Predictive Value of Neutrophil-To-Lymphocyte Ratio for Distant Metastasis in Gastric Cancer Patients

doi:10.21203/rs.3.rs-1448877/v1

Download PDF

Article

Predictive Value of Neutrophil-To-Lymphocyte Ratio for Distant Metastasis in Gastric Cancer Patients

https://doi.org/10.21203/rs.3.rs-1448877/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Purpose

We aim to investigate the clinical significance of NLR in predicting gastric cancer (GC) metastasis.

Methods

Clinical data from 1,667 consecutive GC patients were retrospectively analyzed. The cut-off was calculated from the receiver operating characteristics (ROC) curve with the maximal Youden index. Prediction probability was obtained by binary logistic regression of GC markers (CEA, CA19-9 and CA72-4) with (P1) or without NLR (P2). Diagnostic efficacy of indicators as well as prediction probability was estimated and compared by ROC analysis. Clinicopathological parameters including inflammatory markers were evaluated for distant metastasis using multiple logistic regression analysis.

Results

The optimal cut-off for NLR was 2.91 with 55% sensitivity and 73.4% specificity. P2 had significantly higher efficacy than P1 for peritoneal metastasis (P = 0.013), osseous metastasis (P = 0.017) and hepatic metastasis (P < 0.001). In multiple logistic regression analysis, age (OR: 0.68, 95% CI: 0.547–0.844), NLR (OR: 2.858, 95% CI: 2.295–3.559), CEA (OR: 2.108, 95% CI: 1.671–2.661), CA19-9 (OR: 1.844, 95% CI: 1.466–2.32), CA72-4 (OR: 2.348, 95% CI: 1.851–2.978) were found to be significantly associated with GC metastasis.

Conclusion

NLR was a risk factor of GC metastasis. Combining CEA, CA19-9, CA72-4 and NLR could better predict metastases in GC.

Gastric cancer

Inflammation

NLR

Distant metastasis

Tumor markers

Gastric cancer (GC) is the second most common cancer in China and the third leading cause of death among all cancer types. About 403,000 new GC cases were reported in 2,015, with a total of 291,000 deaths from it[1]. Due to cancer metastasis and recurrence, the 5-year survival rate of GC patients remains low[2].

Recent studies have borne out claims that inflammation has a vital role in the development and progression of many diseases, including cancers. Inflammation affects every step of tumorigenesis, from initiation, to tumor promotion, to metastatic progression[3]. Subclinical, often undetectable, inflammation may be equally important in increasing cancer risk (for instance, inflammation caused by diabetes)[4]. As one of the most abundant leukocytes, neutrophils play an essential role in cancer progression[5]. Effects of neutrophils in peripheral blood and tumor microenvironment on gastric cancer have been reported[6]. Although tumor-activated neutrophils infiltrating the tumor microenvironment have a significant tumor-promoting effect, they are difficult to obtain. The NLR is a common indicator of systemic inflammation and is defined as absolute neutrophil count divided by absolute lymphocyte count. Cumulative studies have reported that cancer patients have higher NLR levels than healthy people[7]. NLR can act as an independent prognostic factor for many malignant tumors such as lung cancer[8], colorectal cancer[9] and GC[10]. NLR is also closely related to tumor metastasis, especially lymph node metastasis (LNM)[11]. Meanwhile, studies have reported that NLR is not an independent risk factor for LNM in patients with early gastric cancer[12], [13]. NLR is also closely related to distant metastasis of tumor[14]. Although blood cell levels can be routinely obtained, the relationship between blood cell levels and tumor metastasis has not been systematically studied. NLR may be a new non-invasive and convenient biomarker for detecting tumor metastasis. This retrospective study aims to investigate the diagnostic efficacy of NLR for GC metastasis.

