|Ahead of print publication
Preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are correlated with tumor–node–metastasis stages in patients with non-small cell lung cancer
Han Cheng1, Sandeep Bhushan1, Na Li2, Zongwei Xiao1, Ke Gao1
1 Department of Cardiothoracic Surgery, Chengdu Second People's Hospital, Sichuan University, Chengdu, China
2 Department of Oncology, West China Fourth Hospital, Sichuan University, Chengdu, China
|Date of Submission||22-Mar-2021|
|Date of Decision||18-May-2021|
|Date of Acceptance||30-May-2021|
|Date of Web Publication||15-Oct-2021|
Department of Cardiothoracic Surgery, Chengdu Second People's Hospital, Chengdu 610017
Source of Support: None, Conflict of Interest: None
Background: The aim of this study is to explore the value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for predicting the tumor–node–metastasis (TNM) stages in non-small cell lung cancer (NSCLC) patients.
METHODS: This retrospective study included 205 NSCLC patients receiving surgical treatment. We used receiver operating curve analysis to confirm the optimal cutoff values of NLR and PLR.
RESULTS: The result showed that the thresholds for NLR and PLR were 1.8 and 103.59, respectively. NLR (P = 0.037; relative risk (RR), 3.027; 95% confidence interval (CI): 1.608–8.581) and PLR (P = 0.001; RR, 3.662; 95% CI: 1.342–9.992) were risks factors in predicting advanced TNM stages (Stage III/IV, all P < 0.05). In addition, NLR with T stage- and N stage-dependent increase may be a potential and independent predictive marker for T and N stage (all P < 0.05); the PLR was identified as a marker for T stage (P = 0.028) but not for N stage. Furthermore, we investigated the combination of NLR and PLR (CNP). A risk stratification based on CNP index was carried out as follows: low risk (NLR ≤1.8 and PLR ≤ 103.59), intermediate risk (either NLR >1.8 or PLR > 103.59), and high risk (both NLR >1.8 and PLR >103.59). The probabilities for developing advanced TNM stage were 6.4% for low, 20.4% for intermediate, and 47.1% for high-risk group (P < 0.001).
Conclusion: The levels of preoperative NLR and PLR were capable of indicating advanced TNM stages. According to the CNP index, patients were divided into three risk groups with different significance.
Keywords: Neutrophil-to-lymphocyte ratio, non-small cell lung cancer, platelet-to-lymphocyte ratio, tumor–node–metastasis stage
|How to cite this URL:|
Cheng H, Bhushan S, Li N, Xiao Z, Gao K. Preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are correlated with tumor–node–metastasis stages in patients with non-small cell lung cancer. J Can Res Ther [Epub ahead of print] [cited 2022 Jan 21]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=328255
| > Introduction|| |
Lung cancer is one of most aggressive malignancy and it is a leading cause of cancer-related death worldwide, with the highest morbidity and mortality rates among all cancers. Among a series of pathological genres, non-small cell lung cancer (NSCLC) accounts for approximately 85% and small-cell lung cancer consumes nearly 13% of overall lung cancer cases. In spite of advances in diagnosis and treatment of lung cancer have been accomplished, the prognosis is poor, with an overall 5 year survival rate of ~18%.
Currently, the tumor–node–metastasis (TNM) staging system is a guideline that offers helpful information for clinical treatments and predicting prognosis in lung cancer. The system classified patients according to the characteristics of the tumor itself, regional lymph nodes, and potentially metastatic sites. It is designed to classify patients with similar prognosis into the same stage group. Preoperative imaging evaluation of the TNM staging is an important factor in determining the availability of surgery. Computed tomography (CT) is the most commonly used to confirm the stage; however, in some cases, visualization of the tumors is not definitive because they are atypical. The evaluation of local invasion, intravascular diffusion, and lymph node metastasis is likely to be imprecise. Consequently, patients with the same preoperative TNM staging may have a different pathological stage after surgery. In addition to CT, positron emission tomography/CT (PET/CT) is used for early diagnosis and evaluation of malignancy occasionally. However, this technology is often difficult to implement widely in the public because of funding limitations. Therefore, a readily low-cost and simple test is needed to identify different American Joint Commission on Cancer (AJCC) TNM stages in lung cancer patients.
