Elevated neutrophil-to-lymphocyte ratio is associated with nutritional impairment, immune suppression, resistance to S-1 plus cisplatin, and poor prognosis in patients with stage IV gastric cancer

Abstract

Gastric cancer continues to be a major cause of morbidity and mortality worldwide. Recently, there has been a growing interest in the host inflammatory response and there is increasing evidence that the neutrophil to lymphocyte ratio (NLR), which is a useful marker of systemic inflammation, can be an effective prognostic indicator in various types of malignant diseases. A total of 110 patients with stage IV gastric cancer who received chemotherapy of S-1 plus cisplatin were enrolled in this study. Eleven patients did not complete four cycles of the chemotherapy. The patients were divided into two groups with 3.0 of NLR. The percentage of patients with a partial response to chemotherapy was significantly higher in the group of patients with a lower NLR (<3) (19.1 vs. 38.5%, high vs. low NLR group, respectively; P<0.05). The percentage of patients with progressive disease was higher in the high vs. low NLR group (57.4 vs. 25.0%, respectively; P<0.05). NLR levels were significantly inversely correlated with serum levels of prealbumin (P<0.01) and retinol binding protein (P<0.05). NLR levels were also significantly correlated with c-reactive protein levels (P<0.05), white blood cell count (P<0.05) and inversely with the stimulation index (a marker of cell-mediated immune function; P<0.05). Overall survival was significantly longer in patients with a lower NLR (≤ 3.0) than in those with a higher NLR (>3.0). The present study demonstrated that the NLR is a useful marker for resistance to chemotherapy, malnutrition, systemic inflammation and immune suppression. Moreover, the NLR was demonstrated to be a strong prognostic indicator in these patients.

Keywords: Gastric cancer; TS1+cisplatin; immune suppression; inflammation; malnutrition; neutrophil-to-lymphocyte ratio; overall survival rate.

Figure 1.

Nutrition and NLR. In preoperative gastric cancer patients, NLR were significantly negatively correlated with (A) prealbumin and (B) retinol binding protein. NLR, neutrophil/lymphocyte ration.

Figure 2.

Inflammation and NLR. In preoperative gastric cancer patients, NLR were significantly positively correlated with (A) WBC and (B) CRP. NLR, neutrophil/lymphocyte ration; CRP, C-reactive protein.

Figure 3.

SI and NLR. In preoperative gastric cancer patients, NLR were significantly negatively correlated with SI. NLR, neutrophil/lymphocyte ration; SI, stimulation index.

Figure 4.

NLR of patients with stage IV gastric cancer and overall survival. Kaplan-Meier analysis for overall survival according to NLR. The patients were stratified into two groups: NLR<3.0% and NLR>3.0%. Survival analysis was performed in 110 stage IV patients with follow-up.