Pre‑ and postoperative neutrophil and lymphocyte count and neutrophil‑to‑lymphocyte ratio in patients with colorectal cancer

  • Authors:
    • Katarzyna Jakubowska
    • Mariusz Koda
    • Wojciech Kisielewski
    • Luiza  Kańczuga‑Koda
    • Małgorzata Grudzińska
    • Waldemar Famulski
  • View Affiliations

  • Published online on: August 25, 2020     https://doi.org/10.3892/mco.2020.2126
  • Article Number: 56
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Abstract

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide. Patients with CRC are diagnosed based on various predictors, including performance status, clinicopathological factors and TNM classification. The aim of the present study was to analyze the neutrophil and lymphocyte counts, as well as the neutrophil‑to‑lymphocyte ratio (NLR) in pre‑ and postoperative blood samples of patients with CRC in correlation with specific anatomical variables and disease‑ free survival (DFS). The variables pre‑ and postoperative neutrophil count (preNEU and postNEU, respectively), lymphocyte count and NLR were significantly higher in cancer patients than those noted in healthy subjects (all P<0.001). PreNEU count correlated with tumor size, necrosis and tumor budding (R=0.204, P=0.014; R=0.189, P=0.023; R=‑0.174, P=0.036, respectively). Moreover, postNEU was associated only with the histological type (R=0.174; P=0.047). The PreLYMPH count was correlated with distant metastasis (R=‑0.153, P=0.046). PreNLR and postNLR were associated with the expression of various histological markers of disease progression. Analysis of DFS indicated that the postNEU count in the low group exhibited a tendency to lower DFS duration, although the results were not significant (P=0.055). In conclusion, the present study indicated a significant correlation between the factors analyzed in blood samples of CRC patients and the disease progression markers.

Introduction

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide (1). Currently, patients with CRC are diagnosed based on various predictors, including performance status, clinicopathological factors and TNM classification (2). Moreover, systemic immune response may be a useful determinant of the tumor stage (3). Certain studies have confirmed that immune system factors are actively involved in the development and invasion of CRC cells (4). These factors include the levels of serum white blood cells, the number of neutrophils, lymphocytes and platelets, and the expression levels of acute-phase proteins (5). It has also been demonstrated that high serum levels of acute-phase proteins, such as C-reactive protein (CRP), are significantly correlated with poor survival of patients with CRC (6). Rasic et al (7) demonstrated that the serum level of CRP was an independent predictor of the CRC stage. Yamamoto et al (8) indicated that the combination of pre- and postoperative CRP levels was predictive of the prognosis of CRC patients who underwent surgery. Recent studies suggested that the combination of the acute-phase factors and systemic whole-blood parameters, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index may have prognostic significance in the progression of CRC (9,10). Zhou et al (11) confirmed that patients with a higher postoperative NLR, neutrophil count and monocyte-to-lymphocyte ratio, PLR and systemic immune inflammation index, exhibited shorter progression-free survival. Moreover, it has been shown that a high NLR is a prognostic factor for poor survival in mismatch repair-proficient CRC subjects (12). In light of this evidence, neutrophil count, lymphocyte count and NLR were assessed in blood samples collected pre- and postoperatively from patients with CRC. These indices were analyzed in association with disease-free survival (DFS) and with specific clinicopathological variables.

Materials and methods

Patients

The medical records of 144 patients diagnosed with CRC (56 women and 88 men; mean age, 63 years; range, 32-86 years) were analyzed. The patients underwent surgery at the Department of Oncological Surgery, in the Comprehensive Cancer Center of Bialystok, between April 2014 and December 2016. All the patients were subjected to routine diagnostic laboratory examinations, such as electrocardiography, spirometry and arterial blood gas measurements, as well as X-ray imaging and computerized tomography of the chest. The clinical efficiency was assessed with the 5-point scale of Zubroda (World Health Organization) (13). The clinical staging of CRC was performed according to the TNM classification (2). The type of pre/postoperative therapy was selected on the basis of the current recommendations for CRC treatment. Patients diagnosed with neoplasms in the rectum (n=53) received preoperative therapy; specifically, they received radiotherapy (n=39), chemotherapy (n=7) and radiochemotherapy (n=7). A radiation dose of 25 Gy to the pelvic area was administered to the patients in fractions of 5 Gy over 1 week. Patients with tumors localized in other areas received neither inflammatory nor immunosuppressive therapy. The response to preoperative therapy was estimated according to the Response Evaluation Criteria in Solid Tumors v1.1(14). A total of 26 patients were diagnosed with stable disease and 27 with partial response to treatment. Histopathological examination of 4-µm sections stained with hematoxylin and eosin (cat. no. 468802128; POCH S.A.) was performed. The routine histopathological assessment of the sections took into consideration the type of tumor growth, tumor size, histological type and percentage of the mucinous component, grade of malignancy and pTNM stage. In addition, the presence of venous, lymphatic and perineural invasion was assessed, and specific features of lymph node invasion were characterized, such as the number of resected and invaded lymph nodes, the presence of micro- and macrometastases, invasion of the lymph node pouch (passage of cancer cells through the lymph node capsule and subsequent infiltration of the local fat tissue) and the presence of distant metastases. The methodology used was similar to that of our previous study (15).