2.1. Patient's characteristics

For the entire cohort, the median age was 61 years (range 54–67) and 72.9% were male. 743 (44.6%) patients were diagnosed with metastatic GC. CEA, CA19-9 and CA72-4 in the metastatic group was significantly higher than that in the non-metastatic group (all P < 0.001). Increased absolute neutrophil count and decreased absolute lymphocyte count in the metastasis group resulted in a significant increase in NLR (P < 0.001). At the same time, the albumin level of the metastasis group decreased and the globulin level increased (both P < 0.001) (Table 1). Among all patients, 923 patients were diagnosed with primary tumors, 163 with peritoneal metastasis, 119 with osseous metastasis, 38 with pulmonary metastasis, 46 with lymph node metastasis, 192 with hepatic metastasis, 22 with ovarian metastasis, 122 with multisite metastasis, 8 with brain metastasis and 34 with metastasis of other organs.

Table 1

Demographic and baseline characteristics of patients
Characteristic	Overall (N = 1,667)	Non-metastasis (N = 924)	Metastasis (N = 743)	P value
Gender, no. (%)				< 0.001
Male	1215(72.9)	707(76.5)	508(68.4)
Female	452(27.1)	217(23.5)	235(31.6)
Age, year	61(54–67)	61(54–68)	59(52–67)	0.001
CEA, ng/ml	2.82(1.58–7.07)	2.345(1.37–4.19)	3.88(1.94–17.25)	< 0.001
CA199, U/ml	12.46(6.71–36.87)	10.49(5.95–19.96)	18.22(8.31–124.7)	< 0.001
CA724, U/ml	2.98(1.35–9.43)	2.11(1.17–5.56)	5.32(1.85–21.31)	< 0.001
Erythrocyte,10^12/l	4.2(3.7–4.6)	4.28(3.8–4.67)	4.07(3.6–4.47)	< 0.001
Hemoglobin, g/l	124(104–140)	129(107–143)	119(102–133)	< 0.001
Leukocyte,10^9/l	5.68(4.51–7.11)	5.47(4.4–6.8)	6.04(4.7–7.85)	< 0.001
Neutrophil,10^9/l	3.56(2.67–4.82)	3.29(2.48–4.29)	3.97(2.92–5.75)	< 0.001
Lymphocyte,10^9/l	1.42(1.08–1.83)	1.53(1.18–1.92)	1.29(0.95–1.67)	< 0.001
NLR	2.45(1.67–3.83)	2.1(1.52–3.02)	3.11(2.08–4.86)	< 0.001
Platelet,10^9/l	207(159–263)	205(160-259.75)	209(158–269)	0.317
Monocyte,10^9/l	0.4(0.29–0.52)	0.39(0.28–0.5)	0.4(0.3–0.53)	0.018
Albumin,g/l	38.2(34.8–41.4)	38.6(35.4–41.7)	37.7(34-40.9)	< 0.001
Globulin,g/l	26.2(23.4–29.3)	25.3(22.6–28.2)	27.4(24.7–30.5)	< 0.001
Data are shown as number of cases (percentage) or median (interquartile range); NLR, neutrophil-to-lymphocyte ratio.

2.2. NLR can more efficiently predict gastric cancer metastasis than tumor markers

ROC analysis was performed to evaluate the diagnostic efficacy of NLR in predicting GC metastasis. The optimal cutoffs for CEA, CA19-9, CA72-4 and NLR were determined to be 4.34 (a sensitivity of 48.5% and a specificity of 76.3%), 18.69 (a sensitivity of 49.7% and a specificity of 74.1), 6.96 (a sensitivity of 44.7% and a specificity of 80.7%) and 2.91 (a sensitivity of 55% and a specificity of 73.4%), respectively. The AUC of CEA was 0.647 [95% confidence interval (CI), 0.62–0.674, P < 0.001], of CA19-9 was 0.649 (95% CI, 0.622–0.675, P < 0.001), of CA72-4 was 0.662 (95% CI, 0.636–0.688, P < 0.001) and of NLR was 0.679 (95% CI, 0.653–0.705, P < 0.001) for predicting GC metastasis. The predicting efficacy of NLR was comparable to GC markers (Fig. 1a). The predicted probability of combining GC markers (P1) and the predicted probability of combining GC markers and NLR (P2) was obtained by binary logistic regression. The optimal cutoffs of P1 were 0.39 (a sensitivity of 53.8% and a specificity of 75%) and of P2 was 0.39 (a sensitivity of 64.9% and a specificity of 72.8%). The AUC of P1 was 0.716 (95% CI, 0.691–0.74, P < 0.001) and of P2 was 0.73 (95% CI, 0.705–0.754, P < 0.001). Although the AUC of P1 and P2 was comparable (P = 0.209), the combination of NLR slightly increased diagnostic performance (Table 2).

