Mitochondrial
serine hydroxylmethyltransferase 2 (SHMT2) is a key
enzyme in the
serine/
glycine synthesis pathway. SHMT2 has been implicated as a critical component for
tumor cell survival. The aim of the present study was to evaluate the prognostic value and efficiency of SHMT2 as a
biomarker in patients with
breast cancer. Individual and pooled survival analyses were performed on five independent
breast cancer microarray datasets. Gene signatures enriched by SHMT2 were also analyzed in these datasets. SHMT2
protein expression was detected using immunohistochemistry (IHC) assay in 128 breast
cancer cases. Gene set enrichment analysis revealed that SHMT2 was significantly associated with gene signatures of mitochondrial module,
cancer invasion,
metastasis and poor survival among
breast cancer patients (p<0.05). The clinical relevance of SHMT2 was validated on IHC data. The mitochondrial localization of SHMT2
protein was visualized on IHC staining. Independent and pooled analysis confirmed that SHMT2 expression was associated with
breast cancer tumor aggressiveness (TNM staging and Elson grade) in a dose-dependent manner (p<0.05). The prognostic performance of SHMT2
mRNA was comparable to other gene signatures and proved superior to TNM staging. Further analysis results indicated that SHMT2 had better prognostic value for
estrogen receptor (ER)-negative
breast cancer patients, compared to ER-positive patients. In cases involving stage IIb
breast cancer,
chemotherapy significantly extended survival time among patients with high SHMT2 expression. These results indicate that SHMT2 may be a valuable prognostic
biomarker in ER-negative
breast cancer cases. Furthermore, SHMT2 may be a potential target for
breast cancer treatment and
drug discovery.