The present study was performed according to the principles outlined in the Declaration of Helsinki for human experimentation and the protocol was approved by the Bioethics Committee of the Medical University of Bialystok (approval no. R-I-002/353/2016). Written informed consent was obtained from all participants.

Blood samples

Blood samples were obtained within 3 days prior to and following surgical treatment. Venous blood samples were also obtained from 42 healthy control subjects (21 women and 21 men; mean age, 45 years; range, 25-65 years). The differential white blood cell count was analyzed using the Sysmex XN-1000 apparatus (Sysmex Corporation) based on the manufacturer's protocol.

The absolute neutrophil and lymphocyte counts were measured prior to and following surgery. The NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. Receiver operating characteristic (ROC) curve analysis was used to investigate the cut-off values of the pre- and postoperative neutrophil count (preNEU/postNEU), lymphocyte count (preLYMPH/postLYMPH) and NLR (preNLR/postNLR). The significance of the correlations was evaluated by constructing ROC curves. The scores of neutrophil count/lymphocyte count/NLR were defined as 1 or 2 when patients exhibited low or high levels of the analyzed parameters, respectively, as determined in the blood samples collected pre- and postoperatively.

Follow-up data

The patients were followed up during the last 2-3 years. They were monitored by physical examination, colonoscopy and the measurement of the carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels. In addition, radiological imaging was performed, which included computerized tomography of the chest, abdomen and pelvis, bone scan and positron emission tomography scans. Local and distant recurrence was defined as pathological evidence of tumor spread in the region of the anastomosis (local recurrence) and/or the presence of cancer cells outside of the primary tumor at other sites, including the lungs, bones and brain (distant recurrence). These indices were confirmed by the aforementioned techniques.

Statistical analysis

Statistical analysis was conducted using the STATISTICA 12.0 program (Statsoft, Inc.). The Mann-Whitney U test was used to compare the differences between the groups. Correlations between the parameters were calculated by the Spearman's correlation coefficient tests. DFS was calculated from the date of diagnosis to the date of disease progression (local or distant relapse). DFS was estimated using Kaplan-Meier analysis and the survival curves were compared using log-rank tests. P<0.05 was considered to indicate a statistically significant difference.

Results

Estimation of cut-off values of neutrophil count, lymphocyte count and NLR

The preNEU and postNEU were significantly higher in cancer patients compared with those in healthy subjects (P≤0.001). Similarly, the preLYMPH/postLYMPH and preNLR/postNLR in the blood samples were significantly higher in cancer patients compared with those in healthy volunteers (both P≤0.001; Table I). The cut-off values of the preNEU and postNEU were 4.9 and 5.4, respectively (sensitivity and specificity: preNEU, 70.5 and 59.5%; and postNEU, 62.67 and 92.11%, respectively). The low preNEU group included 115 subjects, whereas the high group included 29 subjects. The low postNEU group included 91 patients and the high postNEU group included 53 patients. The cut-off values of the preLYMPH and postLYMPH were 1.9 and 1.6, respectively, with a sensitivity and specificity of 81.76 and 69.05% (preLYMPH) and of 65.79 and 81.63% (postLYMPH), respectively. The low preLYMPH group included 108 cases, whereas the high group included 36 cases. A total of 70 cases with low postLYMPH and 74 with high postLYMPH were observed. Moreover, the cut-off values of preNLR and postNLR were 2.5 and 3.3, respectively, with a sensitivity and specificity of 100% (Fig. 1A-F). The preNLR value was low in 99 cases and high in 45 cases. The low group of postNLR included 65 cases, whereas 79 cases were included in the high postNLR group.

Table I

ROC curve of pre- and postoperative neutrophil count, lymphocyte count and NLR.

Table I

ROC curve of pre- and postoperative neutrophil count, lymphocyte count and NLR.

