Serine hydroxymethyltransferase 2 predicts unfavorable outcomes in multiple cancer: a systematic review and meta-analysis

Juan Du; Yongkang Huang; Suxian Jing; Yongjian Pei; Yajuan Qian; Yuanyuan Zeng

doi:10.21037/tcr-21-2485

Serine hydroxymethyltransferase 2 predicts unfavorable outcomes in multiple cancer: a systematic review and meta-analysis

Transl Cancer Res. 2022 Mar;11(3):444-455. doi: 10.21037/tcr-21-2485.

Authors

Juan Du^#¹, Yongkang Huang^#², Suxian Jing^#¹, Yongjian Pei², Yajuan Qian², Yuanyuan Zeng^{1

3

4}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Soochow University, Suzhou, China.
³ Suzhou Key Laboratory for Respiratory Diseases, Suzhou, China.
⁴ Institute of Respiratory Diseases, Soochow University, Suzhou, China.

^# Contributed equally.

Abstract

Background: Serine hydroxymethyltransferase (SHMT) is critical for one-carbon unit metabolism and is increasingly reported to be associated with tumor patients' outcomes. Thus, we designed and performed this meta-analysis to reveal its prognostic role and relationship with clinicopathological characteristics in human cancer.

Methods: A systematic search of PubMed, Embase, Web of Science and Cochrane Library (CENTRAL) was carried out. Two reviewers independently screened all references for eligibility according to the inclusion criteria. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality and data was extracted for the meta-analysis.

Results: Ten studies, composed of 1,942 patients in total, were included in this meta-analysis. Higher expression of SHMT2 means an unfavorable prognosis [overall survival: hazard ratio (HR) =2.14, 95% confidence interval (CI): 1.53 to 2.99; progression-free survival (PFS)/disease-free survival (DFS)/recurrence-free survival (RFS): HR =1.90, 95% CI: 1.31 to 2.76]. Furthermore, higher SHMT2 expression is associated with larger tumor size [odds ratio (OR) =2.09, 95% CI: 1.58 to 2.77], more lymph node invasions [OR =2.67, 95% CI: 1.78 to 4.00), and higher tumor node metastasis classification (TNM) stage (OR =2.23, 95% CI: 1.55 to 3.21). Higher expression of SHMT2 is also related to higher histopathological grade (OR =3.46, 95% CI: 1.46 to 8.27) and distant metastasis (OR =1.25, 95% CI: 0.32 to 4.90), however, with significant heterogeneity (I²=61%, P=0.08 for distant metastasis; I²=82%, P<0.001 for histopathological grade). The prognostic clinical role of SHMT1 in clinical patients has not been directly investigated yet.

Discussion: SHMT2 may serve as a promising prognostic biomarker in various cancer, especially in the alimentary system. Further large-scale studies are warranted to verify the possible effect.

Keywords: Serine hydroxymethyltransferase (SHMT); clinicopathological features; human cancers; predictive biomarker.