Previous studies have demonstrated that systemic inflammation plays an important part in malignancy occurrence and development by regulating tumor microenvironment., An increasing amount of evidence has suggested that the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are possible makers of systemic inflammation and immune response., Dharmapuri et al. reported that low NLR and PLR potentially predict better results for immunotherapy.
Accurate staging is not only related to prognosis, but also contributes to determine the most appropriate treatment. Although a number of retrospective studies have estimated the prognostic significance of baseline NLR and PLR,,,,,,,, in lung cancer as well as other malignancies, the role of systemic inflammation involved in stages of malignancy development is rarely studied in lung cancer., Furthermore, the combination of NLR and PLR (CNP) was demonstrated to be better predictors of survival in patients with esophageal neoplasms and NSCLC,, but its value in predicting cancer stages has never been studied. Therefore, the main objective of this study was to investigate the value of the NLR, PLR, and CNP index for providing useful information for prediction of disease stages in NSCLC.
| > Methods|| |
Patients and controls
A total of 205 consecutive NSCLC cancer patients, who were diagnosed according to pathology results after surgical treatment at our department between January 2016 and July 2019, were included in this study. The inclusion criterion for this study was histologically diagnosed with NSCLC. The exclusion criteria were as follows: Signs of inflammation, autoimmune diseases, previous malignancies, hematonosis or receipt of anticancer treatment prior to surgery. As a control group, we reviewed the records of 91 individuals with benign pulmonary nodules experiencing homochronous operation at the hospital, including hamartoma, sclerosing pneumocytoma, organizing pneumonia, and pulmonary granulomas.
The present study was approved by the Ethics Committee of hospital. Written informed consent was obtained from every participant according to the institutional guidelines of hospital when they were enrolled.
The clinical parameters including age, gender, smoking history, and circulating blood counts were ordinarily detected within 7 days before surgery. The TNM staging is confirmed according to the eighth edition of the AJCC guidelines after operation. The NLR was calculated by dividing the absolute neutrophil count (ANC) by the absolute lymphocyte count (ALC); the PLR was calculated by dividing the absolute platelet count by ALC. Patients were divided into three groups based on CNP: low risk, normal NLR and PLR; intermediate risk, high NLR or high PLR; and high risk, high NLR and high PLR.
The optimal cutoff values of NLR and PLR were calculated using receiver operating curve (ROC) analysis. Categorical variables were analyzed using Chi-square test. Differences of NLR and PLR between patients and controls were evaluated by t-test for variables with normal distribution or by Mann–Whitney U-test for abnormally distributed variables. The association of NLR and PLR with TNM stages was evaluated by Kruskal–Wallis test followed by a post hoc test. A multivariate regression analysis was performed to analyze the factors that associated to TNM stages. Statistical significances were considered if the two-tailed P < 0.05. Statistical analyses were performed using SPSS software, version 22.0 (IBM Corp, Armonk, NY).
| > Results|| |
Patient characteristics are listed in [Table 1]. The median age was 61 years (range = 37–78 years). There was a male predominance. Evaluation of TNM stages was as follows: 66 patients (32.2%) presented with stage I disease, 76 patients (37.1%) presented with Stage II disease, 58 patients (28.3%) presented with Stage III disease, and only 5 patients (2.4%) were classified into Stage IV. According to the TNM stage classification, 34 patients (16.6%) presented with deep tumor infiltration (T stage > 2), 71 patients (34.6%) had lymphatic invasion (N stage > 0), and 5 patients (2.4%) exhibited distant metastasis (M stage = 1). The preoperative NLR and PLR levels in identifying patients with advanced TNM stage (Stage III/IV) NSCLCs were shown as ROC curve. The optimal cutoff values for NLR and PLR calculated by the ROC analysis were 1.8 (area under the curve [AUC] value 0.722, 95% confidence interval (CI): 0.650–0.793, P < 0.001) and 103.59 (AUC 0.648, 95% CI: 0.568–0.728, P = 0.001, respectively [Table 1] and [Figure 1].
