Research Information System
Turkish Journal of Colorectal Disease, vol.35, pp.164-165, 2025 (Scopus, TRDizin)
Aim: Serum lactate dehydrogenase (LDH) may be a prognostic marker in metastatic colorectal cancer (mCRC). However, mCRC is a heterogeneous disease, and data on LDH-related subgroups are limited. This study aimed to investigate clinical and molecular features associated with LDH in mCRC. Method: Demographic, clinical, treatment response, and survival data from a retrospective cohort of patients diagnosed with synchronous mCRC between 2019 and 2023 were analyzed according to serum LDH levels. Lactate dehydrogenase A (LDHA) gene expression and molecular features were assessed in an independent cohort. Results: The clinical cohort included 135 patients. The median LDH level was 231 U/L (range: 106-5,655), and 55.1% (n=75) of patients had high LDH. The presence of liver metastases (p=0.037), the number of liver metastases (≥5 vs. <5, p=0.035), carcinoembryonic antigen (p=0.000), carbohydrate antigen 19–9 (p=0.042), and C-reactive protein (p=0.002) levels were significantly associated with high LDH. Among patients with liver-only metastases, high LDH was significantly associated with worse overall survival (OS) (19.7 months [95% confidence interval (CI): 13.8-28.1] vs. 39.0 months (95% CI: 19.8-59.2), p=0.017). Non-responders to 5-fluorouracil, leucovorin, and oxaliplatin had higher LDH levels (p=0.016) and worse OS [11.4 months (95% CI: 6.2-12.7) vs. not reached, p=0.002]. Among 84 patients in the independent mCRC cohort, 16.7% (n=14) had high LDHA expression in tumor tissue. High LDHA expression was associated with lower microsatellite instability scores (p=0.048) and higher hypoxia scores (p for Buffa=0.001, Winter=0.003), but not with tumor mutational burden or aneuploidy score. Expression of metabolic–epithelial–mesenchymal transition pathway genes was correlated with LDHA expression. Conclusion: LDH may be a potential marker in microsatellite-stable (MSS), nonimmunogenic, liver-dominant mCRC. Whether LDH could serve as a biomarker for immunotherapy studies in MSS colorectal cancer warrants investigation in future studies.