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LDH stimulates survival, migration, and proliferation of tumour cells, and promotes angiogenesis and metastasis in cases of gastric cancer
- Thread starter ginfreely
- Start date
Abstract
Background
The prognostic significance of lactate dehydrogenase (LDH) and its impact on the outcomes of gastric cancer (GC) is still unclear. We assessed the link between the levels of LDH and the overall survival (OS) and disease-free survival (DFS) in GC patients.Methods
A comprehensive search (both electronic and manual) was carried out in PubMed via MEDLINE, Web of Science (WoS), Experta Medical Database (Embase), and CENTRAL (Cochrane Library) databases for citations that evaluated the strength of association between LDH cut-off levels and OS and/or DFS in GC. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and heterogeneity was assessed.Results
Eighteen studies with 5328 patients were included in our review. The overall pooled HR for OS was 1.48 (95% CI: 1.22-1.80) with high heterogeneity (I2 = 86%). Subgroup analyses showed that the link between LDH and OS was more prominent in Caucasian (HR 1.50 95% CI [0.80, 2.81], p=0.21) than in Asian cohorts (HR, 1.51 95% CI [1.21, 1.87], p=0.002). No significant overall association between LDH and OS (HR = 1.12, 95% CI: 0.76-1.65, p = 0.58) was found. Similar subgroup analyses results were reported for the association between LDH and DFS.Conclusion
In patients with GC, elevated LDH levels may correlate with worse OS and DFS, but the association is not significant. LDH is a significant predictor of OS but not of DFS. Further studies with larger sample sizes and more standardized criteria for defining elevated LDH levels are needed to confirm our findings.
Introduction
Gastric cancer (GC) is associated with high morbidity and mortality (1, 2). Despite advancements in medical technology and treatment options, the prognosis for patients with gastric cancer remains challenging. The disease often presents at an advanced stage, limiting curative treatment options and leading to high mortality rates. Therefore, identifying new prognostic biomarkers that can accurately predict disease outcomes and guide treatment decisions, is crucial (3–6).Lactate dehydrogenase (LDH), an enzyme involved in cellular metabolism, was identified as a possible prognostic biomarker for various malignancies, including gastric cancer. However, the prognostic value of LDH in GC still remains controversial (7). While some studies have suggested a significant association between elevated LDH levels and poor prognosis in gastric cancer patients, other investigations have failed to establish a consistent link. These discrepancies in findings may be attributed to several factors, such as variations in patient populations (ethnicity, age, stage of disease), heterogeneity in study designs (retrospective vs. prospective).
Numerous studies suggest that understanding the link between LDH and cancer can shed light on the metabolic reprogramming that occurs in various cancers, providing insights into the biology of tumor growth and progression. The Warburg effect refers to the distinct metabolic behaviour of cancer cells, wherein they exhibit a preference for glycolysis over mitochondrial oxidative phosphorylation, even under aerobic conditions (8, 9). Recent studies that linked oncogenes and metabolic processes suggested that this transition to aerobic glycolysis may promote cancer cell proliferation (8). LDH is a crucial enzyme that converts pyruvic acid to lactic acid and is over-expressed in all types of cancers. Studies show that LDH stimulates survival, migration, and proliferation of tumour cells, and promotes angiogenesis and metastasis in cases of gastric cancer (10). Elevated levels of LDH were linked to poorer prognosis in a number of cancers, including GC (11, 12). However, there is still no consensus on the association of the expression status and function of LDH-A and the prognosis in gastric cancer patients. To the best of our knowledge, there has been no meta-analysis to synthesize the available evidence. The main goal of this study is to evaluate the prognostic significance of LDH in terms of survival and recurrence of GC.
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