|Table 1: Characteristics of patients with non-small cell lung cancer and controls|
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|Figure 1: Receiver operating curve for determining the optimal cutoff value in in identifying patients with advanced tumor–node–metastasis stage for neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio|
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Comparison of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in non-small cell lung cancer patients and controls
205 NSCLC patients and 91 controls were subsequently enrolled in the present study. As demonstrated in [Table 1], NSCLC patients had higher WBC and ALC levels when compared to that of controls (all P < 0.05). However, no significant difference was found in the levels of NLR and PLR between the patients and controls [Figure 2]a and [Figure 2]b.
|Figure 2: Neutrophil-to-lymphocyte ratio in patients with non-small cell lung cancer and controls (a). Platelet-to-lymphocyte ratio in patients with nonsmall-cell lung cancer and controls (b)|
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Difference of patients' characteristics classified by neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio
Comparisons of characteristics between the patients with low NLR (NLR ≤1.8) and high NLR (NLR >1.8) levels are displayed in [Table 2]. Significant differences were found regarding TNM stage (P < 0.001), T stage (P < 0.001), and N stage (P < 0.001). Compared to the low NLR group, patients in the high NLR group were more likely to have advanced TNM stages (Stage III/IV), suffer from deep tumor infiltration (T stage > 2), and present with lymphatic invasion (N stage > 0). However, no significant difference was found between the two groups regarding gender, smoke history, and distant metastasis (M stage) [Table 2].
|Table 2: Difference of patients' characteristics classified by neutrophil-to-lymphocyte ratio|
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Comparisons of characteristics between the patients with low PLR (PLR ≤ 103.59) and high PLR (PLR > 103.59) are displayed in [Table 3]. Compared to the low PLR group, patients in the high PLR group were more likely to have advanced TNM stages (P < 0.001), suffer from deep tumor infiltration (P = 0.016), and present with lymphatic invasion (P = 0.001). However, no significant difference was found in age, gender, smoke history, and distant metastasis [Table 3].
|Table 3: Difference of patients' characteristics classified by platelet-to-lymphocyte ratio|
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According to CNP index, patients were stratified into three risk groups: low risk (NLR ≤ 1.8 and PLR ≤ 103.59), intermediate risk (either NLR >1.8 or PLR > 103.59), and high risk (both NLR > 1.8 and PLR > 103.59). Clinical features of patients in the three risk groups were compared [Table 4]. Significant differences were observed in TNM stages (P < 0.001), T stages (P = 0.002), and N stages (P < 0.001). The higher the CNP index, the later the staging of NSCLCs. The proportions of patients with TNM stage III-IV in low-risk, intermediate-risk, and high-risk groups were 6.4%, 20.4%, and 47.1%, respectively. Likewise, the percentages of patients with T stage 3-4 in different risk groups (from low risk to high risk) were 2.1%, 14.8%, and 25%, respectively. The lymphatic metastasis rate in the group of patients with low, intermediate, and high CNP index were 14.9%, 25.9%, and 49%, respectively [Table 4].
|Table 4: Difference of patients' characteristics classified by CNP index|
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Association of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with tumor–node–metastasis stages in non-small cell lung cancer patients
In present study, we further analyzed the relationship between NLR and PLR with tumor TNM and independent TNM stages [Figure 3]. There were significant interactions between increased levels of NLR with elevated TNM stages P < 0.001, [Figure 3]a, T stages P < 0.001, [Figure 3]c, and N stages P < 0.001, [Figure 3]e. Associations between increased levels of PLR and raised TNM stages P = 0.015, [Figure 3]b and T stages P = 0.028, [Figure 3]d observed. No significant difference of PLR was observed in N stages (P = 0.083). Neither NLR (P = 0.582) nor PLR (P = 0.693) showed any significant association with the development of M stages.
