Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer.

Abstract

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.

• Authors: Ja Kyung Yoon, Do Hee Kim, Ja Seung Koo
• Journal: Journal of translational medicine (J Transl Med) Vol. 12 Pg. 149 (May 28 2014) ISSN: 1479-5876 [Electronic] England
• PMID: 24884785 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ki-67 Antigen
• Receptors, Estrogen
• Receptors, Progesterone
• Sarcosine Oxidase
• Sarcosine Dehydrogenase
• Glycine N-Methyltransferase
• ERBB2 protein, human
• Receptor, ErbB-2
• Sarcosine

Topics

• Breast Neoplasms (genetics, metabolism, pathology)
• Female
• Glycine N-Methyltransferase (metabolism)
• Humans
• In Situ Hybridization, Fluorescence
• Ki-67 Antigen (metabolism)
• Middle Aged
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Progesterone (metabolism)
• Sarcosine (metabolism)
• Sarcosine Dehydrogenase (metabolism)
• Sarcosine Oxidase (metabolism)