Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 May 28:12:149.
doi: 10.1186/1479-5876-12-149.

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

Ja Kyung Yoon, Do Hee Kim, Ja Seung Koo  1
Affiliations

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

Ja Kyung Yoon et al. J Transl Med. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer.
Figure 2
Figure 2
A heatmap of the expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer. T, tumor, S, stroma, red: positive, green: negative.
Figure 3
Figure 3
Disease-free survival and overall survival according to the expression of sarcosine metabolism-related proteins and sarcosine metabolism phenotype.
Figure 4
Figure 4
Overall survival according to the expression of SARDH in luminal A type breast cancer.
Figure 5
Figure 5
Disease-free survival and overall survival according to the expression of GNMT and sarcosine metabolism phenotype in luminal B type breast cancer.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009;457:910–914. doi: 10.1038/nature07762. - DOI - PMC - PubMed
    1. Khan AP, Rajendiran TM, Ateeq B, Asangani IA, Athanikar JN, Yocum AK, Mehra R, Siddiqui J, Palapattu G, Wei JT, Michailidis G, Sreekumar A, Chinnaiyan AM. The role of sarcosine metabolism in prostate cancer progression. Neoplasia. 2013;15:491–501. - PMC - PubMed
    1. Baum CE, Price DK, Figg WD. Sarcosine as a potential prostate cancer biomarker and therapeutic target. Cancer Biol Ther. 2010;9:341–342. doi: 10.4161/cbt.9.5.11310. - DOI - PMC - PubMed
    1. Cernei N, Heger Z, Gumulec J, Zitka O, Masarik M, Babula P, Eckschlager T, Stiborova M, Kizek R, Adam V. Sarcosine as a potential prostate cancer biomarker–a review. Int J Mol Sci. 2013;14:13893–13908. doi: 10.3390/ijms140713893. - DOI - PMC - PubMed
    1. Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumours. Nature. 2000;406:747–752. doi: 10.1038/35021093. - DOI - PubMed

Publication types

MeSH terms