Abstract 739P
Background
Serine hydroxymethyltransferase 2 (SHMT2) has a critical role in serine-glycine metabolism to drive cancer cell proliferation. Expression, function, and underlying mechanisms of SHMT2 in cancer is investigated in this study.
Methods
Pan cancer genomic data was obtained from TCGA project. Statistical analyses were performed for expression and distribution of SHMT2, other target genes and oncogenic signaling pathways in each tumor. Clinical survival outcomes were analyzed by cox proportional hazards model.
Results
SHMT2 mRNA expression and distribution in 10,167 patients across 33 cancers from the TCGA data was analyzed. In univariate analysis SHMT2 expression was associated with a poor overall survival (OS) (HR=1.70, p<0.01), progression free survival (PFS) (HR=1.68, p<0.01), disease free survival (DFS) (HR=1.92, p<0.01) and disease specific survival (DSS) (HR=1.96, p<0.01). Multivariate analysis after adjusting for age, gender, race, stage and histological grade OS (HR=1.34, p<0.01), PFS (HR=1.36, p<0.01), DFS (HR=1.48, p<0.01) and DSS (HR=1.49, p<0.01) was observed. Higher expression of SHMT2 is related to advanced stage (OR =1.47, p<0.01) and higher histopathological grade (OR =1.47, p<0.01). Similar results were observed in multiple cancer types. Positive relation was observed with oncogenic signaling pathways of Cell Cycle (OR 2.62; p < 0.01), Hippo (OR 2.11; p < 0.01), MYC (OR 2.25; p < 0.01), NOTCH (OR 2.27; p < 0.01), NRF2 (OR 3.55; p < 0.01), TP53 (OR 2.45; p < 0.01), TGF-Beta (OR 1.63; p < 0.01), WNT (OR 2.09; p < 0.01). Hypoxia (HIF1A, p<0.01) plays critical roles in metastasis and angiogenesis by upregulating the expression of glycolysis-related enzymes, including HK2 (p<0.01), LDHA (p<0.01) and PDK1(p<0.01). Upregulated expression of these enzymes suppresses entry of pyruvate into the TCA cycle, reducing ROS and promote tumor growth. Interestingly UHRF1 (p<0.01) an intermediate filament protein and ANLN (p<0.01) actin-binding protein was also upregulated, which has role in cell growth, migration, cytokinesis, and affect cell proliferation.
Conclusions
SHMT2 expression is associated with poor clinical outcomes, and responsible for metabolic reprogramming in cancer. SHMT2 might be valuable target for cancer therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Narender Kumar.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.