|Figure 3: Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were compared with tumor–node–metastasis and independent tumor–node–metastasis stages in patients with non-small cell lung cancer. Significant associations were identified between tumor–node–metastasis stage and neutrophil-to-lymphocyte ratio level (a) (P = 0.037), and between tumor–node–metastasis stage and platelet-to-lymphocyte ratio level (b) (P = 0.001). An increased neutrophil-to-lymphocyte ratio was intrinsically associated with T stage (c) and N stage (e) (all P < 0.05). (d) Significant difference was observed between T stage and platelet-to-lymphocyte ratio (P = 0.028). There was no differences were between M stages and neutrophil-to-lymphocyte ratio levels (g), or between N stage and platelet-to-lymphocyte ratio (f), or between M stage and platelet-to-lymphocyte ratio (h) (all P > 0.05)|
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Regression analysis was applied to the assessment of risk factors for TNM stages [Table 5]. In univariate analysis, increased level of NLR, PLR, and ANC and decreased ALC were risk factors for advanced TNM stages (TNM Stage III/IV). However, multivariate analysis demonstrated that only NLR (P = 0.037; relative risk (RR), 3.027; 95% CI: 1.608–8.581) and PLR (P = 0.001; RR, 3.662; 95% CI: 1.342–9.992) were in capable of predicting progressive stages of disease [Figure 3] and [Table 5].
|Table 5: Predictive features affecting tumor–node–metastasis stages (tumor–node–metastasis Stage I/II vs. Stage III/IV) In univariate and multivariate analysis|
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| > Discussion|| |
Accurate clinical TNM staging is critical to decide whether surgery is suitable for implementation in most malignancies. PET/CT is an imaging examination that reflects the gene, molecule, metabolism, and functional state of the cancer. A recent study has shown the potential of CT radiomics to help recognizing the underlying gene expression patterns in lung and head-and-neck Cancer. On account of the high cost of PET/CT examination, it is not considered as a routine preoperative examination in NSCLCs. Consequently, contrast-enhanced CT is the most common preoperative examination used to evaluate the AJCC TNM stages in NSCLCs. The criteria for N staging are based on the size and shapes of lymph nodes, and the received tumor invasion standard is that lymph nodes are >1 cm, which is not precise for many benign diseases may cause lymphadenovarix., Hence, contrast-enhanced CT has its limitations in preoperative staging assessment.
Systemic inflammation has long been proven to be associated with the occurrence and development of cancer by promoting tumor angiogenesis and cancer cell proliferation and by affecting the tumor response to systemic treatment in a number of studies.,,, As is reported, neutrophils, platelets, and lymphocytes participate a lot in the tumor-related inflammation and immunology. Neutrophils produce a series of cytokines, including interleukin 1 (IL-1), IL-8, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α, which may contribute to a microenvironment that promotes tumor invasion. Thus, an elevation of neutrophils may lead to negative impacts on the tumor-bearing host, bringing about an advanced TNM stage. Lymphocytes are mediators of antibody-dependent cell-mediated cytotoxicity and are indicators of host immune activity., Elevated tumor infiltrating lymphocytes are related to prolonged survival of cancer patients and it increases lymphocyte counts and function which promote cancer development and progression. The increase in NLR presents high anti-inflammatory activity in patients with a high level of ANC and a low value of ALC. Platelets participate in the systematic inflammatory through reactive thrombocytosis, which is regulated by IL-6. Platelets are able to regulate inflammatory cells such as neutrophils, promote the adhesion of their own to lymphocytes in the inflammatory reaction, and accelerate the progression of cancer as well. The prognostic values of NLR and PLR serving as inflammation-based biomarkers have been widely studied in various cancers,,,,,,,,, however, the roles of the two parameters in cancer staging were rarely reported.,,,
The abnormal NLR and PLR may result in an unbalance of tumor growth and a poor prognosis. Tumor cells may exhibit uncontrolled growth and rapid proliferation or even migrate to a more appropriate microenvironment in order to maintain growth of their own during the unbalance. The elevation of NLR and PLR showed isochronous increase in neutrophil and platelet counts and a relative decrease in lymphocyte counts, suggesting that neutrophil and platelet-dependent inflammatory response increased and lymphocyte-mediated antitumor immune response decreased.
