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. 2019 Aug 1;12(8):2920-2930.
eCollection 2019.

The expressions of autotaxin-lysophosphatidate signaling-related proteins in metastatic breast cancer

Su Jung Shim  1 , Eunah Shin  2 , Choong-Sik Lee  3 , Ja Seung Koo  4
Affiliations

The expressions of autotaxin-lysophosphatidate signaling-related proteins in metastatic breast cancer

Su Jung Shim et al. Int J Clin Exp Pathol. .

Abstract

Purpose: We evaluated the expression of autotaxin-lysophosphatidate signaling-related proteins and the clinical implications for metastatic breast cancer.

Methods: We constructed tissue microarrays (TMA) with 126 cases of metastatic breast cancer [31 (24.6%) bone metastases, 36 (28.6%) brain metastases, 11 (8.7%) liver metastases, and 48 (38.1%) lung metastasis], and we conducted immunohistochemical staining for the autotoxin-lysophosphatidate signaling-related proteins ATX, LPA1, LPA2, and LPA3.

Results: Stromal ATX (P = 0.006) and LPA1 (P < 0.001) were differently expressed according to their metastatic organ; stromal ATX showed high expression in bone metastasis, and LPA1 showed high expression in liver and lung metastases. Stromal ATX positivity was higher than others in luminal A type tumors (P = 0.035), and stromal LPA3 positivity was correlated with a high Ki-67 labeling index (LI) (P = 0.005). In univariate analysis, tumoral LPA3 negativity was correlated with shorter overall survival (OS) (P = 0.015) in metastatic breast cancer. When analyzed according to the metastatic sites, tumoral LPA3 negativity was correlated with shorter OS (P = 0.010) in lung metastasis, whereas stromal LPA3 negativity was correlated with shorter OS (P = 0.026) in brain metastasis. In multivariate Cox analysis, tumoral LPA3 negativity was an independent poor prognostic factor (HR = 2.311, 95% CI: 1.029-5.191, P = 0.043).

Conclusion: Among autotoxin-lysophosphatidate signaling-related proteins, stromal ATX was highly expressed in bone metastases, and LPA1 was highly expressed in liver and lung metastases. Tumoral LPA3 might be a prognostic factor in metastatic breast cancer.

Keywords: Autotaxin; breast cancer; lysophosphatidate receptor; metastasis.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Heat map of the expression of autotaxin-lysophosphatidate signaling-related proteins according to the metastatic site in metastatic breast cancer. S, stroma.
Figure 2
Figure 2
Expressions of autotaxin-lysophosphatidate signaling-related proteins according to the metastatic site in metastatic breast cancer. Stromal ATX is highly expressed in bone and lung metastases, and tumoral LPA1 is highly expressed in liver and lung metastases. The insets represent the positive controls.
Figure 3
Figure 3
Western blot for autotaxin-lysophosphatidate signaling-related proteins according to the metastatic site in metastatic breast cancer. Stromal ATX is highly expressed in bone and lung metastases, and tumoral LPA1 is highly expressed in liver and lung metastases.
Figure 4
Figure 4
Correlation between clinicopathologic factors and the expression of autotaxin-lysophosphatidate signaling-related proteins.
Figure 5
Figure 5
The impact of tumoral LPA3 on prognosis in overall metastatic breast cancer (A), lung metastasis (B), and stromal LPA3 in brain metastasis (C).
See this image and copyright information in PMC

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