Neutrophil to lymphocyte ratio and risk of neoplastic progression in patients with Barrett’s esophagus

Abstract

Background and aims: Patient’s with Barrett’s esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). Neutrophil to lymphocyte ratio (NLR) was found to be a predictor of poor prognosis in patients with EAC, however its performance in premalignant esophageal lesions is vague. We aim to evaluate the utility of NLR as a predictor of histologic progression in patients with BE. Methods: A prospective cohort of patients with proven BE in a tertiary referral center was retrospectively analyzed. All biopsies were reviewed by an expert GI pathologist. The discriminatory capacity of NLR was evaluated by Area under the Receiver Operating Curve (AUC) analysis and Cox regression analysis. Results: 324 patients were part of the final cohort, 241 (74.4%) were males, with mean age of 62.3 years. Thirteen patients demonstrated histologic progression to neoplasia over a mean follow up of 3.7 years (annual progression risk of 1.0% per year). The AUC of NLR for progression to high grade dysplasia (HGD) or EAC was 0.88 (95% CI 0.83-0.96), and baseline NLR was associated with 3-fold increase of progression to HGD and EAC during follow up (HR 3.2, 95% CI 1.5-5.8, p<0.001). Notably, in a subgroup analysis of patients with non-dysplastic BE (NDBE) at presentation, NLR was also a risk factor of histologic progression (HR 2.4, 95% CI 1.7-3.4, p<0.001). Conclusion: NLR predicts histologic progression in patients with BE. Patients with NDBE and NLR above 2.4 can be considered for specific surveillance programs with shorter intervals between sessions.

AI-assisted Discovery of an Ethnicity-influenced Driver of Cell Transformation in Esophageal and Gastroesophageal Junction Adenocarcinomas

“…This biphasic-wave pattern may explain why long-standing BE carries low risk of EAC 111 , presumably because a 2 nd wave/'hit' of immune storm is required for cell transformation. Induction of IL8 and its receptors, CXCR1/2 49,[112][113][114][115][116] , increased presence of neutrophils in BE tissues 117 and circulation 83,84 have been reported and increased NETosis within EACs in the setting of peripheral leukocytosis has been shown to carry worse prognosis 118 . In showing that the IL8-neutrophil centric tumor microenvironment is prominently induced in Cau, but not in AAs, which mirrors the ~4-5 fold higher risk of EACs in Cau compared to AAs 119 , our findings suggest that this inflammatory microenvironment is likely to be a driver event.…”

“…We next asked how neutrophil counts and signatures impact the risk of transformation in BE and EAC outcome. [83][84][85] , the neutrophil:lymphocyte ratio (NLR) progressively increased during NDBE→DBE→EAC progression (Figure 6B). However, the increase in NLR in DBE and the extent of increase in NLR in EAC were largely driven by progressive increases in the absolute neutrophil counts (ANC; Figure 6C) and not due to reduced absolute lymphocyte counts (ALC; Figure 6D).…”

Construction of the Interaction Network of Hub Genes in the Progression of Barrett’s Esophagus to Esophageal Adenocarcinoma

“… 4 BE is thought to evolve into EACs through a series of genetic and epigenetic alterations that accumulate in metaplastic cells, giving them an advantage in progressive growth, ultimately leading to malignancy. 5 Most EAC patients are unaware of the medical history of BE, or do not have timely intervention for BE, resulting in advanced tumor progression when the patients are diagnosed with EAC. Therefore, finding biomarkers for early diagnosis of EAC and high-risk BE patients has important preventive significance and clinical value.…”

Prediction of progression in Barrett’s esophagus: does inflammation hold the key?

“…However, most have not progressed beyond Phase 1 or Phase 2 studies given the challenge with prospective validation [3]. In this issue of Endoscopy, Peleg et al take a novel approach to this elusive quest, by using the neutrophil to lymphocyte ratio (NLR) in peripheral blood samples to predict progression in a retrospective analysis of a prospectively followed BE cohort [4].…”

“…"Confounding of the association between metaplasia and neoplasia and elevated neutrophil to lymphocyte ratio (NLR) by other variables such as age, sex, obesity (which causes a systemic inflammatory state), and aspirin or statin use (noted to be higher in the high NLR group) also needs to be carefully assessed in subsequent studies." Peleg et al [4] hypothesized that given the known association between esophageal inflammation and neoplasia, an elevated NLR may be associated with an increased BE progression risk.…”