The optimal values of NLR and PLR were unclear. Huang et al. first described the role of the two markers in evaluating regional nodal involvement rate. The combination of enhanced contrast CT and NLR was demonstrated to be valuable in exploring the lymph nodal metastasis in patients with NSCLC, and the result revealed that the combination of NLR with a cutoff value of 3.87 and enhanced contrast CT showed a higher efficiency in predicting nodal metastasis compared to the two parameters separately, whereas PLR with a cutoff value of 140.83 did not show significant effect in diagnosing nodal involvement. Xu et al. reported that high NLR and PLR levels were associated with advanced TNM stages and that PLR and NLR were independent predictors for T and N stages, respectively. A research that predicted papillary thyroid cancer staging showed that NLR at a threshold of 2 was positively correlated with the AJCC TNM stage. Huang et al. carried out a study that NLR at a threshold of 2.75 and PLR at a cutoff value of 172.25 independently predicted different AJCC T stages in hilar cholangiocarcinoma. In this study, we conducted an ROC method suggesting that the most discriminatory threshold value for NLR was 1.8, which is relatively consistent with previous study accomplished by Gong et al. Both univariate and multivariate analyses demonstrated that the NLR at this cutoff value and PLR at a threshold of 103.59 were sensitive factors for identifying NSCLC patients with advanced TNM stages. Our data discovered significant differences in staging between the high and low NLR and PLR groups [Figure 3]. Patients with high NLR or PLR levels were more likely to have advanced TNM stages, suffer from deep tumor infiltration, and present with lymphatic invasion when compared to those with low NLR or PLR level, respectively. Those results suggested that both neutrophil- and platelet-dependent inflammation responses were actively participated in the different stages of cancer progression. However, no significant difference was found between the high and low NLR or between the high and low PLR groups regarding M stage. This may be partially explained by the reason that distant metastasis occurs in a quite small proportion of patients, with a percentage of only 2.4% of all cases.
In present study, we stratified patients into three risk categories with significantly different proportions according to CNP index. The percentages of patients with advanced TNM stage in low-, intermediate-, and high-risk groups were 6.4%, 20.4%, and 47.1%, respectively (P < 0.001); the percentages of patients with deep tumor infiltration in the three risk groups (from low to high risk) were 2.1%, 14.8%, and 25%, respectively (P = 0.002); and the lymphatic metastasis rate in the group of patients with low-, intermediate-, and high-CNP index were 14.9%, 25.9%, and 49%, respectively (P < 0.001). Those results demonstrated that patients simultaneously have high NLR and PLR level readily had disadvantageous characteristics in terms of advanced TNM stage, deep tumor infiltration, and lymph node metastasis. Consequently, for patients with high NLR and PLR, systematic nodal dissection might be preferably selected instead of regional nodal dissection.
Previous studies reported that the levels of NLR and PLR were higher in malignancies than that of in the healthy controls;, however, no comparison of NLR and PLR in patients with NSCLCs and pulmonary benign nodules was reported. We conducted this study to compare the preoperative values of the two parameters in patients with NSCLCs and cases with pulmonary benign nodules. The result showed that no significant differences for NLR or PLR level were found between patients and controls.
The present study had limitations including that it was a retrospective and single-center study with certain bias in enrolling participants and that a relative limited number of patients were included, particularly, only a few M1 stage patients (2.4%) were incorporated. Therefore, further studies with larger sample and multicenter are indispensable to confirm the preliminary results.
| > Conclusion|| |
In conclusion, the present study demonstrated that the levels of preoperative NLR and PLR are independently correlated with the tumor stages in NSCLC patients. Using the CNP index, patients were divided into three different risk groups with advanced stages prior to operation: low (NLR ≤ 1.8 and PLR ≤ 103.59), intermediate (NLR >1.8 or PLR > 103.59), and high risk (NLR >1.8 and PLR > 103.59). These observations may provide useful insight for clinical practice for making an appropriate treatment regimen.