 PreNEUPostNEUPreLYMPHPostLYMPHPreNLRPostNLR
Cut-off value4.95.41.91.62.53.3
AUC0.6900.8200.8140.7891.0001.000
Sensitivity (%)70.562.6781.7665.79100100
Specificity (%)59.592.1169.0581.63100100
Disease prevalence (%)77.779.879.175.678.977.8
P-value≤0.001≤0.001≤0.001≤0.001≤0.001≤0.001

[i] ROC, receiver operating characteristics; AUC, area under the ROC curve; preNEU, preoperative neutrophil count; postNEU, postoperative neutrophil count; preLYMPH, preoperative lymphocyte count; postLYMPH, postoperative lymphocyte count; preNLR, preoperative neutrophil-to-lymphocyte ratio; postNLR, postoperative neutrophil-to-lymphocyte ratio.

Correlation between neutrophil count, lymphocyte count, NLR and clinicopathological variables

PreNEU was correlated with tumor size, necrosis and tumor budding (R=0.204, P=0.014; R=0.189, P=0.023; and R=-0.174, P=0.036, respectively). Moreover, the postNEU value was significantly associated only with histological type (R=0.174, P=0.047). PreLYMPH was correlated with distant metastasis (R=-0.153, P=0.046). PreNLR was correlated with age and lymphatic invasion (R=-0.225, P=0.007; R=0.181, P=0.030; Table II). Moreover, postNLR was associated with specific variables of tumor progression, such as tumor growth, lymph node metastasis, number of invaded lymph nodes and invasion of the node pouch (R=0.212, P=0.016; R=0.200, P=0.023; R=0.175, P=0.047; and R=0.232, P=0.008, respectively; Table III). The results indicated no correlation between the analyzed parameters and preoperative treatment.

Table II

Correlation between neutrophil and lymphocyte count and clinicopathological characteristics.

Table II

Correlation between neutrophil and lymphocyte count and clinicopathological characteristics.

 Neutrophil count Lymphocyte count 
 Preoperative Postoperative Preoperative Postoperative 
ParametersLHP-valueLHP-valueLHP-valueLHP-value
Age, years
     <602414-0.1271618-0.1632711-0.0431322-0.095
     >6079270.12659370.06279260.55747480.279
Sex
     Female44100.14131210.03245110.1292131-0.073
     Male59310.09244340.71161260.12339390.403
Localization
     Right colon125-0.047107-0.123133-0.0537100.106
     Transverse colon320.587310.175430.539220.598
     Left colon122 103 120 85 
     Sigmoid colon156 128 166 911 
     Rectum5519 3631 5422 3037 
Tumor growth
     Expanding8233-0.0876146-0.03087310.03752560.131
     Infiltrative2150.2971490.7311960.6548140.134
Tumor size, cm
     <2.52040.2041380.011177-0.0261290.094
     2.5-5.071230.01450390.89471240.75640490.283
     >5.01211 128 186 812 
TNM stage
     1159-0.0862112-0.037299-0.0841319-0.091
     255120.30313140.6292080.31314140.299
     3204 2924 3119 2230 
     4713 125 261 116 
Adenocarcinoma type
     Mucinous component2232-0.05710150.174245-0.1079160.085
     Non-mucinous8160.49665400.04782320.20051540.331
Grade of malignancy
     297360.0217052-0.030100350.0215567-0.125
     3620.798530.726620.796530.153
pT stage
     1210.05212-0.04221-0.03421-0.049
     242130.52929200.62941130.68321270.575
     35723 4333 6023 3542 
     421 20 30 20 
Lymphatic invasion
     Absent78250.0925541-0.01480250.05845510.010
     Present25130.27220140.87126120.48615190.904
Lymph node metastasis
     Absent5825-0.02241350.02563200.18434420.052
     Present45130.54134200.77543170.82726280.554
Number of metastatic lymph nodes
     <5309-0.0522415-0.04131100.03119200.014
     >51540.5361050.6421270.708780.870
Lymph node pouch invasion
     Absent  -0.0484838-0.05371230.0234046-0.005
     Present  0.56823170.54135140.78220240.948
Distant metastasis
     Absent9135-0.0756551-0.0669236-0.1535264-0.085
     Present1230.3691040.4501410.046560.334
Tumor budding
     Absent5427-0.17446300.0696221-0.0073540-0.006
     Present49110.03629250.43344160.92725300.938
Necrosis
     Absent3270.1891913-0.1052712-0.00015160.089
     Focal39140.02325280.22942130.99427260.309
     Moderate259 2110 277 1511 
     Extensive78 104 105 317 

[i] Bold print indicates statistical significance. L, low; H, high.

