Prognostic relevance of lactate dehydrogenase in advanced pancreatic ductal adenocarcinoma patients

Yuanyuan Xiao,Zhihui Xie,Naiqing Zhao,Wen Chen,Guoyou Qin,Hua Xie,Zhenyi Shao

doi:10.1186/s12885-016-3012-8

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.

Highlights

The prognostic role of pretreatment serum lactate dehydronegase (LDH) has been well established in many malignant tumors, albeit it remains under-discussed in pancreatic cancer
We sketched KaplanMeier survival curves with regard to baseline LDH levels: for both groups of patients, an elevated baseline LDH level was associated with significantly compromised overall survival (OS) (Fig. 1)
For advanced pancreatic ductal adenocarcinoma (PDAC) patients who underwent subsequent palliative chemotherapy, univariate Cox model found that pretreatment LDH level was significantly associated with deteriorated survival, and this notable association was maintained in the multivariate model: compared with patients having a normally ranged LDH level, an elevated LDH level was associated with an hazards ratio (HR) of 2.47

Summary

Introduction

The prognostic role of pretreatment serum lactate dehydronegase (LDH) has been well established in many malignant tumors, albeit it remains under-discussed in pancreatic cancer. As a solid tumor which featured in hypoxia, some newly uncovered evidence has suggested that the “Warburg effect” may play a central role in the initiation, progression, and invasion of pancreatic cancer [2]. The over-expression of LDHA inevitably promotes the production of LDH by cancer cells. The prognostic value of serum LDH levels in cancer has long been a topic of considerable research interest. The hazardous role of an elevated pretreatment LDH levels in survival of patients with small-cell lung cancer, nasopharyngeal cancer, colon cancer, and aggressive lymphoid

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