- 2026-07
- Clinical and translational radiation oncology 59
Study Design
- Type
- Observational
- Sample size
- n = 288
- Population
- 288 patients with stage I-III rectal cancer
- Methods
- Prospective cohort study; blood collected around diagnosis; plasma serine and glycine measured by GC-MS/MS; regression models for relative risks and hazard ratios
- Duration
- 5 years
- Funding
- Unclear
Introduction
There is substantial variation in radiotherapy response among patients with rectal cancer. The amino acids serine and glycine have been proposed as radiosensitizers in preclinical studies. Here, we explored associations between plasma serine, glycine, and their ratio and clinical outcomes following neoadjuvant treatment for rectal cancer, including tumour downstaging and cancer recurrence.Methods
Based on a prospective cohort study, 288 patients with stage I-III rectal cancer were included. Blood was collected around diagnosis and plasma levels of serine and glycine were measured using GC-MS/MS. Tumour downstaging was defined as T-classification downstaging (pT < cT) after neoadjuvant treatment and recurrence included locoregional recurrences and distant metastases occurring in the 5-years after surgery. Regression models were used to calculate relative risks (RR) and hazard ratios (HR) and their 95% confidence intervals (CI) for tumour downstaging and recurrence, respectively.Results
Tumour downstaging was observed in 41% (n = 117) of the patients and the 5-year recurrence rate was 23% (n = 67). Serine, glycine, and their ratio were not associated with tumour downstaging. A higher serine/glycine ratio was associated with a lower risk of cancer recurrence (HRperdoubling 0.47, 95%CI 0.22-0.99) and tumour downstaging was associated with lower risk of cancer recurrence (HR 0.40, 95%CI 0.22-0.70).Conclusion
This is the first study demonstrating a potential association between the serine/glycine ratio, an indicator of SHMT enzyme activity, and rectal cancer recurrence. Further studies are warranted to confirm these findings, as well as investigate underlying biological mechanisms and potentially explore strategies to target SHMT enzyme activity in the context of cancer treatment.
Research Insights
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