Table 2

AUC and the cut-point of diagnostic indicators at the maximum of Youden index for GC metastases (N = 1,667)
	AUC	95% CI	Cut-off	Sen	Spe	Youden index	PPV	NPV	P value
NLR	0.679	0.653–0.705	2.91	0.55	0.734	0.284	0.549	0.734	< 0.001
CEA	0.647	0.62–0.674	4.34	0.485	0.763	0.248	0.546	0.719	< 0.001
CA199	0.649	0.622–0.675	18.69	0.497	0.741	0.238	0.537	0.727	< 0.001
CA724	0.662	0.636–0.688	6.96	0.447	0.807	0.254	0.447	0.799	< 0.001
P1	0.716	0.691–0.74	0.39	0.538	0.75	0.333	0.568	0.758	0.209
P2	0.73	0.705–0.754	0.39	0.649	0.728	0.377	0.637	0.733	Ref
AUC, area under receiver operating characteristics; CI, confidence interval; Sen, sensitivity; Spe, specificity; PPV, positive predictive value; NPV, negative predictive value; P, P value for comparison of AUC of reference with other indicators using DeLong’s test; P1, prediction probability obtained by binary logistic regression of CEA, CA199, CA724; P2, prediction probability obtained by binary logistic regression of CEA, CA199, CA724 and NLR; Ref, reference.

We also assessed diagnostic efficacy of NLR for single site metastasis or peritoneal metastasis, ROC analysis was performed using data stratified by different metastasis sites. For peritoneal metastasis (n = 163), AUC (95% CI) of NLR was 0.704 (0.662–0.747), CEA was 0.557 (0.507–0.608), CA19-9 was 0.626 (0.573–0.679) and CA72-4 was 0.694 (0.648–0.739), respectively (Supplementary Table 1). Diagnostic efficacy of prediction probability obtained by binary logistic regression of CEA, CA199, CA724 and NLR was significantly higher than NLR (P = 0.003), CEA (P < 0.001), CA19-9 (P < 0.001) and CA72-4 (P = 0.013) (Fig. 1b). For osseous metastasis (n = 119), AUC (95% CI) of NLR was 0.653 (0.599–0.707), CEA was 0.65 (0.594–0.707), CA19-9 was 0.555 (0.498–0.612) and CA72-4 was 0.586 (0.524–0.648), respectively (Supplementary Table 2). Similar to peritoneal metastasis, diagnostic efficacy of prediction probability was significantly higher than CA19-9 (P < 0.001) and CA72-4 (P = 0.017) but not NLR (P = 0.313) and CEA (P = 0.514) (Fig. 1c). As for hepatic metastasis (n = 192), AUC (95% CI) of NLR was 0.676 (0.633–0.718), CEA was 0.733 (0.693–0.774), CA19-9 was 0.713 (0.669–0.757) and CA72-4 was 0.626 (0.58–0.673) (Supplementary Table 3). Diagnostic efficacy of prediction probability was significantly higher than NLR (P < 0.001), CEA (P = 0.041), CA19-9 (P = 0.002) and CA72-4 (P < 0.001) (Fig. 1d). For multisite metastases, the results of the analysis were similar to the overall cohort (Supplementary Table 4, Fig. 1e). We did not analyze other site such as pulmonary metastasis (n = 38) and ovarian metastasis (n = 22) etc. on account of small sample size (Fig. 1f).

