Serine hydroxymethyltransferase 2 predicts unfavorable outcomes in multiple cancer: a systematic review and meta-analysis
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".