The authors are thankful to the medical, nursing, and clinical laboratory staff in Chengdu second people's hospital (Sichuan, China) for their commendable contributions to this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al
. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86.
Andrade FM, Mourad OM, Judice LF. The revised tumor-node-metastasis staging system for lung cancer: Changes and perspectives. J Bras Pneumol 2010;36:617-20.
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell 2011;144:646-74.
Lorente D, Mateo J, Templeton AJ, Zafeiriou Z, Bianchini D, Ferraldeschi R, et al
. Baseline neutrophil-lymphocyte ratio (NLR) is associated with survival and response to treatment with second-line chemotherapy for advanced prostate cancer independent of baseline steroid use. Ann Oncol 2015;26:750-5.
Faria SS, Fernandes PC Jr., Silva MJ, Lima VC, Fontes W, Freitas-Junior R, et al
. The neutrophil-to-lymphocyte ratio: A narrative review. Ecancermedicalscience 2016;10:702.
Marchioni M, Primiceri G, Ingrosso M, Filograna R, Castellan P, De Francesco P, et al
. The clinical use of the neutrophil to lymphocyte ratio (NLR) in urothelial cancer: A systematic review. Clin Genitourin Cancer 2016;14:473-84.
Dharmapuri S, Özbek U, Lin JY, Sung M, Schwartz M, Branch AD, et al
. Predictive value of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in advanced hepatocellular carcinoma patients treated with anti-PD-1 therapy. Cancer Med 2020;9:4962-4970.
Wu Y, Chen Y, Yang X, Chen L, Yang Y. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were associated with disease activity in patients with systemic lupus erythematosus. Int Immunopharmacol 2016;36:94-9.
Lan H, Zhou L, Chi D, Zhou Q, Tang X, Zhu D, et al
. Preoperative platelet to lymphocyte and neutrophil to lymphocyte ratios are independent prognostic factors for patients undergoing lung cancer radical surgery: A single institutional cohort study. Oncotarget 2017;8:35301-10.
Zhang T, Jiang Y, Qu X, Shen H, Liu Q, Du J. Evaluation of preoperative hematologic markers as prognostic factors and establishment of novel risk stratification in resected pN0 non-small-cell lung cancer. PLoS One 2014;9:e111494.
Zhou DS, Xu L, Luo YL, He FY, Huang JT, Zhang YJ, et al
. Inflammation scores predict survival for hepatitis B virus-related hepatocellular carcinoma patients after transarterial chemoembolization. World J Gastroenterol 2015;21:5582-90.
Wang X, Teng F, Kong L, Yu JM. Pretreatment neutrophil-to-lymphocyte ratio as a survival predictor for smallcell lung cancer. Onco Targets Ther 2016;9:5761-70.
Unal D, Eroglu C, Kurtul N, Oguz A, Tasdemir A. Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis? Asian Pac J Cancer Prev 2013;14:5237-42.
Pinato DJ, Shiner RJ, Seckl MJ, Stebbing J, Sharma R, Mauri FA. Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer. Br J Cancer 2014;110:1930-5.
Sanchez-Salcedo P, de-Torres JP, Martinez-Urbistondo D, Gonzalez-Gutierrez J, Berto J, Campo A, et al
. The neutrophil to lymphocyte and platelet to lymphocyte ratios as biomarkers for lung cancer development. Lung Cancer 2016;97:28-34.
Kos M, Hocazade C, Kos FT, Uncu D, Karakas E, Dogan M, et al
. Prognostic role of pretreatment platelet/lymphocyte ratio in patients with non-small cell lung cancer. Wien Klin Wochenschr 2016;128:635-40.