Table III

Correlation between NLR and clinicopathological characteristics.

Table III

Correlation between NLR and clinicopathological characteristics.

 NLR
 Preoperative Postoperative 
ParametersLHR P-valueLHR P-value
Age, years
     <602315-0.2251223-0.114
     >6075310.00743510.196
Sex
     Female45110.1041931-0.046
     Male53460.21436430.602
Localization
     Right colon134-0.13298-0.009
     Transverse colon420.128220.922
     Left colon130 68 
     Sigmoid colon166 514 
     Rectum4927 2839 
Tumor growth
     Expanding8038-0.03049590.212
     Infiltrative1880.7206150.016
Tumor size, cm
     <2.51680.0049110.111
     2.5-5.065310.96136500.207
     >5.0177 1013 
TNM stage
     12811-0.06518180.124
     216120.43811150.161
     33921 1931 
     4152 710 
Adenocarcinoma type
     Mucinous component1811-0.0181058-0.006
     Non-mucinous80350.83145160.945
Grade of malignancy
     293430.1345172-0.015
     3530.108420.866
pT stage
     112-0.052210.037
     240150.53122280.676
     35528 2944 
     421 21 
Lymphatic invasion
     Absent76300.18141570.023
     Present22160.03014170.793
Lymph node metastasis
     Absent5628-0.03036420.200
     Present42180.71519320.023
Number of metastatic lymph nodes
     <53011-0.01412230.175
     >51270.861790.047
Lymph node pouch invasion
     Absent64310.00241470.232
     Present34150.98114270.008
Distant metastasis
     Absent8544-0.1044966-0.018
     Present1320.212690.832
Tumor budding
     Absent5727-0.06039410.152
     Present41190.47416330.084
Necrosis
     Absent2415-0.0041915-0.033
     Focal39160.96215340.703
     Moderate278 1419 
     Extensive87 76 

[i] Bold print indicates statistical significance. L, low; H, high.

Prognostic values of neutrophil count, lymphocyte count and NLR

The mean DFS of preNEU was 11.67 months in the low group and 9.97 months in the high group. Moreover, the mean DFS of postNEU was 9.57 in the low group and 11.79 in the high group. The postNEU in the low group was associated with a shorter DFS (P=0.055). The mean DFS of the preLYMPH group was similar in both groups and was estimated to be 11 months. The mean DFS of postLYMPH was 11.06 in the low group and 10.42 in the high group. The mean DFS of NLR was similar in both groups and was estimated to be ~11 months for preNLR and ~10 months for postNLR. DFS did not differ significantly among the preNEU, preLYMPH, postLYMPH, preNLR and postNLR groups (P=0.224, P=0.273, P=0.470, P=0.297 and P=0.554, respectively; Fig. 2A-F).

Discussion

The identification of chemotherapeutic targets for the treatment of advanced-stage CRC patients may increase the survival time of these subjects. However, the examination of the molecular predictive factors is costly and requires sophisticated laboratory equipment. There is a continuous search for low-cost, easy-to-obtain specific parameters that can detect early recurrence of cancer and monitor treatment efficacy (1). In the present study, the diagnostic and predictive value of specific parameters, such as neutrophil count, lymphocyte count and the combination of those parameters (NLR), pre- and postoperatively were determined from whole blood samples of patients with CRC. Neutrophils have been reported to have multiple functions in different types of tumors (16). Neutrophils are functionally classified into two subtypes: Tumor-suppressing (N1) and tumor-promoting (N2) neutrophils. They are located at the margin of the tumor site and are present at the early stages of cancer progression. They can also infiltrate into the center of the tumor in advanced lesions. A specific classification of circulating neutrophils has been characterized in the whole blood of patients with cancer; these can be divided based on their density into high-density neutrophils (HDNs) and low-density neutrophils (LDNs) (17). HDNs are functionally similar to N1 neutrophils, while LDNs resemble N2 neutrophils (18). Type N1 neutrophils have potent antitumor activity and release immunostimulatory cytokines, such as interleukin-12 and tumor necrosis factor-α (19). In contrast to these observations, N2 phenotype cells induce strong immunosuppressive and tumor-promoting activity, which produces pro-angiogenic chemokines and cytokines that are involved in tumor cell proliferation, invasion and vascularization (20). In the present study, the cut-off values of preNEU and postNEU were examined in whole blood samples of patients with CRC. The cut-off values exhibited moderate sensitivity and specificity, with ~77-79% of disease prevalence. Moreover, preNEU was correlated with tumor size and the presence of necrosis. In the first step, neutrophils are able to produce reactive oxygen species and reactive nitrogen species that cause DNA damage and genetic instability in cancer cells (21). Furthermore, neutrophils can secrete various mediators, such as hepatocyte growth factor, that lead to tumor growth and progression (22). Neutrophils are also involved in remodeling of the tumor extracellular matrix by the release of matrix metalloproteinase-9(23). The aforementioned properties of neutrophils were compared with tumor size and necrosis in previous studies and the data reported were consistent with our observations. However, the high neutrophil count noted in preoperative blood samples of patients with CRC exhibited a negative correlation with tumor budding. Tumor budding is defined as small clusters of cancer cells that are localized in the invasive margin of the primary tumor mass and they have important prognostic value. Ueno et al (24) demonstrated that tumor budding was observed in the margin of tumors with unfavorable fibrotic stroma. This cellular morphology was characterized by the presence of keloid-like collagen with random orientation of the fibrils and pervasive distribution of myofibroblasts. These histological characteristics of the tumor microenvironment likely determine the inhibition of the local and systemic immune response observed in patients with CRC. Moreover, high levels of neutrophil counts in whole blood samples were observed postoperatively in patients with non-mucinous CRC. The histological type of CRC was characterized by glandular cancer clusters in well-formed rich stroma, as opposed to the mucinous cancer type that exhibits spontaneous formation of cancer cells in mucin. The presence of the rich stroma may affect the immune response development and its effectiveness.

