Hindawi

BioMed Research International

Volume 2017, Article ID 7943467, 7 pages
https://doi.org/10.1155/2017/7943467

Review Article
Neutrophil-to-Lymphocyte Ratio Is a Potential Prognostic
Biomarker in Patients with Ovarian Cancer: A Meta-Analysis

Shubo Chen,1 Liu Zhang,2 Guangyue Yan,2 Sijin Cheng,2 Abdel Hamid Fathy,2
Nana Yan,3 and Yongzhao Zhao1,2
1
Department of Oncology, Wuxi Second Hospital, Nanjing Medical University, Wuxi, China
2
School of Medicine, Tongji University, Shanghai, China
3
Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China

Correspondence should be addressed to Yongzhao Zhao; [email protected]

Received 9 March 2017; Revised 22 May 2017; Accepted 8 June 2017; Published 26 July 2017

Academic Editor: Robert A. Vierkant

Copyright © 2017 Shubo Chen et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background and Aims. Plenty of studies were conducted to explore the prognostic significance of neutrophil-to-lymphocyte ratio
(NLR) in ovarian cancer with contradictory results. This study aims to summarize the prognostic significance of NLR in patients
with ovarian cancer. Methods. A literature search in PubMed, Cochrane Library, and Embase was conducted. The endpoints were
progression-free survival (PFS) and overall survival (OS). Results. Eleven studies involving a total of 2,892 patients were identified.
The results indicated that patients with high NLR had shorter PFS compared to patients with low NLR in ovarian cancer (HR =
1.55, 95% CI = 1.15–2.08, 𝑝 = 0.004, and 𝐼2 = 61%). Similarly, high NLR was related to shorter OS (HR = 1.51, 95% CI = 1.03–2.23,
𝑝 = 0.04, and 𝐼2 = 85%). Moreover, high NLR was significantly associated with shorter PFS when the NLR cut-off was less than 3.3
(𝑝 = 0.03) or when treatment is operation (𝑝 = 0.002). In addition, high NLR was distinctly related to worse OS in Asian people
(p = 0.04) or operation (p = 0.04). Conclusion. High NLR was associated with shorter PFS and shorter OS in ovarian cancer. NLR
is potentially a promising prognostic biomarker in patients with ovarian cancer.

1. Introduction As is well-known, inflammation plays an important role

in tumor growth, invasion, and metastasis. And the prognos-
Ovarian cancer is one of the most common gynecological tic value of systemic inflammatory response (SIR) markers
diseases in oncology, and there were 238,700 estimated new has been well studied, which included platelet to lympho-
cases and 151,900 related deaths in 2012 all over the world [1]. cyte ratio (PLR), C-reactive protein, and MicroRNAs [6,
Lots of patients are at advanced stage at the first diagnosis, 7]. In recent studies, neutrophil-to-lymphocyte ratio (NLR)
which accounts for the high mortality. The mainstream ther- was identified as a crucial prognostic biomarker in various
apy for early ovarian cancer is still the operation with or with- tumors [8–13]. Meanwhile, plenty of studies were carried
out adjuvant chemotherapy, and chemotherapy is the most out to explore the prognostic significance of neutrophil-to-
common therapy for the advanced ovarian cancer. However, lymphocyte ratio in ovarian cancer; however, the results were
the outcome of the primary therapy remains poor, around contradictory [14–24]. The study conducted by Thavaramara
50% of the patients will have a relapse occurring within 16 et al. 2011 presented that there were no obvious relationship
months, and the 5-year overall survival rate is still below between the NLR and PFS (≤2.60 versus >2.60) (HR = 0.70,
50% [2]. Therefore, more attention is paid to the promising 95% CI = 0.35–1.40, and p = 0.344) or OS (≤2.60 versus
prognostic factors to improve the prognosis of ovarian >2.60) (HR = 0.70, 95% CI = 0.31–1.60, and p = 0.399) [16],
cancer, and the promising prognostic factors mainly include and similar results were detected in the study conducted by
age, stage, and tumor biomarkers [3–5]. Asher et al. in terms of OS (≤4.0 versus >4.0) (HR = 0.87,
2 BioMed Research International

