The granulocyte/lymphocyte ratio as an independent predictor of tumour growth, metastasis and progression: Its clinical applications

Abstract

Abstract. Several investigators have suggested that the granulocyte/lymphocyte (G/L) ratio is a good indicator for the evaluation of the condition of a tumour-bearing host, although its prognotic significance is unclear. To further investigate the clinical applications of the G/L ratio, we injected 1x10 5 and 1x106 Lewis lung carcinoma cells (3LLc) into the feet of 4-week-old C57BL/6 mice separated into groups A, B, C and D (1x10 5 cells) and E, F, G and H (1x10 6 cells). For the observation of tumour metastasis and G/L ratio, the mice in groups A-D were sacrificed on days 11, 14, 17 and 21 after inoculation with the 3LLc cells, and the mice in groups E-H on days 7, 11, 14 and 17. The results suggest that in mice the number of granulocytes increases with time after 3LLc cell injection (P<0.05). We also retrospectively investigated the correlation between G/L ratio, clinicopathologic features and prognosis in 62 patients with gastric carcinoma. There was a significant correlation between the G/L ratio and tumour weight (r=0.746, P<0.05), as well as a significant difference between the G/L ratio and the extent of metastases (P<0.05). Additionally, the G/L ratio was significantly associated with lymph node metastasis and higher tumour stage, tumour progression (P=0.017) and 5-year survival (P=0.013). In conclusion, the G/L ratio is associated with tumour progression and shorter survival. The close correlation between G/L ratio and tumour stage or lymph node status suggests that it could be used to predict tumour metastasis, prognosis and overall survival in patients with gastric carcinoma before they undergo surgical treatment.

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…This increase continues with the progression of the disease, reaching a state of acute neutrophilia with neutrophils making~90 % of all circulating white blood cells [32]. Similar increase in circulating neutrophil numbers was seen in other mouse models of cancer including Lewis lung carcinoma [163] as well as in spontaneous mouse models such as the MMTV-PyMT and MMTVWnt1 transgenic mice [32], where tumor initiation is driven by a transgene, rather than an engrafted tumor. In a rat model of 13762NF mammary adenocarcinoma cells, the number of circulating neutrophils did not increase in poorly metastatic cells, whereas the number rose 50-fold in rats bearing a highly metastatic clone [164].…”

“…From then on, a large number of clinical studies have been performed to understand the neutrophil-cancer relationship. Clinical data have often related elevated circulating neutrophil counts or elevated neutrophil-to-lymphocyte ratios (NLRs) as a predictive parameter for poor outcome and formation of distant metastasis in patients with epithelial malignancies [367], including lung [368,170], gastric [159,163,369], renal cell carcinoma [370], ovarian [141], hepatic [143,148,371], pancreatic [138], colon cancer [145,372], and colorectal carcinoma [152] (Table 3). However, Caruso et al [200] observed that when analyzing the amount of tumor-infiltrated neutrophils in advanced gastric carcinoma, in female but not male, patients with higher TANs had a favorable prognosis.…”

The neutrophil/lymphocyte ratio is an independent prognostic indicator in patients with bone metastasis

“…Studies on gastrointestinal cancer have supported the hypothesis that the N/L ratio is significantly associated with overall survival (OS) in patients with colorectal cancer (7,8). In a previous study, we found that the peripheral blood N/L ratio is associated with tumor size and is an independent indicator of survival in patients with rectal carcinoma (9). The independent prognostic role of the peripheral blood N/L ratio for malignant bone metastasis at diagnosis remains to be confirmed.…”

Prediction of chemotherapeutic efficacy using the ratio of neutrophils to lymphocytes in patients with unresectable or recurrent gastric cancer

“…In a previous study, a positive linear correlation was observed between tumor weight and the N/L ratio within an animal model (14), and an increased N/L ratio was associated with poor prognosis because elevated levels of granulocytes promote tumor growth by antagonizing tumor-suppressing lymphocytes. Those results indicate that opposing fluctuations in the neutrophil and lymphocyte counts may be associated with tumor progression.…”

“…A number of studies on gastrointestinal cancer have supported this theory. We have previously reported that the N/L ratio was significantly associated with increased tumor stage and overall survival of patients with gastric and rectal cancer (14,15). One theory is that the high N/L ratio reflects the poor status of the immune system against cancer and/or the progression of cancer, but no previous studies have demonstrated that the N/L ratio may serve as an independent indicator of chemotherapy effect for patients with unresectable or recurrent gastric cancer.…”