Lymphocytes are also involved in the organization of the immune response in malignant neoplasms (25). Our previous study indicated that patients with CRC who did not have intraepihethial tumor-infiltrating lymphocytes (TILs) in the center of the primary tumor mass exhibited shorter DFS (26). Moreover, the infiltration and distribution of TILs in tumor tissues of patients with CRC were associated with the invasion and progression of the disease. In the present study, the correlation between preLYMPH and distant metastasis was confirmed. Therefore, the NLR may be a factor reflecting the balance between the tumor-promoting property of neutrophils and the host antitumor immune response of lymphocytes. A total of 144 samples of whole blood were obtained prior to and following surgery. A ROC curve was used to estimate the cut-off values of NLR. The present analysis indicated that the cut-off of preNLR was 2.5 and that of postNLR was 3.3. These results are consistent with the observations of other studies that reported variations in these parameters between 2.5 and 5.0 (27-29). The present study demonstrated high sensitivity and specificity with positive disease prevalence for ~78% of the participants. Zhou et al (30) reported that the sensitivity and specificity of NLR for CRC were 66.9 and 77.6%, respectively; moreover, the NLR values were significantly higher compared with those in healthy volunteers. Pedrazzani et al (31) observed that the distribution of NLR was different between CRC patients and control subjects. Moreover, the NLR value was correlated with age, TNM stage, systemic metastasis and serum CEA levels. In the present study, preNLR and postNLR were correlated with age and various morphological characteristics of disease progression, such as lymphatic invasion, tumor growth, lymph node metastasis, number of invaded lymph nodes and invasion of the lymph node pouch. Furthermore, Chen et al (32) highlighted that high NLR was more prevalent in the elderly (>60 years) population and that it was associated with larger tumor size, advanced pT stage and positive N and M. Özgehan et al (33) demonstrated that NLR was higher in CRC patients with T3/4-N1/2-M1 stage compared with the corresponding value noted in patients with T1/1-N0-M0.

The present study analyzed the DFS of CRC patients in association with neutrophil count, lymphocyte count and NLR. The patients with low postNEU exhibited a higher tendency for shorter DFS. These results did not confirm the association of DFS with preLYMPH and postLYMPH in CRC patients. However, Iseki et al (34) confirmed that patients with higher lymphocyte count demonstrated a tendency for higher 5-year relapse-free survival rate. Moreover, patients with a high preLYMPH exhibited significantly longer overall survival. An association between DFS and NLR was not observed in blood samples between pre- and postoperative CRC patients. Jankova et al (35) demonstrated that preNLR could predict overall survival, although it was not specific to recurrence and cancer-specific survival. In contrast to these observations, Ying et al (36) indicated that elevated NLR levels were of prognostic value for recurrence-free, overall and cancer-specific survival in CRC patients who had undergone surgery. Balde et al (37) reported that the high preNLR group exhibited a higher recurrence rate compared with that of the low preNLR group. Li et al (38) demonstrated that a high preoperative NLR may be considered as a negative independent prognostic factor in non-metastatic rectal cancer. In addition, a previous study confirmed that a high preNLR was independently associated with poor prognosis of patients with CRC (39).