95% CI = 0.52–1.44, and p = 0.575) [15]. Besides, Miao et 305 records identified through
al. covered that high NLR was associated with worse PFS database searching
(≤3.02 versus >3.02) (HR = 1.73, 95% CI = 1.23–2.45, and p
= 0.002) or OS (≤3.02 versus >3.02) (HR = 1.62, 95% CI =
1.14–2.29, and p = 0.007) [22]; however, Zhang et al. reported 173 records excluded
187 records after duplicates by scanning the
that low NLR was an unfavourable factor in terms of PFS were removed
abstracts or titles
(≤3.40 versus >3.40) (HR = 0.50, 95% CI = 0.36–0.68, and
𝑝 < 0.001) and OS (≤3.40 versus >3.40) (HR = 0.46, 95%
CI = 0.33–0.65, and 𝑝 < 0.001) [19]. Hence, controversy 14 full-text articles
3 excluded for not
reporting the PFS or
focusing on the relationship between the NLR and prognosis assessed for eligibility
OS
of ovarian cancer indeed exists. The aim of this meta-analysis
was to explore the prognostic significance of NLR in ovarian
cancer. 11 studies included in
qualitative synthesis
2. Methods
2.1. Literature Search Strategy. A complete systematic liter- 11 studies included in
ature search method was implemented using PubMed, the quantitative synthesis
Cochrane Library, and Embase up to December 25, 2016. The (meta-analysis)
search strategy was “((Ovarian cancer) OR (Ovarian Neo-
plasm) OR (Ovary Neoplasm) OR (Ovary Cancer) OR (Can- Figure 1: Flow diagram of study selection process.
cer of Ovary) OR (Cancer of the Ovary)) AND ((neutrophil-
lymphocyte ratio) OR (neutrophil-to-lymphocyte ratio) OR
(neutrophil AND lymphocyte) OR NLR)”. The reference lists
random-effect model was used; otherwise, the fixed-effects
were also checked. The irrelevant articles were excluded by
model was used. Besides, Egger’s test and Begg’s test were
scanning the titles or abstracts. The remaining articles were
both conducted to evaluate publication bias by Stata 12.0. The
then reviewed comprehensively by reading the full text.
sensitivity analysis was conducted by Stata 12.0 to access the
robustness of the results. 𝑝 < 0.05 was considered statistically
2.2. Inclusion Criteria. The included study should meet all significant.
the criteria as follows: (1) retrospective or prospective studies;
(2) focusing on the role of NLR on the prognosis in ovarian
cancer; (3) enough data to get the hazard ratio (HR) for 3. Results
progression-free survival (PFS) or overall survival (OS), 3.1. Literature Search. As shown in Figure 1, a total of
along with their 95% confidence intervals (CIs) or p values; 305 papers retrieved, 187 papers remained after duplicates
(4) published in English. removed, and 173 papers were excluded by scanning the titles
or abstracts. For the 14 potentially related studies remaining,
2.3. Data Extraction and Quality Assessment. All the manu- 3 were excluded for insufficient datum to assess the prognosis
scripts were independently reviewed by two investigators. outcomes. At last, 11 studies involving 2,892 patients were
The following data was abstracted: family name of the first eligible for this meta-analysis [14–24].
author, year of publication, country of the study, ethnicity
of the study, sample size, cut-off value of NLR, therapy, 3.2. Characteristics of Included Studies. As listed in Table 1,
and survival analysis. The HRs of PFS or OS obtained the eleven included studies contained 2,892 patients. Four
directly or indirectly from published articles were integrated studies paid attention to the role of NLR on the prognosis
in the meta-analysis according to the study conducted by of patients receiving the chemotherapy [18, 19, 22, 23] and
Tierney et al. [25]. The HR assessed with multivariate analysis the others focused on the operation [14–17, 20, 21, 24].
was abstracted when the multivariate analysis and univari- The sample size varied from 30 patients to 875 patients.
ate analysis were both applied. Newcastle-Ottawa Quality Besides, nine studies focused on the Asian [14, 16, 18–24]
Assessment Scale (NOS) was used to assess the quality of and two studies focused on the Caucasian [15, 17]. All the
each study. Any discrepancies were discussed with the third included studies reported the OS [14–24]; however, only
investigator. seven studies covered the PFS [16, 18–22, 24]. In addition,
nine studies reported the value of cut-off [14–16, 19–24]. As
2.4. Statistical Analysis. All the meta-analyses were carried shown in Supplementary Table 1 (Supplementary Material,
out by Review Manager Version 5.3 software. The prognosis available online at https://doi.org/10.1155/2017/7943467), the
outcomes were explored using the HR, along with the main adjusted factors in the OS included age, stage, grade,
corresponding 95% CI. The prognosis outcomes contained PLR, CA125, and residual disease.
the PFS or OS. The heterogeneity was assessed by Cochran’s 𝑄
test and Higgins 𝐼2 across studies. The heterogeneity should 3.3. Meta-Analysis of PFS. Eight studies reported the PFS;
be considered when 𝑝 < 0.05 and/or 𝐼2 > 50%, and the however, the study conducted by Cho et al. was excluded for
BioMed Research International 3

