ReviewPrognostic role of the neutrophil-to-lymphocyte ratio in pancreatic cancer: A meta-analysis containing 8252 patients
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.
References (78)
- et al.
Pancreatic cancer
Lancet
(2016) - et al.
The prognostic role of neutrophils to lymphocytes ratio and platelet count in gastric cancer: a meta-analysis
Int. J. Surg.
(2015) - et al.
Prognostic impact of preoperative NLR and CA19-9 in pancreatic cancer
Pancreatology
(2016) - et al.
Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio
Am. J. Surg.
(2010) - et al.
The combination of systemic inflammation-based marker NLR and circulating regulatory T cells predicts the prognosis of resectable pancreatic cancer patients
Pancreatology
(2016) - et al.
Preoperative platelet-to-lymphocyte ratio improves the performance of the international consensus guidelines in predicting malignant pancreatic cystic neoplasms
Pancreatology
(2016) - et al.
Pretreatment C-reactive protein level predicts outcome and patterns of failure after chemoradiotherapy for locally advanced pancreatic cancer
Pancreatol. Off. J. Int. Assoc. Pancreatol.
(2015) - et al.
Duodenal stenting followed by systemic chemotherapy for patients with pancreatic cancer and gastric outlet obstruction
Pancreatology
(2016) - et al.
Cancer-related inflammation: common themes and therapeutic opportunities
Semin. Cancer Biol.
(2012) - et al.
Tumor-associated transforming growth factor-beta and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients
Am. J. Pathol.
(1999)
Cancer statistics, 2017
CA Cancer J. Clin.
Epidemiology of pancreatic cancer: an overview
Nat. Rev. Gastroenterol. Hepatol.
Pancreatitis-diabetes-pancreatic cancer: summary of an NIDDK-NCI workshop
Pancreas
Can molecular biomarkers change the paradigm of pancreatic cancer prognosis?
Biomed. Res. Int.
Acute-phase protein response and survival duration of patients with pancreatic cancer
Cancer
The pancreatic cancer microenvironment: a true double agent
J. Surg. Oncol.
Cancer-related inflammation and treatment effectiveness
Lancet Oncol.
Environmental immune disruptors, inflammation and cancer risk
Carcinogenesis
Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer
World J. Gastrointest. Oncol.
Immunity, Inflammation, and Cancer
Cell
Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients
Ann. Surg. Oncol.
Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis
Int. J. Cancer
NLR-regulated pathways in cancer: opportunities and obstacles for therapeutic interventions
Cell. Mol. Life Sci.
Preoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict survival in patients with non-small cell lung cancer
World J. Surg. Oncol.
Prognostic role of neutrophil to lymphocyte ratio in lung cancers: a meta-analysis including 7,054 patients
Onco Targets Ther.
Pretreatment neutrophil to lymphocyte ratio as a prognostic predictor of urologic tumors: a systematic review and meta-analysis
Medicine (Baltimore)
Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and meta-analysis
Ann. Surg. Oncol.
Prognostic role of the neutrophil-to-lymphocyte ratio in pancreatic cancer: a meta-analysis
Sci. Rep.
Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: a meta-analysis
World J. Gastroenterol.
Significance of baseline and change in neutrophil-to-lymphocyte ratio in predicting prognosis: a retrospective analysis in advanced pancreatic ductal adenocarcinoma
Sci. Rep.
Neutrophil-lymphocyte ratio predicts survival in pancreatic neuroendocrine tumors
Oncol. Lett.
Prognostic scoring system for patients who present with a gastric outlet obstruction caused by advanced pancreatic adenocarcinoma
World J. Surg.
Predictive value of preoperative peripheral blood neutrophil/lymphocyte ratio for lymph node metastasis in patients of resectable pancreatic neuroendocrine tumors: a nomogram-based study
World J. Surg. Oncol.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
PLoS Med.
Practical methods for incorporating summary time-to-event data into meta-analysis
Trials
The Newcastle–Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis
Appl. Eng. Agric.
Albumin and neutrophil-lymphocyte ratio (NLR) predict survival in patients with pancreatic adenocarcinoma treated with SBRT
Am. J. Clin. Oncol.
Elevated Neutrophil to Lymphocyte Ratio Predicts Survival in Advanced Pancreatic Cancer
Preoperative independent prognostic factors in patients with “Resectable” pancreatic ductal adenocarcinoma following curative resection: neutrophil-lymphocyte ratio and platelet-lymphocyte ratio
Pancreas
Cited by (105)
A case of improved quality of life in a patient with inoperable pancreatic cancer after repeated RFA
2022, Radiology Case ReportsDeconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes
2024, Breast Cancer Research and TreatmentImpact of Recombinant Granulocyte Colony-Stimulating Factor During Neoadjuvant Therapy on Outcomes of Resected Pancreatic Cancer
2024, JNCCN Journal of the National Comprehensive Cancer Network
- 1
These authors contributed equally to this work.