Prognostic relevance of lactate dehydrogenase in advanced pancreatic ductal adenocarcinoma patients

Abstract

BackgroundThe prognostic role of pretreatment serum lactate dehydronegase (LDH) has been well established in many malignant tumors, albeit it remains under-discussed in pancreatic cancer. In the present study, we aimed to assess the association between baseline LDH levels and overall survival (OS) in advanced pancreatic ductal adenocarcinoma (PDAC) patients who did and did not receive subsequent chemotherapy.MethodsIn total, 135 retrospectively determined patients with locally advanced or metastatic PDAC, who were diagnosed between 2012 and 2013, were analyzed. Baseline LDH levels were detected within 20 days after histopathological confirmation of the diagnosis. Multivariate Cox proportional hazards regression model was applied to estimate the adjusted hazards ratio (HR) for LDH levels and OS of PDAC. We used restricted cubic spline (RCS) to further investigate dose-effect relationship in the association.ResultsHaving adjusted for possible confounders, we found that in advanced PDAC patients who went through subsequent chemotherapy, an elevated pretreatment LDH level (≥250 U/L) had an adjusted HR of 2.47 (95% CI = 1.28–4.77) for death, but patients, who did not receive chemotherapy, had no significant HR (adjusted HR = 1.57; 95% CI = 0.83–2.96). RCS fitting results revealed a steep increase in HR for PDAC patients received chemotherapy with a baseline LDH > 500 U/L.ConclusionsPretreatment LDH levels had noticeable prognostic value in PDAC patients who received subsequent chemotherapy. Tackling elevated LDH levels before the initiation of chemotherapy might be a promising measure for improving OS of patients after treatment for their advanced PDAC. Studies with a large sample size and a prospective design are warranted to substantiate our findings.

Prognostic value of pretreatment serum lactate dehydrogenase level in pancreatic cancer patients

“…On the other hand, there is evidence favoring that the inverse association between high pretreatment serum LDH level and poor OS may reflect heavy tumor burden or tumor aggressiveness. [5,6] Therefore, dynamically monitoring changes of post-therapy serum LDH level may also help to predict the therapeutic response and prognosis in patients with pancreatic cancer. For instance, a study by Xiao et al [46] found that postoperative high serum LDH was significantly correlated with worse OS in patients with early-stage PC.…”

“…Lactate dehydrogenase (LDH)—a common serum enzyme—participates in the conversion of pyruvate into lactate, and plays a critical role in maintaining the continued glycolysis, which is closely associated with tumor initiation and progression. [5–7] It has been considered that LDH may act as an indicator for tumor burden and aggressiveness because it is required for tumor maintenance. [5,6] Moreover, there is evidence supporting that serum LDH levels increased in many cancers and was associated with prognosis of various cancer patients, including PC.…”

“…[5–7] It has been considered that LDH may act as an indicator for tumor burden and aggressiveness because it is required for tumor maintenance. [5,6] Moreover, there is evidence supporting that serum LDH levels increased in many cancers and was associated with prognosis of various cancer patients, including PC. [8–18]…”

The Neutrophil/Lymphocyte Ratio at Diagnosis Is Significantly Associated with Survival in Metastatic Pancreatic Cancer Patients

“…LDH is the enzyme converting pyruvate to lactate in anaerobic conditions, and as PDAC is a poorly vascularized cancer type, hypoxia plays an important role in its progression. Serum LDH levels have been reported to be associated with PDAC prognosis and response to treatment [ 22 , 23 , 24 ], and the relation between NLR and LDH is another interesting area for future research.…”

Targeting Pyruvate Kinase M2 and Lactate Dehydrogenase A Is an Effective Combination Strategy for the Treatment of Pancreatic Cancer

“…LDHA is predominantly expressed in muscle tissue and at low levels in other tissues. High LDHA expression has been reported in a number of malignancies, including pancreatic cancer, and has been associated with tumor development, invasion, and metastasis [21,22,23]. Targeting of LDHA with siRNA or small molecule inhibitors has been reported to increase oxygen consumption and reactive oxygen species production, reduce glucose uptake and lactate production, and decrease tumor cell growth [21,24,25,26].…”