Hazard ratio Hazard ratio

Study or subgroup log[hazard ratio] SE Weight
IV, random, 95% CI IV, random, 95% CI
Zhang et al., 2015 −0.6992 0.1575 16.4% 0.50 [0.36, 0.68]
Thavaramara et al., 2011 −0.3567 0.3537 12.3% 0.70 [0.35, 1.40]
Zheng et al., 2016 0.2231 0.088 17.4% 1.25 [1.05, 1.49]
Miao et al., 2016 0.5499 0.177 16.0% 1.73 [1.23, 2.45]
Kim et al., 2016 0.7129 0.3587 12.2% 2.04 [1.01, 4.12]
Wang et al., 2016 0.7885 0.3872 11.5% 2.20 [1.03, 4.70]
Wang et al., 2015 0.8162 0.2664 14.2% 2.26 [1.34, 3.81]

Total (95% CI) 100.0% 1.30 [0.84, 2.00]

Heterogeneity: 2 = 0.27; 2 = 48.34, df = 6 (p < 0.00001); I2 = 88%
0.01 0.1 1 10 100
Test for overall effect: Z = 1.19 (p = 0.24) Favours [high NLR] Favours [low NLR]

Figure 2: Meta-analysis of progression-free survival.

Table 1: Characteristics of the included studies.

Sample Progression-free
Study Country Ethnicity Cut-off Therapy Overall survival NOS†
size survival
Cho et al. 2009 [14] South Korea Asian 192 2.6 Operation NR∫ 8.42 [1.09, 65.04] 7
Thavaramara et al. 2011
Thailand Asian 129 2.6 Operation 0.70 [0.35, 1.40] 0.70 [0.31, 1.60] 6
[16]
United
Asher et al. 2011 [15] Caucasian 235 4.0 Operation NR∫ 0.87 [0.52, 1.44] 6
Kingdom
United
Williams et al. 2014 [17] Caucasian 519 NR∫ Operation NR∫ 1.43 [1.13, 1.81] 6
States
Wang et al. 2015 [18] China Asian 126 NR∫ Chemotherapy 2.26 [1.34, 3.81] 3.25 [1.74, 6.08] 8
Zhang et al. 2015 [19] China Asian 190 3.4 Chemotherapy 0.50 [0.36, 0.68] 0.46 [0.33, 0.65] 6
Miao et al. 2016 [22] China Asian 344 3.02 Chemotherapy 1.73 [1.23, 2.45] 1.62 [1.14, 2.29] 6
Kim et al. 2016 [21] South Korea Asian 109 2.8 Operation 2.04 [1.01, 4.12] 3.45 [1.47, 8.10] 6
Nakamura et al. 2016 [23] Japan Asian 30 3.91 Chemotherapy NR∫ 14.13 [1.21, 165.36] 6
Wang et al. 2016 [24] China Asian 143 3.43 Operation 2.20 [1.03, 4.70] 3.37 [1.39, 8.15] 6
Feng et al. 2016 [20] China Asian 875 3.24 Operation 1.25 [1.05, 1.49] 1.19 [0.94, 1.50] 8
∫
NR, not reported; † NOS, Newcastle-Ottawa Scale.