Correlation of NLR and other parameters was showed in the Table 3. In GC patients, NLR showed a positive correlation with CEA, CA19-9, CA72-4 (r = 0.157, 0.173 and 0.161, respectively, all P < 0.001) and no correlation of NLR with age (P = 0.205) was found.

Table 3

Correlation between NLR and clinicopathological characteristics
	Spearman correlation	P value
Age	0.031	0.205
CEA	0.157	< 0.001
CA19-9	0.173	< 0.001
CA72-4	0.161	< 0.001

Parameters are grouped by optimal cutoff value. Multiple logistic regression analysis showed that younger age (OR: 0.68, 95% CI: 0.547–0.844, P < 0.001), higher NLR (OR: 2.858, 95% CI: 2.295–3.559, P < 0.001), higher CEA (OR: 2.108, 95% CI: 1.671–2.661, P < 0.001), higher CA199 (OR: 1.844, 95% CI: 1.466–2.32, P < 0.001), higher CA724 (OR: 2.348, 95% CI: 1.851–2.978, P < 0.001) were independent risk factors for GC metastasis (Table 4).

Table 4

Univariate and multivariate analyses of variables for GC metastasis
	Univariate analysis			Multivariate analysis
	Odds ratio	95% CI	P value	Odds ratio	95% CI	P value
Age, years
<60 vs. ≥60	0.739	0.609–0.898	0.002	0.68	0.547–0.844	< 0.001
NLR
Low vs. high	3.375	2.748–4.145	< 0.001	2.858	2.295–3.559	< 0.001
CEA
Low vs. high	3.026	2.455–3.729	< 0.001	2.108	1.671–2.661	< 0.001
CA199
Low vs. high	2.813	2.289–3.455	< 0.001	1.844	1.466–2.32	< 0.001
CA724
Low vs. high	3.385	2.722–4.211	< 0.001	2.348	1.851–2.978	< 0.001

In our current study, we investigated the relationship between NLR and GC metastasis. Our study illustrated that peripheral blood NLR can more effectively predict GC metastases, including peritoneal, hepatic and osseous metastases, compared to CEA, CA19-9 and CA72-4. As a routine laboratory test, non-invasiveness and high diagnostic efficiency makes NLR a novel GC marker to assist clinicians in evaluating and diagnosing GC metastasis.

Tumor-associated persistent inflammatory environment is induced by continuous cell renewal and proliferation[15]. Through crosstalk between malignant and non-malignant cells, the inflammatory tumor microenvironment ultimately promotes tumor progression and metastasis[4]. This driving force is derived from inflammatory-derived survival, growth, and pro-angiogenic factors and from extracellular matrix (ECM)-modifying enzymes that promote angiogenesis, invasion, and metastasis[16]. On the other hand, inflammation suppresses antitumor immune responses, which help tumors evade host immunosurveillance[17]. Tumor-associated neutrophils suppress T-cell’s function in a PD-L1-dependent fashion, and, in doing so, contribute to the GC progression in vitro and in vivo[18]. Changes in circulating neutrophils are also reflected in neutrophil infiltration of the tumor environment[19]. This enlightens us that the level of circulating neutrophils in tumor patients may reflect tumor metastasis status. In fact, circulating tumor-associated neutrophils in advanced cancer patients contributes to the circulating tumor cell survival by suppressing peripheral leukocyte activation. As the tumor progresses, circulating neutrophils gradually increase and are converted into tumorigenic tumor-associated neutrophils, characterized by overexpression of CCL12, CXCL2 and Arg1 relative to naive neutrophils[20]. Neutrophils can also form a protective layer around circulating tumor cells to promote tumor metastasis[21]. These findings may have implications regarding the role of neutrophils in tumor metastasis prediction and tumor therapy.

