.005.

Role of Elevated Serum TGF-β1 and the Common Promoter -509C/T Polymorphism in the Development and Progression of Primary Glial Tumors and Brain Metastases.

Aleksandrova E, Mindov I, Petrov B, Dimitrova I, Petrov N, Ananiev J Medicina (Kaunas). 2024; 60(1).

PMID: 38256406 PMC: 10819302. DOI: 10.3390/medicina60010146.

Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer.

Hung H, Fan M, Wang D, Miao C, Su P, Liu C BMC Med. 2023; 21(1):338.

PMID: 37667257 PMC: 10478223. DOI: 10.1186/s12916-023-03053-9.

References

Rosado E, Schwartz Z, Sylvia V, Dean D, Boyan B . Transforming growth factor-beta1 regulation of growth zone chondrocytes is mediated by multiple interacting pathways. Biochim Biophys Acta. 2002; 1590(1-3):1-15. DOI: 10.1016/s0167-4889(02)00194-5. View

Kim J, Lee K, Lee J, Paik S, Rhee J, Choi K . Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol. 2004; 19(2):182-6. DOI: 10.1111/j.1440-1746.2004.03219.x. View

Gong Z, Holly E, Bracci P . Survival in population-based pancreatic cancer patients: San Francisco Bay area, 1995-1999. Am J Epidemiol. 2011; 174(12):1373-81. PMC: 3276299. DOI: 10.1093/aje/kwr267. View

Tas F, Tilgen Yasasever C, Karabulut S, Tastekin D, Duranyildiz D . Serum transforming growth factor-beta1 levels may have predictive and prognostic roles in patients with gastric cancer. Tumour Biol. 2014; 36(3):2097-103. DOI: 10.1007/s13277-014-2817-9. View

Massague J . TGFbeta in Cancer. Cell. 2008; 134(2):215-30. PMC: 3512574. DOI: 10.1016/j.cell.2008.07.001. View

Sergeant G, van Eijsden R, Roskams T, Van Duppen V, Topal B . Pancreatic cancer circulating tumour cells express a cell motility gene signature that predicts survival after surgery. BMC Cancer. 2012; 12:527. PMC: 3599097. DOI: 10.1186/1471-2407-12-527. View

Hidalgo M . Pancreatic cancer. N Engl J Med. 2010; 362(17):1605-17. DOI: 10.1056/NEJMra0901557. View

Sultana A, Cox T, Ghaneh P, Neoptolemos J . Adjuvant therapy for pancreatic cancer. Recent Results Cancer Res. 2012; 196:65-88. DOI: 10.1007/978-3-642-31629-6_5. View

Del Pozo Martin Y, Park D, Ramachandran A, Ombrato L, Calvo F, Chakravarty P . Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization. Cell Rep. 2015; 13(11):2456-2469. PMC: 4695340. DOI: 10.1016/j.celrep.2015.11.025. View

10.

Bartscht T, Lehnert H, Gieseler F, Ungefroren H . The Src family kinase inhibitors PP2 and PP1 effectively block TGF-beta1-induced cell migration and invasion in both established and primary carcinoma cells. Cancer Chemother Pharmacol. 2012; 70(2):221-30. DOI: 10.1007/s00280-012-1904-0. View

11.

Petanidis S, Kioseoglou E, Domvri K, Zarogoulidis P, Carthy J, Anestakis D . In vitro and ex vivo vanadium antitumor activity in (TGF-β)-induced EMT. Synergistic activity with carboplatin and correlation with tumor metastasis in cancer patients. Int J Biochem Cell Biol. 2016; 74:121-34. DOI: 10.1016/j.biocel.2016.02.015. View

12.

Plaks V, Kong N, Werb Z . The cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells?. Cell Stem Cell. 2015; 16(3):225-38. PMC: 4355577. DOI: 10.1016/j.stem.2015.02.015. View

13.

Birdsall H, Green D, Trial J, Youker K, Burns A, Mackay C . Complement C5a, TGF-beta 1, and MCP-1, in sequence, induce migration of monocytes into ischemic canine myocardium within the first one to five hours after reperfusion. Circulation. 1997; 95(3):684-92. DOI: 10.1161/01.cir.95.3.684. View

14.

Tascilar M, Skinner H, Rosty C, Sohn T, Wilentz R, Offerhaus G . The SMAD4 protein and prognosis of pancreatic ductal adenocarcinoma. Clin Cancer Res. 2001; 7(12):4115-21. View

15.

Zhao H, Li Y, Feng R, Yu J, Li J, Zhang Y . TGF-β/Smad2/3 signal pathway involves in U251 cell proliferation and apoptosis. Gene. 2015; 562(1):76-82. DOI: 10.1016/j.gene.2015.02.049. View

16.

Lin Y, Kikuchi S, Obata Y, Yagyu K . Serum levels of transforming growth factor beta1 are significantly correlated with venous invasion in patients with gastric cancer. J Gastroenterol Hepatol. 2006; 21(2):432-7. DOI: 10.1111/j.1440-1746.2005.03939.x. View

17.

Tas F, Karabulut S, Tilgen Yasasever C, Duranyildiz D . Serum transforming growth factor-beta 1 (TGF-β1) levels have diagnostic, predictive, and possible prognostic roles in patients with melanoma. Tumour Biol. 2014; 35(7):7233-7. DOI: 10.1007/s13277-014-1984-z. View

18.

Rodriguez T, Saldias A, Irigo M, Zamora J, Perone M, Dewey R . Effect of TGF-β1 Stimulation on the Secretome of Human Adipose-Derived Mesenchymal Stromal Cells. Stem Cells Transl Med. 2015; 4(8):894-8. PMC: 4511148. DOI: 10.5966/sctm.2015-0012. View

19.

Xu S, Yang S, Sun G, Huang W, Zhang Y . Transforming growth factor-beta polymorphisms and serum level in the development of osteosarcoma. DNA Cell Biol. 2014; 33(11):802-6. DOI: 10.1089/dna.2014.2527. View

20.

Kajdaniuk D, Marek B, Borgiel-Marek H, Kos-Kudla B . Transforming growth factor β1 (TGFβ1) in physiology and pathology. Endokrynol Pol. 2013; 64(5):384-96. DOI: 10.5603/EP.2013.0022. View