data deficiencies [14]. As shown in Figure 2, no significant analysis stratified by NLR cut-off value showed that the
correlation was observed between the high NLR and PFS high NLR was a risk factor when cut-off value <3.3 (HR
(HR = 1.30, 95% CI = 0.84–2.00, and p = 0.24), with large = 1.39, 95% CI = 1.03–1.89, and p = 0.03; I 2 = 53%), but
heterogeneity (I 2 = 88%, 𝑝 < 0.0001). Based on the sensitivity no significant correlation between the NLR and PFS was
analysis conducted by Stata 12.0, Zhang et al. was finally observed when cut-off value ≥3.3. With respect to the therapy,
excluded (Supplementary Figure 1). Therefore, six studies the pooled effect estimates indicated a significant correlation
involving 1,726 patients were finally included in the meta- between high pretreatment NLR and operation (HR = 1.29,
analysis of PFS and the HR of each study was assessed by 95% CI = 1.10–1.51, and p = 0.002; I 2 = 47%), but no
multivariate analysis. As shown in Figure 3, in consideration statistical significance between high pretreatment NLR and
of the large heterogeneity (I 2 = 61%, p = 0.03), the random- chemotherapy was detected.
effect model was employed. The results indicated that high
NLR appeared to be a stronger predictor of risk when 3.4. Meta-Analysis of OS. Eleven studies covered the OS and
compared to low NLR (HR = 1.55, 95% CI = 1.15–2.08, and were included into the meta-analysis of OS. As shown in
p = 0.004). Besides, sensitivity analysis demonstrated that Figure 4, in view of the large heterogeneity, the random-effect
the combined HRs of PFS did not significantly alter when model was applied (I 2 = 85%, 𝑝 < 0.0001). The meta-analysis
excluding any study by turn (Supplementary Figure 2). And revealed that patients with high NLR might have shorter OS
no publication bias among six included studies was detected compared to the patients with low NLR (HR = 1.51, 95% CI
(Begg test, p = 1.000; Egger test, p = 0.361). = 1.03–2.23, and p = 0.04). Regarding the subgroup analysis
Seven studies were enrolled into the subgroup analysis of of multivariate analyses, the meta-analysis containing nine
PFS. As listed in Table 2, the subgroup analyses were carried studies indicated significant superiority of a low NLR in
out to investigate the sources of heterogeneity. Subgroup ovarian cancer (HR = 1.56, 95% CI = 1.15–2.13, and p = 0.005),
4 BioMed Research International

Hazard ratio Hazard ratio

Study or subgroup log[hazard ratio] SE Weight
IV, random, 95% CI IV, random, 95% CI
Thavaramara et al., 2011 −0.3567 0.3537 11.6% 0.70 [0.35, 1.40]
Zheng et al., 2016 0.2231 0.088 28.6% 1.25 [1.05, 1.49]
Miao et al., 2016 0.5499 0.177 22.1% 1.73 [1.23, 2.45]
Kim et al., 2016 0.7129 0.3587 11.4% 2.04 [1.01, 4.12]
Wang et al., 2016 0.7885 0.3872 10.3% 2.20 [1.03, 4.70]
Wang et al., 2015 0.8162 0.2664 16.0% 2.26 [1.34, 3.81]

Total (95% CI) 100.0% 1.55 [1.15, 2.08]

Heterogeneity: 2 = 0.07; 2 = 12.66, df = 5 (p = 0.03); I2 = 61%
0.01 0.1 1 10 100
Test for overall effect: Z = 2.89 (p = 0.004) Favours [high NLR] Favours [low NLR]

Figure 3: Meta-analysis of progression-free survival when Zhang et al. was excluded.

Hazard ratio Hazard ratio

Study or subgroup log[hazard ratio] SE Weight
IV, random, 95% CI IV, random, 95% CI
Multivariate analyses
Asher et al., 2011 −0.145 0.2587 10.9% 0.87 [0.52, 1.44]
Cho et al., 2009 2.1306 1.0431 2.8% 8.42 [1.09, 65.04]
Miao et al., 2016 0.48 0.1789 12.1% 1.62 [1.14, 2.29]
Nakamura et al., 2016 2.6482 1.2551 2.1% 14.13 [1.21, 165.36]
Thavaramara et al., 2011 −0.3567 0.4218 8.3% 0.70 [0.31, 1.60]
Wang et al., 2015 1.1799 0.3191 9.9% 3.25 [1.74, 6.08]
Wang et al., 2016 1.2149 0.4506 7.9% 3.37[1.39, 8.15]
Williams et al., 2014 0.3577 0.1201 12.8% 1.43 [1.13, 1.81]
Zheng et al., 2016 0.1731 0.1199 12.8% 1.19 [0.94, 1.50]
Subtotal (95% CI) 79.7% 1.56 [1.15, 2.13]
Heterogeneity: 2 = 0.12; 2 = 25.83, df = 8 (p = 0.001); I2 = 69%
Test for overall effect: Z = 2.82 (p = 0.005)

Univariate analysis
Kim et al., 2016 1.2384 0.4353 8.1% 3.45 [1.47, 8.10]
Zhang et al., 2015 −0.7757 0.1746 12.2% 0.46 [0.33, 0.65]
Subtotal (95% CI) 20.3% 1.21 [0.17, 8.71]
Heterogeneity: 2 = 1.92; 2 = 18.44, df = 1 (p < 0.0001); I2 = 95%
Test for overall effect: Z = 0.19 (p = 0.85)