Lymphocytes are part of cell-mediated immunity and play an important role in host anticancer defense mechanisms. Impaired lymphocyte function and reduced lymphocyte counts have been implicated in various cancers[22]. Perioperative lymphopenia is associated with poor prognosis in gastric cancer[23], [24]. Mounting evidence demonstrated that both absolute lymphocytes counts (ALC) in peripheral blood and tumor-infiltrating lymphocytes (TIL) are associated with tumor progression. Low TIL is associated with poor prognosis in esophageal squamous cell carcinoma. Furthermore, ALC in peripheral blood is positively correlated with TIL[25]. However, in a breast cancer study, ALC showed a negative correlation with TIL[26]. More research is needed to demonstrate the relationship between ALC and TIL.

Given that tumor patients are often accompanied by increased neutrophils and decreased lymphocytes, the predictive and prognostic role of NLR in tumors has been extensively studied. Most previous studies have either focused on high NLR as a useful predictor of long-term prognosis cancer patients or explored the role of NLR in the assessment of lymph node metastasis[11], [14], [27]-[30]. Less attention has been paid to the predictive role of NLR in distant metastasis. NLR has been reported to be an effective predictor of distant metastasis after radical surgery for pancreatic ductal adenocarcinoma[21]. Nizhen Xu et al demonstrated that elevated NLR is associated with a higher risk of metastasis in thyroid cancer patients[31]. Although the role of NLR in distant metastasis in GC patients has been reported, researchers did not compare the diagnostic efficacy of NLR with traditional tumor markers[32]. In the present study, we found that NLR was comparable or even superior to tumor markers in predicting distant metastases. The optimal cut-off of NLR were determined to be 2.91 with a sensitivity of 48.5% and a specificity of 76.3%. In sub-group analysis (peritoneal metastases, osseous metastases and liver metastases), the diagnostic efficacy of combined NLR and GC markers was significantly higher than that of combined GC markers. Both univariate and multivariate analyses indicated that high NLR was associated with high risk of tumor metastasis. Cancer patients with elevated NLR, especially advanced patients, should be alert to tumor metastasis, especially the occurrence of micro-metastases. Further studies should be conducted to determine whether detection and targeting of neutrophils can improve gastric cancer prognosis and benefit clinical treatment.

In conclusion, our findings suggest that NLR is helpful in predicting the presence of distant metastases in GC patients. Therefore, physicians should pay more attention to patients with NLR > 2.91, and then conduct further examinations to detect metastases as early as possible.

4.1. Patients

We collected the clinical data in The First Affiliated Hospital of Xi’an Jiaotong University between December 2,010 and December 2,018. Patients were excluded if they met one of the following criteria: (1) concurrent or secondary to other malignancies; (2) Infection; (3) Hematological disease or blood transfusion within the past 3 months; (4) No pre-treatment laboratory data. All patients had pretreatment hematological values and conventional GC biomarkers. At last, 1,667 patients first diagnosed with GC patients were enrolled in our study. Data evaluated included age at diagnosis, preoperative complete blood counts, Carcinoembryonic antigen (CEA), Carbohydrate antigen 19 − 9 (CA19-9) and Carbohydrate antigen 72 − 4 (CA72-4). Informed consent was obtained from all subjects and/or their legal guardian(s). All methods were performed in accordance with the relevant guidelines and regulations. This study was approved by the Ethics Committee of First Affiliated Hospital of Xi'an Jiaotong University.

4.2. Statistical analysis

We divided patients into metastatic (N = 743) and non-metastatic (N = 924) groups according to whether GC has metastasized or not. Counting variables are expressed as frequency (percentage) and compared using the Chi-square test or Fisher exact test. Non-normal continuous variables are expressed as the median [interquartile range (IQR)] and compared with log-rank tests, while continuous normal variates were presented as mean ± standard deviation and compared using Student's t-tests. The optimal cut-off values for NLR and GC biomarkers were obtained by ROC analyses. The predicted probability of the joint ROC curve analysis is obtained by binary logistic regression. Area under ROC (AUC) were compared using DeLong's test. We analyzed the correlation of NLR and other clinical indicators by Spearman’s correlation. Multiple logistic regression was performed to assess the relationship between explanatory variables and GC metastasis.