In conclusion, the findings of the present study indicated a significant correlation between specific blood indices in patients with CRC and disease progression markers, with only postNEU exhibiting a tendency of association disease prognosis. However, this preliminary evidence requires confirmation in studies with larger sample sizes.

Acknowledgements

Not applicable.

Funding

The author(s) received funding support from Medical University of Bialystok for the present study (grant no. N/ST/ZB/18/002/1194).

Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Authors' contributions

KJ collected data, performed analysis, wrote the manuscript, reviewed the literature, acquired the data and contributed to manuscript drafting; MK analysed and interpreted the pathological examination; WF, WK and LKK collected data; MG wrote the manuscript, reviewed the literature, acquired data and contributed to manuscript drafting. All authors reviewed and approved the final manuscript.

Ethics approval and consent to participate

The present study conformed to the principles outlined in the Declaration of Helsinki for human experimentation and the protocol was approved by the Bioethics Committee of the Medical University of Bialystok (approval no. R-I-002/353/2016). Written informed consent was obtained from all participants.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Maeda K, Shibutani M, Otani H, Nagahara H, Ikeya T, Iseki Y, Tanaka H, Muguruma K and Hirakawa K: Inflammation-based factors and prognosis in patients with colorectal cancer. World J Gastrointest Oncol. 7:111–117. 2015.PubMed/NCBI View Article : Google Scholar

2 

Hamilton S and Aaltonen L: Tumors of the colon and rectum. In: World Health Organization Classification of Tumors. Pathol Genet Tumors Dig Syst IARC Press Lyon pp103-104, 2000.

3 

Laird BJ, Kaasa S, McMillan DC, Fallon MT, Hjermstad MJ, Fayers P and Klepstad P: Prognostic factors in patients with advanced cancer: A comparison of clinicopathological factors and the development of an inflammation-based prognostic system. Clin Cancer Res. 19:5456–5464. 2013.PubMed/NCBI View Article : Google Scholar

4 

Lu H, Ouyang W and Huang C: Inflammation, a key event in cancer development. Mol Cancer Res. 4:221–233. 2006.PubMed/NCBI View Article : Google Scholar

5 

McMillan DC: The systemic inflammation-based Glasgow prognostic score: A decade of experience in patients with cancer. Cancer Treat Rev. 39:534–540. 2013.PubMed/NCBI View Article : Google Scholar

6 

Shibutani M, Maeda K, Nagahara H, Ohtani H, Sakurai K, Yamazoe S, Kimura K, Toyokawa T, Amano R, Tanaka H, et al: Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer. World J Gastroenterol. 21:9966–9973. 2015.PubMed/NCBI View Article : Google Scholar

7 

Rasic I, Rebic V, Rasic A, Aksamija G and Radovic S: The association of simultaneous increase in interleukin-6, C reactive protein, and matrix metalloproteinase-9 serum levels with increasing stages of colorectal cancer. J Oncol. 2018(2830503)2018.PubMed/NCBI View Article : Google Scholar

8 

Yamamoto M, Saito H, Uejima C, Tanio A, Takaya S, Sakamoto T, Honjo S, Maeta Y, Ashida K and Fujiwara Y: Prognostic value of the combination of pre- and postoperative C-reactive protein in colorectal cancer patients. Surg Today. 48:986–993. 2018.PubMed/NCBI View Article : Google Scholar

9 

Chua W, Charles KA, Baracos VE and Clarke SJ: Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer. 104:1288–1295. 2011.PubMed/NCBI View Article : Google Scholar

10 

Maeda K, Shibutani M, Otani H, Nagahara H, Sugano K, Ikeya T, Kubo N, Amano R, Kimura K, Muguruma K, et al: Low nutritional prognostic index correlates with poor survival in patients with stage IV colorectal cancer following palliative resection of the primary tumor. World J Surg. 38:1217–1222. 2014.PubMed/NCBI View Article : Google Scholar

11 

Zhou ZQ, Pang S, Yu XC, Xue Q, Jiang HY, Liang XJ and Liu L: Predictive values of postoperative and dynamic changes of inflammation indexes in survival of patients with resected colorectal cancer. Curr Med Sci. 38:798–808. 2018.PubMed/NCBI View Article : Google Scholar

