AIM: To investigate the significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) in the prognosis of patients with gastric cancer (GC).

METHODS: The clinical data of 291 GC patients were analysed retrospectively; these patients were divided into two groups according to their preoperative NLR: a high-NLR group (NLR ≥ 3.5, 131 cases) and a low-NLR group (NLR < 3.5, 160 cases). The clinicopathological characteristics and five-year survival rates of the two groups were compared. The NLR and other clinicopathological factors were subjected to univariate and multivariate survival analysis to evaluate the effects of the NLR on the prognosis of GC patients.

RESULTS: The lowest preoperative NLR among the 291 patients was 0.56, whereas the highest preoperative NLR was 74.5. The mean preoperative NLR was 5.99 ± 8.98. Age, tumour size, T staging, tumour-node-metastasis (TNM) staging and platelet count were significantly different between the high- and low-NLR groups (P < 0.05). The five-year survival rate of the high-NLR group was 17.0%, which was significantly lower than that of the low-NLR group (43.6%; 17.0% vs 43.6%, P < 0.05). The univariate analysis results showed that the five-year survival rate was related to age, tumour size, T staging, N staging, TNM staging, carcinoembryonic antigen value and NLR (P < 0.05). Multivariate analysis results showed that the NLR was an independent risk factor that likely affected the five-year survival rate of GC patients (P = 0.003, HR = 0.626, 95%CI: 0.460-0.852).

CONCLUSION: The preoperative NLR could be used as a prognostic factor for GC patients; in particular, a high NLR corresponded to poor prognosis of GC patients.

Gastric cancer (GC) is one of the most common types of gastrointestinal cancer; the mortality of GC ranks second among all malignancies[1]. Although the incidence of GC declined in recent years, prognosis has not greatly improved, and the five-year accumulative survival rate remains at approximately 25%[2]. GC is mainly treated by radical surgery; thus, factors associated with the prognosis of GC should be determined to effectively assist intervention therapy and to improve patient outcomes. The body’s inflammatory response plays an important role in tumour occurrence and development[3]. Inflammatory responses can inhibit apoptosis, promote angiogenesis and damage DNA, thereby promoting tumour growth and proliferation[4,5]. In cancer patients who are in the aggressive phase, inflammatory response indicators, such as C-reactive protein levels and platelet count, are usually higher and are related to poor prognosis[6,7]. Similarly, the body’s inflammatory response can cause changes in the peripheral white blood cell count, which is reflected as an increased neutrophil count and reduced lymphocyte count[8]. Therefore, NLR could be used as a good indicator of the systemic inflammatory state of cancer patients. NLR is closely related to the prognosis of various malignant tumours, such as liver cancer, colorectal cancer, breast cancer, bladder cancer and non-small cell lung cancer[9-14]. However, few studies have investigated the relationships of NLR and prognosis of GC patients[15-17]. This study aimed to investigate the effects of preoperative NLR in the prognosis of GC patients; our study also provided a reference for diagnostic and treatment strategies for GC.

Abnormal phenotypes of malignant cancer cells likely stimulate the accumulation of inflammatory cells and destroy the tumour-surrounding tissues, thereby causing a series of non-specific inflammatory responses. As a tumour grows, these inflammatory responses likely increase the peripheral blood neutrophil count and decrease the lymphocyte count; as a result, NLR increases. This result is consistent with those of previous studies[15,16,19]. Our study further found that the proportion of patients in the high-NLR group increased as the tumour invasion depth increased and the disease progressed; this finding is also consistent with those in previous studies. Shimada et al[15] performed a logistical regression analysis of clinicopathological factors that likely influence the increase in NLR and found that old age and high blood platelet count are independent risk factors of high NLR; the data of the present study showed that age and tumour size were independent risk factors that likely affected the increase in NLR.

High NLR is related to poor prognosis of patients with various malignant tumours[9,10,12,14]. Hirashima et al[17] revealed that NLR is related to the prognosis of patients with GC in the early stage; however, they did not further analyse whether NLR is an independent factor affecting the prognosis of GC patients. Jung et al[16] investigated patients with stage III and IV GC and found that the overall survival rate of the high-NLR group (≥ 2.0) was significantly lower than that of the low-NLR group. Indeed, NLR is an independent factor affecting patient’s overall survival rate. Shimada et al[15] studied 1028 GC cases subjected to radical surgery and found that the five-year survival rate of patients with high NLR (≥ 4.0) was significantly lower than that of patients with low NLR. Similarly, Shimada et al[15] found that NLR is an independent factor affecting patient’s five-year survival rate. Other scholars[20,21] also investigated patients with advanced GC treated with chemotherapy and found that high NLR is an independent risk factor influencing patient’s disease-free survival period and overall survival rate. In our study, the effect on five-year survival rate of the patients with NLR ≥ 3.5 was apparent compared with that of patients with NLR < 3.5 possibly because NLR was related to the development of GC. Multivariate analysis results showed that NLR was an independent factor that likely affected the patient’s five-year survival rate. Therefore, high preoperative NLR is an indicator of the poor prognosis of patients with GC.

Several explanations have been provided regarding the relationship of high NLR and poor prognosis. For instance, high NLR corresponds to an enhanced response of neutrophils to tumour inflammation; neutrophils secrete angiogenic factors, such as vascular endothelial growth factor, thereby stimulating angiogenesis and promoting tumour growth and metastasis[22]. Alternatively, peripheral blood lymphocytes are decreased, leading to reduced lymphocyte-mediated anti-tumour immune responses, which would accelerate disease progression. Furthermore, systemic inflammation is closely related to nutritional status and decreased organ function in cancer patients; thus, poor prognosis is observed[23].

High preoperative NLR indicated poor cancer prognosis; this result is very significant for cancer prevention and treatment. Moreover, the effects of anti-inflammatory drugs on tumour occurrence and development have been investigated extensively. For example, the prophylactic application of non-steroidal anti-inflammatory drugs (NSAIDs) can reduce the incidence of colon cancer by 40% to 50%; NSAIDs elicit the same preventive effects on lung cancer, oesophageal cancer and stomach cancer[24,25]. In addition, vaccination has been administered to promote an immune response of lymphocytes against tumours, thereby improving patient prognosis[26]. Indeed, patients with high preoperative NLR should be considered as high-risk patients who should be integrated with multi-mode anti-tumour therapies, such as chemotherapy, radiotherapy and immune therapy.

In summary, preoperative NLR was closely related to the prognosis of GC; in particular, a high NLR was an indicator that could be used to determine the poor prognosis of patients with GC. NLR could be determined using a simple, rapid and cost-effective detection technique; this technique could be applied efficiently to predict the prognosis of GC patients and to provide a reference for the integrated treatment of GC for broad applications.