Xu F, Xu P, Cui W, Gong W, Wei Y, Liu B, et al
. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may aid in identifying patients with non-small cell lung cancer and predicting TumorsMetastasis stages. Oncol Lett 2018;16:483-90.
Huang C, Yue J, Li Z, Li N, Zhao J, Qi D. Usefulness of the neutrophil-to-lymphocyte ratio in predicting lymph node metastasis in patients with non-small cell lung cancer. Tumour Biol 2015;36:7581-9.
Feng JF, Huang Y, Liu JS. Combination of neutrophil lymphocyte ratio and platelet lymphocyte ratio is a useful predictor of postoperative survival in patients with esophageal squamous cell carcinoma. Onco Targets Ther 2013;6:1605-12.
Wu G, Yao Y, Bai C, Zeng J, Shi D, Gu X, et al
. Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients. Thorac Cancer 2015;6:275-87.
Aerts HJ, Velazquez ER, Leijenaar RT, Parmar C, Grossmann P, Carvalho Sr RT, et al
. Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach [published correction appears in Nat Commun. 2014;5:4644.
Herth FJ, Ernst A, Eberhardt R, Vilmann P, Dienemann H, Krasnik M. Endobronchial ultrasound-guided transbronchial needle aspiration of lymph nodes in the radiologically normal mediastinum. Eur Respir J 2006;28:910-4.
Birim O, Kappetein AP, Stijnen T, Bogers AJ. Meta-analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in nonsmall cell lung cancer. Ann Thorac Surg 2005;79:375-82.
Takamochi K, Yoshida J, Murakami K, Niho S, Ishii G, Nishimura M, et al
. Pitfalls in lymph node staging with positron emission tomography in non-small cell lung cancer patients. Lung Cancer 2005;47:235-42.
Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010;140:883-99.
Wang H, Taverna D, Stram DO, Fortini BK, Cheng I, Wilkens LR, et al
. Genetic variation in the inflammation and innate immunity pathways and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2013;22:2094-101.
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: Integrating immunity's roles in cancer suppression and promotion. Science 2011;331:1565-70.
Shiels MS, Engels EA, Shi J, Landi MT, Albanes D, Chatterjee N, et al
. Genetic variation in innate immunity and inflammation pathways associated with lung cancer risk. Cancer 2012;118:5630-6.
McColl SR, Paquin R, Ménard C, Beaulieu AD. Human neutrophils produce high levels of the interleukin 1 receptor antagonist in response to granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha. J Exp Med 1992;176:593-8.
Weiner GJ. Rituximab: Mechanism of action. Semin Hematol 2010;47:115-23.
Kim DH, Baek JH, Chae YS, Kim YK, Kim HJ, Park YH, et al
. Absolute lymphocyte counts predicts response to chemotherapy and survival in diffuse large B-cell lymphoma. Leukemia 2007;21:2227-30.
Shimada H, Oohira G, Okazumi S, Matsubara H, Nabeya Y, Hayashi H, et al
. Thrombocytosis associated with poor prognosis in patients with esophageal carcinoma. J Am Coll Surg 2004;198:737-41.
Huang H, Wan X, Bai Y, Bian J, Xiong J, Xu Y, et al
. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of T stages in hilar cholangiocarcinoma. Cancer Manag Res 2019;11:5157-62.
Hu HJ, Jin YW, Zhou RX, Ma WJ, Yang Q, Wang JK, et al
. Clinical value of inflammation-based prognostic scores to predict the resectability of hyperbilirubinemia patients with potentially resectable hilar cholangiocarcinoma. J Gastrointest Surg 2019;23:510-7.
Gong W, Yang S, Yang X, Guo F. Blood preoperative neutrophil-to-lymphocyte ratio is correlated with TNM stage in patients with papillary thyroid cancer. Clinics (Sao Paulo) 2016;71:311-4.
Jia J, Zheng X, Chen Y, Wang L, Lin L, Ye X, et al
. Stage-dependent changes of preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in colorectal cancer. Tumour Biol 2015;36:9319-25.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]