Statistical analysis and plotting were performed with IBM SPSS Statistics version 20.0 RRID:SCR_016479. DeLong's test was performed using MedCalc version 19.4.1 RRID:SCR_015044. 2-sided P < 0.05 were considered statistical significantly.

Author Contributions

XZ and XW wrote the main manuscript text. All authors reviewed the manuscript.

Competing interests

The authors declare no potential conflicts of interest.

Acknowledgements

Thanks to Professor Gang Tian from the First Affiliated Hospital of Xi'an Jiaotong University for her guidance on our research.

Data Availability

The data generated in this study are available upon request from the corresponding author.

Cao, M., Li, H., Sun, D. & Chen, W. Cancer burden of major cancers in China: A need for sustainable actions. Cancer Commun (Lond). 40, 205–210 (2020).
Biagioni, A. et al. Update on gastric cancer treatments and gene therapies. Cancer Metastasis Rev. 38, 537–548 (2019).
Singh, R., Mishra, M. K. & Aggarwal, H. Inflammation, Immunity, and Cancer. Mediators Inflamm. 2017, 6027305 (2017).
Grivennikov, S. I., Greten, F. R. & Karin, M. Immunity, inflammation, and cancer. Cell. 140, 883–899 (2010).
Wu, L., Saxena, S. & Singh, R. K. Neutrophils in the Tumor Microenvironment. Adv Exp Med Biol. 1224, 1–20 (2020).
Wang, T. T. et al. Tumour-activated neutrophils in gastric cancer foster immune suppression and disease progression through GM-CSF-PD-L1 pathway. Gut. 66, 1900–1911 (2017).
Jiang, Y., Xu, H., Jiang, H., Ding, S. & Zheng, T. Pretreatment neutrophil-lymphocyte count ratio may associate with gastric cancer presence. Cancer Biomark. 16, 523–528 (2016).
Jin, J., Yang, L., Liu, D. & Li, W. Association of the neutrophil to lymphocyte ratio and clinical outcomes in patients with lung cancer receiving immunotherapy: a meta-analysis. BMJ Open. 10, e035031 (2020).
Tang, H. et al. Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Colorectal Liver Metastasis: A Systematic Review and Meta-Analysis. PLoS One. 11, e0159447 (2016).
Magdy, M., Hussein, T., Ezzat, A. & Gaballah, A. Pre-treatment Peripheral Neutrophil-Lymphocyte Ratio as a Prognostic Marker in Gastric Cancer. J Gastrointest Cancer. 50, 763–768 (2019).
Aoyama, T. et al. Pretreatment Neutrophil-to-Lymphocyte Ratio Was a Predictor of Lymph Node Metastasis in Endometrial Cancer Patients. Oncology. 96, 259–267 (2019).
Zhu, G. et al. Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio Cannot Predict Lymph Node Metastasis and Prognosis in Patients with Early Gastric Cancer: a Single Institution Investigation in China. Curr Med Sci. 38, 78–84 (2018).
Lou, N. et al. A novel scoring system associating with preoperative platelet/lymphocyte and clinicopathologic features to predict lymph node metastasis in early gastric cancer. J Surg Res. 209, 153–161 (2017).
Xia, X. et al. Predictive value of neuron-specific enolase, neutrophil-to-lymphocyte-ratio and lymph node metastasis for distant metastasis in small cell lung cancer. Clin Respir J. 14, 1060–1066 (2020).
Schäfer, M. & Werner, S. Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol. 9, 628–638 (2008).
Mantovani, A., Allavena, P., Sica, A. & Balkwill, F. Cancer-related inflammation. Nature. 454, 436–444 (2008).
Greten, F. & Grivennikov, S. Inflammation and Cancer: Triggers, Mechanisms, and Consequences. Immunity. 51, 27–41 (2019).
Li, S. et al. Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells. J Exp Clin Cancer Res. 38, 6 (2019).
