Co-expression of parathyroid hormone related protein and TGF-beta in breast cancer predicts poor survival outcomeReportar como inadecuado




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BMC Cancer

, 15:925

First Online: 23 November 2015Received: 20 May 2015Accepted: 30 October 2015DOI: 10.1186-s12885-015-1873-x

Cite this article as: Xu, C., Wang, Z., Cui, R. et al. BMC Cancer 2015 15: 925. doi:10.1186-s12885-015-1873-x

Abstract

BackgroundBetter methods to predict prognosis can play a supplementary role in administering individualized treatment for breast cancer patients. Altered expressions of PTHrP and TGF-β have been observed in various types of human cancers. The objective of the current study was to evaluate the association of PTHrP and TGF-β level with the clinicopathological features of the breast cancer patients.

MethodsImmunohistochemistry was used to examine PTHrP and TGF-β protein expression in 497 cases of early breast cancer, and Kaplan-Meier method and COX’s Proportional Hazard Model were applied to the prognostic value of PTHrP and TGF-β expression.

ResultsBoth over-expressed TGF-β and PTHrP were correlated with the tumor in larger size, higher proportion of axillary lymph node metastasis and later clinical stage. Additionally, the tumors with a high TGF-β level developed poor differentiation, and only TGF-β expression was associated with disease-free survival DFS of the breast cancer patients. Followed up for a median of 48 months, it was found that only the patients with negative TGF-β expression had longer DFS P < 0.05, log-rank test. Nevertheless, those with higher PTHrP expression tended to show a higher rate of bone metastasis 67.6 % vs. 45.8 %, P = 0.019. In ER negative subgroup, those who developed PTHrP positive expression presented poor prognosis P < 0.05, log-rank test. The patients with both positive TGF-β and PTHrP expression were significantly associated with the high risk of metastases. As indicated by Cox’s regression analysis, TGF-β expression and the high proportion of axillary lymph node metastasis served as significant independent predictors for breast cancer recurrence.

ConclusionsTGF-β and PTHrP were confirmed to be involved in regulating the malignant progression in breast cancer, and PTHrP expression, to be associated with bone metastasis as a potential prognostic marker in ER negative breast cancer.

KeywordsBreast cancer TGF-β PTHrP Prognosis Survival analysis AbbreviationsAJCCAmerican Joint Committee on Cancer

DFSdisease-free survival

EGFepidermal growth factor

EMTepithelial-mesenchymal transition

ERestrogen receptor

MAHmalignancy-associated hypercalcemia

OPGosteoprotegerin

PDGFplatelet-derived growth factor

PTHparathyroid hormone

PTHrPparathyroid hormone related protein

RANKLreceptor activator for nuclear factor-κ B ligand

RFIrelapse-free interval

TMAstissue microarrays

VEGFvascular endothelial growth factor

Cheng Xu and Zhengyuan Wang contributed equally to this work.

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Autor: Cheng Xu - Zhengyuan Wang - Rongrong Cui - Hongyu He - Xiaoyan Lin - Yuan Sheng - Hongwei Zhang

Fuente: https://link.springer.com/







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