Background: The goal of this study was to investigate the expression of sarcosine metabolism-related proteins, namely glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX), in the different breast cancer subtypes and to assess the implications of differences in expression pattern according to subtype. Methods: We analyzed the expression of GNMT, SARDH, and PIPOX in a tissue microarray of 721 breast cancer cases using immunohistochemistry (IHC). We classified breast cancer cases into subtype luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) according to the status for the estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67. Sarcosine metabolism phenotype was stratified according to IHC results for GNMT, SARDH, and PIPOX: GNMT(+), SARDH and PIPOX(-) was classified as high sarcosine type; GNMT(-), SARDH or PIPOX(-) as low sarcosine type; GNMT(+), SARDH or PIPOX(+) as intermediate sarcosine type, and GNMT(-), SARDH and PIPOX(-) as null type. Results: Expression of sarcosine metabolism-related proteins differed significantly according to breast cancer subtype (GNMT, p = 0.005; SARDH, p = 0.012; tumoral PIPOX, p = 0.008; stromal PIPOX, p < 0.001). These proteins were the most frequently expressed in HER-2 type tumors and the least in TNBC. Sarcosine metabolism phenotype also varied according to breast cancer subtype, with high sarcosine type the most common in HER-2, and null type the most common in TNBC (p = 0.003). Univariate analysis revealed that GNMT expression (p = 0.042), tumoral PIPOX negativity (p = 0.039), and high sarcosine type (p = 0.021) were associated with shorter disease-free survival (DFS). Multivariate analysis also revealed GNMT expression was an independent factor for shorter DFS (hazard ratio: 2.408, 95% CI: 1.154-5.024, p = 0.019).Conclusion: Expressions of sarcosine metabolism-related proteins varied according to subtype of breast cancer, with HER-2 type tumors showing elevated expression of these proteins, and TNBC subtype showing decreased expression of these proteins. Expression of sarcosine metabolism-related proteins was also associated with breast cancer prognosis.
|Journal||Journal of translational medicine|
|Publication status||Published - 2014 May 28|
Bibliographical noteFunding Information:
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A1002886). This study was supported by a grant from National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1420080).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)