Rosales, C. Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? Front Physiol. 9, 113 (2018).
Zhang, J. et al. Circulating tumor-associated neutrophils (cTAN) contribute to circulating tumor cell survival by suppressing peripheral leukocyte activation. Tumour Biol. 37, 5397–5404 (2016).
Tao, L. et al. Neutrophils assist the metastasis of circulating tumor cells in pancreatic ductal adenocarcinoma: A new hypothesis and a new predictor for distant metastasis. Medicine. 95, e4932 (2016).
Matsuzaki, J. et al. Tumor-infiltrating NY-ESO-1-specific CD8 + T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A. 107, 7875–7880 (2010).
Saito, H. et al. Prognostic Significance of Pre- and Postoperative Lymphocyte Counts in Patients with Gastric Cancer. Dig Surg. 36, 137–143 (2019).
Park, S. J. et al. Association between absolute lymphocyte count and overall mortality in patients with surgically resected gastric cancer. Korean J Intern Med. 36, 679–688 (2021).
Zhu, Y. et al. Prognostic significance of the lymphocyte-to-monocyte ratio and the tumor-infiltrating lymphocyte to tumor-associated macrophage ratio in patients with stage T3N0M0 esophageal squamous cell carcinoma. Cancer Immunol Immunother. 66, 343–354 (2017).
Lee, K. H. et al. The prognostic and predictive value of tumor-infiltrating lymphocytes and hematologic parameters in patients with breast cancer. BMC Cancer. 18, 938 (2018).
Yang, J. J. et al. Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: a meta-analysis. World J Gastroenterol. 21, 2807–2815 (2015).
Howard, R., Kanetsky, P. A. & Egan, K. M. Exploring the prognostic value of the neutrophil-to-lymphocyte ratio in cancer. Sci Rep. 9, 19673 (2019).
Moon, G., Noh, H., Cho, I. J., Lee, J. I. & Han, A. Prediction of late recurrence in patients with breast cancer: elevated neutrophil to lymphocyte ratio (NLR) at 5 years after diagnosis and late recurrence. Breast Cancer. 27, 54–61 (2020).
Wang, Y. et al. Tumor-Associated Neutrophils Can Predict Lymph Node Metastasis in Early Gastric Cancer. Front Oncol. 10, 570113 (2020).
Xu, N., Jian, Y., Wang, Y. & Tian, W. Evaluation of neutrophil-to-lymphocyte ratio and calcitonin concentration for predicting lymph node metastasis and distant metastasis in patients with medullary thyroid cancer. Mol Clin Oncol. 9, 629–634 (2018).
Mansour, R., Abu-Shawer, O., Lattouf, A., Sultan, H. & Al-Hussaini, M. Hematological Indices of Distant Metastases and Prognostic Nomogram in Gastro-Pancreatic and Biliary Tract Cancers. Cancer Manag Res. 12, 9775–9786 (2020).

No competing interests reported.

Supplementaryfile.pdf

Download PDF

Editorial decision: Major revision
19 May, 2022
Reviews received at journal
11 May, 2022
Reviewers agreed at journal
08 May, 2022
Reviewers invited by journal
06 May, 2022
Editor assigned by journal
06 May, 2022
Editor invited by journal
17 Mar, 2022
Submission checks completed at journal
17 Mar, 2022
First submitted to journal
14 Mar, 2022

You are reading this latest preprint version

Predictive Value of Neutrophil-To-Lymphocyte Ratio for Distant Metastasis in Gastric Cancer Patients

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

1. Introduction

2. Results

2.1. Patient's characteristics

2.2. NLR can more efficiently predict gastric cancer metastasis than tumor markers

3. Discussion

4. Material And Methods

4.1. Patients

4.2. Statistical analysis

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1