Elsevier

Clinica Chimica Acta

Volume 479, April 2018, Pages 181-189
Clinica Chimica Acta

Review
Prognostic role of the neutrophil-to-lymphocyte ratio in pancreatic cancer: A meta-analysis containing 8252 patients

https://doi.org/10.1016/j.cca.2018.01.024Get rights and content

Highlights

  • Low NLR was obviously associated with longer OS and DFS compared to high NLR in pancreatic cancer.

  • The association between NLR and clinical parameters was explored.

  • The relatively large sample size strengthened the convincing of the results.

  • NLR might be a promising prognostic biomarker for pancreatic cancer.

Abstract

Several studies were carried out to explore the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in pancreatic cancer, however, with contradictory results. The objectives of this study were to summarize the prognostic value of NLR in pancreatic cancer. Embase, PubMed and Cochrane Library were comprehensively retrieved. All the cohort studies focusing on the prognostic value of NLR in pancreatic cancer were eligible. 37 papers containing 43 cohort studies with pancreatic cancer were finally included into this study. The results presented that patients with low NLR might have longer OS when compared to the patients with high NLR (HR = 1.81, 95%CI = 1.59–2.05, P < 0.00001; I2 = 82%). Similar results were detected in the subgroup analyses of OS, which was based on the analysis model, ethnicity, treatment, sample size and cut-off value. In additions, low NLR was significantly associated with longer DFS when compared to high NLR in pancreatic cancer (HR = 1.66, 95%CI = 1.17–2.35, P = 0.005; I2 = 67%). Moreover, patients with low NLR had significantly smaller tumor size (P = 0.0007), better differentiation (P = 0.003), earlier stage (P = 0.02) and low CA-199 level (P = 0.007). In conclusion, it was revealed that low NLR was a favorable predictor of OS and DFS in patients with pancreatic cancer, and NLR is a promising prognostic biomarker for pancreatic cancer.

Introduction

Pancreatic cancer is one of the most common digestive system neoplasms, which is the fourth leading cause of cancer deaths in the United States, and causes estimated 227,000 deaths a year around the world [1,2]. Risk factors of pancreatic cancer include age, tobacco smoking, and nutrition conditions. Some benign diseases such as chronic pancreatitis and diabetes mellitus, as well as some germline diseases including hereditary pancreatitis and Familial atypical mole–multiple melanoma (FAMMM) are also closely related to pancreatic cancer [3,4]. Although great developments have been made in the early diagnosis and treatment of pancreatic cancer, the prognostic outcomes of patients with pancreatic cancer remains disappointing. And it is reported that the 5-year overall survival (OS) is lower than 7% for patients with pancreatic cancer, even those receiving curative surgery have an OS no >25% [4].

In view of the disappointing prognosis of patients with pancreatic cancer, more and more researchers turn their attentions to the biomarkers to predict the prognosis and optimize the treatment. And the interesting biomarkers includes carbohydrate antigen 19-9 (CA19-9), Eastern Cooperative Oncology Group system (ECOG), C-reactive protein (CRP) and so on [5,6]. However, there's still in lack of prognostic biomarkers with enough sensitivity and specificity.

Chronic pancreatitis, characterized by the persistent inflammation of the pancreas, is one of the leading risk factors of pancreatic cancer [7]. Pancreatic cancer itself, would in turn trigger inflammatory response by both actively secreting and passively releasing pro-inflammatory cytokines [8,9]. In additions, chemotherapies and radiotherapies could also affect the tumor microenvironment (TME), thus promoting the inflammatory response in pancreatic cancer [10]. And systemic inflammatory response (SIR) has been proved to be associated with prognosis of various tumors [11]. Recently, several studies have investigated the possibilities of using neutrophil-to-lymphocyte ratio (NLR), another inflammation biomarker, as a prognostic biomarker of pancreatic cancer [[12], [13], [14], [15]]. NLR is the ratio of two immune cells and can be easily obtained by blood cell count. Previous studies presented that level of NLR might be significantly associated with the prognosis in several tumors, including colorectal cancer [13], lung cancer [16], urologic cancer [17], gastric cancer [18], esophageal cancer [19] and so on.

Currently, only two meta-analyses focused on the prognostic significance of NLR for pancreatic cancer, which only included 9 cohorts and 11 cohorts, respectively [20,21]. The limited included studies of these two meta-analyses heavily decreased the convening and applicability of the conclusion [20,21]. Besides, in Cheng et al. study, no subgroup analysis has been done to deal with the existing heterogeneity. Simply pooling the results of different studies with different baseline, demographic features and different cut-off values of NLR have rendered their study more susceptible to various risk of biases [20]. Meanwhile, more new studies focusing on the association between NLR and prognosis in pancreatic cancer have been conducted, still with controversial results [[22], [23], [24], [25]]. Therefore, the current meta-analysis containing more studies was conducted to comprehensively explore the association between NLR and prognosis in pancreatic cancer.

Section snippets

Materials and methods

This study was performed in compliance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) for reporting systemic review and meta-analysis [26].

Literature search

As shown in Fig. 1, a total of 309 papers were initially identified and 67 papers were excluded for the duplicative information. Regarding the remaining 242 papers, 195 papers were directly excluded by scanning the titles or abstracts. For the 47 potentially relevant studies, the full-texts of them were carefully read. Among these 47 studies, 8 studies were excluded because not focusing on the topic and 2 studies were excluded for the duplicated patients. At last, 37 studies containing 43

Discussion

Currently, pancreatic cancer is one of the leading causes of cancer death in the world [66]. There are several reasons for its high mortality. (i) PDAC is a highly invasive carcinoma which usually metastases at early stage. This has made it impossible for many patients to get curative surgical treatment; (ii) Pancreatic cancer is relatively insensitive to current chemotherapy, radiotherapy and targeted therapy; (iii) Pancreatic cancer cells harbor multiple genetic and epigenetic alterations,

Author contributions statement

Study concepts and design: Zhiyuan Hua, Yongping Zhou; Literature search: Yongping Zhou and Junsheng Fan; Data extraction: Yongping Zhou, Sijin Cheng and Wenzhou Ding; Manuscript preparation and revision: Junsheng Fan, Zhiyuan Hua and Qian Wei. All authors reviewed the manuscript.

Conflicts of interest

The authors have declared no conflicts of interest.

Financial support

None.

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    These authors contributed equally to this work.

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