12 

He WZ, Hu WM, Kong PF, Yang L, Yang YZ, Xie QK, Jiang C, Yin CX, Qiu HJ, Zhang B, et al: Systemic neutrophil lymphocyte ratio and mismatch repair status in colorectal cancer patients: Correlation and prognostic value. J Cancer. 9:3093–3100. 2018.PubMed/NCBI View Article : Google Scholar

13 

Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET and Carbone PP: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 5:649–655. 1982.PubMed/NCBI

14 

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC and Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 92:205–216. 2000.PubMed/NCBI View Article : Google Scholar

15 

Jakubowska K, Kisielewski W, Kańczuga-Koda L, Koda M and Famulski W: Diagnostic value of inflammatory cell infiltrates, tumor stroma percentage and disease-free survival in patients with colorectal cancer. Oncol Lett. 14:3869–3877. 2017.PubMed/NCBI View Article : Google Scholar

16 

Mayadas TN, Cullere X and Lowell CA: The multifaceted functions of neutrophils. Annu Rev Pathol Mech Dis. 9:181–218. 2014.PubMed/NCBI View Article : Google Scholar

17 

Sagiv JY, Voels S and Granot Z: Isolation and characterization of low- vs. High-density neutrophils in cancer. Methods Mol Biol. 1458:179–193. 2016.PubMed/NCBI View Article : Google Scholar

18 

Fridlender ZG and Albelda SM: Tumor-associated neutrophils: Friend or foe? Carcinogenesis. 33:949–955. 2012.PubMed/NCBI View Article : Google Scholar

19 

Coffelt SB, Wellenstein MD and De Visser KE: Neutrophils in cancer: Neutral no more. Nat Rev Cancer. 16:431–446. 2016.PubMed/NCBI View Article : Google Scholar

20 

Gregory AD and Houghton AM: Tumor-associated neutrophils: New targets for cancer therapy. Cancer Res. 71:2411–2416. 2011.PubMed/NCBI View Article : Google Scholar

21 

Powell DR and Huttenlocher A: Neutrophils in the tumor microenvironment. Trends Immunol. 37:41–52. 2016.PubMed/NCBI View Article : Google Scholar

22 

Brandau S, Moses K and Lang S: The kinship of neutrophils and granulocytic myeloid-derived suppressor cells in cancer: Cousins, siblings or twins? Semin Cancer Biol. 23:171–182. 2013.PubMed/NCBI View Article : Google Scholar

23 

Nozawa H, Chiu C and Hanahan D: Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci USA. 103:12493–12498. 2006.PubMed/NCBI View Article : Google Scholar

24 

Ueno H, Jones AM, Wilkinson KH, Jass JR and Talbot IC: Histological categorisation of fibrotic cancer stroma in advanced rectal cancer. Gut. 53:581–586. 2004.PubMed/NCBI View Article : Google Scholar

25 

Najafi M, Farhood B and Mortezaee K: Contribution of regulatory T cells to cancer: A review. J Cell Physiol. 234:7983–7993. 2019.PubMed/NCBI View Article : Google Scholar

26 

Jakubowska K, Kisielewski W, Kańczuga-Koda L, Koda M and Famulski W: Stromal and intraepithelial tumor-infiltrating lymphocytes in colorectal carcinoma. Oncol Lett. 14:6421–6432. 2017.PubMed/NCBI View Article : Google Scholar

27 

Nagasaki T, Akiyoshi T, Fujimoto Y, Konishi T, Nagayama S, Fukunaga Y and Ueno M: Prognostic impact of neutrophil-to-lymphocyte ratio in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy. Dig Surg. 32:496–503. 2015.PubMed/NCBI View Article : Google Scholar

28 

Palin RP, Devine AT, Hicks G and Burke D: Association of pretreatment neutrophil-lymphocyte ratio and outcome in emergency colorectal cancer care. Ann R Coll Surg Engl. 100:308–315. 2018.PubMed/NCBI View Article : Google Scholar

29 

Artaç M, Uysal M, Karaağaç M, Korkmaz L, Er Z, Güler T, Börüban MC and Bozcuk H: Prognostic impact of neutrophil/lymphocyte ratio, platelet count, CRP, and albumin levels in metastatic colorectal cancer patients treated with FOLFIRI-bevacizumab. J Gastrointest Cancer. 48:176–180. 2017.PubMed/NCBI View Article : Google Scholar

30 

Zhou WW, Chu YP and An GY: Significant difference of neutrophil-lymphocyte ratio between colorectal cancer, adenomatous polyp and healthy people. Eur Rev Med Pharmacol Sci. 21:5386–5391. 2017.PubMed/NCBI View Article : Google Scholar

31 

Pedrazzani C, Mantovani G, Fernandes E, Bagante F, Luca Salvagno G, Surci N, Campagnaro T, Ruzzenente A, Danese E, Lippi G and Guglielmi A: Assessment of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and platelet count as predictors of long-term outcome after R0 resection for colorectal cancer. Sci Rep. 7(1494)2017.PubMed/NCBI View Article : Google Scholar

32 

Chen L, Yan Y, Zhu L, Cong X, Li S, Song S, Song H and Xue Y: Systemic immune-inflammation index as a useful prognostic indicator predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy. Cancer Manag Res. 9:849–867. 2017.PubMed/NCBI View Article : Google Scholar

33 

Özgehan G, Kahramanca Ş, Kaya IO, Bilgen K, Bostanci H, Güzel H, Küçükpinar T and Kargici H: Neutrophil-lymphocyte ratio as a predictive factor for tumor staging in colorectal cancer. Turkish J Med Sci. 44:365–368. 2014.PubMed/NCBI View Article : Google Scholar

34 

Iseki Y, Shibutani M, Maeda K, Nagahara H, Tamura T, Ohira G, Yamazoe S, Kimura K, Toyokawa T, Amano R, et al: The impact of the preoperative peripheral lymphocyte count and lymphocyte percentage in patients with colorectal cancer. Surg Today. 47:743–754. 2017.PubMed/NCBI View Article : Google Scholar

35 

Jankova L, Dent OF, Chan C, Chapuis P and Clarke SJ: Preoperative neutrophil/lymphocyte ratio predicts overall survival but does not predict recurrence or cancer-specific survival after curative resection of node-positive colorectal cancer. BMC Cancer. 13(442)2013.PubMed/NCBI View Article : Google Scholar

36 

Ying HQ, Deng QW, He BS, Pan YQ, Wang F, Sun HL, Chen J, Liu X and Wang SK: The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol. 31(305)2014.PubMed/NCBI View Article : Google Scholar

37 

Balde AI, Fang S, He L, Cai Z, Han S, Wang W, Li Z and Kang L: Propensity score analysis of recurrence for neutrophil-to-lymphocyte ratio in colorectal cancer. J Surg Res. 219:244–252. 2017.PubMed/NCBI View Article : Google Scholar

38 

Li H, Song J, Cao M, Wang G, Li L, Zhang B, Li Y, Xu W and Zheng J: Preoperative neutrophil-to-lymphocyte ratio is a more valuable prognostic factor than platelet-to-lymphocyte ratio for nonmetastatic rectal cancer. Int Immunopharmacol. 40:327–331. 2016.PubMed/NCBI View Article : Google Scholar

39 

Ozdemir Y, Akin ML, Sucullu I, Balta AZ and Yuce E: Pretreatment neutrophil/lymphocyte ratio as a prognostic aid in colorectal cancer. Asian Pacific J Cancer Prev. 15:2647–2650. 2014.PubMed/NCBI View Article : Google Scholar

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November-2020
Volume 13 Issue 5

Print ISSN: 2049-9450
Online ISSN:2049-9469

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Spandidos Publications style
Jakubowska K, Koda M, Kisielewski W, Kańczuga‑Koda L, Grudzińska M and Famulski W: Pre‑ and postoperative neutrophil and lymphocyte count and neutrophil‑to‑lymphocyte ratio in patients with colorectal cancer. Mol Clin Oncol 13: 56, 2020
APA
Jakubowska, K., Koda, M., Kisielewski, W., Kańczuga‑Koda, L., Grudzińska, M., & Famulski, W. (2020). Pre‑ and postoperative neutrophil and lymphocyte count and neutrophil‑to‑lymphocyte ratio in patients with colorectal cancer. Molecular and Clinical Oncology, 13, 56. https://doi.org/10.3892/mco.2020.2126
MLA
Jakubowska, K., Koda, M., Kisielewski, W., Kańczuga‑Koda, L., Grudzińska, M., Famulski, W."Pre‑ and postoperative neutrophil and lymphocyte count and neutrophil‑to‑lymphocyte ratio in patients with colorectal cancer". Molecular and Clinical Oncology 13.5 (2020): 56.
Chicago
Jakubowska, K., Koda, M., Kisielewski, W., Kańczuga‑Koda, L., Grudzińska, M., Famulski, W."Pre‑ and postoperative neutrophil and lymphocyte count and neutrophil‑to‑lymphocyte ratio in patients with colorectal cancer". Molecular and Clinical Oncology 13, no. 5 (2020): 56. https://doi.org/10.3892/mco.2020.2126