Total (95% CI) 100.0% 1.51 [1.03, 2.23]

Heterogeneity: 2 = 0.29; 2 = 66.39, df = 10 (p < 0.00001); I2 = 85%
Test for overall effect: Z = 2.11 (p = 0.04) 0.01 0.1 1 10 100
Favours [high NLR] Favours [low NLR]

Figure 4: Meta-analysis of overall survival.

however, with clear heterogeneity (I 2 = 69%, p = 0.0001). Asian population, with heterogeneity (HR = 1.76, 95% CI =
Meanwhile, the sensitivity analysis demonstrated that the 1.03–3.00, and p = 0.04; I 2 = 87%), but no evident correlation
combined HRs of PFS did not clearly alter when excluding between the NLR and OS was found in Caucasian population.
any study by turn (Supplementary Figure 3). There was no In respect to the therapy, apparent correlation between the
publication bias among nine included studies (Begg test, p = preoperation NLR and OS was found, and high NLR might
0.175; Egger test, p = 0.160). Nevertheless, in the subgroup predict worse OS when compared to the low NLR (HR = 1.45,
analysis of univariate analyses, no obvious difference was 95% CI = 1.02–2.04, and p = 0.04; I 2 = 68%); nevertheless, no
observed between the patients with high NLR and patients significant relationship between the NLR and chemotherapy
with low NLR (HR = 1.21, 95% CI = 0.17–8.17, and p = 0.85; I 2 was observed.
= 95%).
As listed in Table 2, the subgroup analysis was employed 4. Discussion
in terms of OS. No apparent correlation was detected between
the NLR and OS regardless of the NLR cut-off value <3.3 Increasing evidence has indicated that inflammatory
or ≥3.3. Regarding the ethnicity, the results presented that response might be involved in the occurrence and growth
the patients with high NLR faced a greater risk of death in of various tumors [26–31]. And inflammation-related
BioMed Research International 5

Table 2: Summary of the subgroup analysis results of NLR on PFS and OS.

Survival analysis Included studies Patients HR 95% CI p I2 p for heterogeneity

PFS
Cut-off value
<3.3 4 1,457 1.39 [1.03, 1.89] 0.03‡ 53% 0.1
≥3.3 2 333 1.00 [0.23, 4.30] 1 92% 0.0004
Ethnicity
Asian 7 1,916 1.31 [0.85, 2.03] 0.22 87% <0.00001
Therapy
Chemotherapy 3 660 1.23 [0.47, 3.24] 0.67 95% <0.00001
Operation 4 1,256 1.29 [1.10, 1.51] 0.002‡ 47% 0.13
OS
Cut-off value
<3.3 5 1,694 1.53 [0.99, 2.39] 0.06 67% 0.02
≥3.3 4 598 1.37 [0.51, 3.64] 0.53 88% <0.0001
Ethnicity
Asian 9 2,138 1.76 [1.03, 3.00] 0.04‡ 87% <0.00001
Caucasian 2 754 1.17 [0.72, 1.90] 0.52 68% 0.08
Therapy
Chemotherapy 4 690 1.73 [0.60, 4.94] 0.31 93% <0.00001
Operation 7 2,202 1.45 [1.02, 2.04] 0.04‡ 68% 0.005
PFS, progression-free survival; OS, overall survival; ‡
푝 < 0.05, the difference was significant.

neutrophils and lymphocytes are also crucial to tumor In our meta-analysis, the results showed that high NLR
growth, invasion, and metastasis. NLR, a promising was significantly associated with worse PFS when compared
prognostic factor, has been fully researched in many kinds of with the low NLR. And study conducted by Badora-Rybicka
tumors [32–34]. However, the association between high NLR et al. also covered that pretreatment high NLR was a neg-
and various cancers remains complicated. The mechanism ative prognostic factor for ovarian cancer in terms of PFS
underlying the association between high NLR and poor [31]. However, Zhang et al. reported that high NLR was a
outcomes in various cancers remains unclear [6, 35, 36]. favourable prognostic factor for ovarian cancer in terms of
Some tumor-promoting cytokines might play a critical role PFS (≤3.4 versus >3.4, HR = 2.012, 95% CI = 1.476–2.741, and
in the development of tumorigenesis, such as nuclear factor 𝑝 < 0.001) [19]. It is important to be noted that the study con-
kB (NF-kB) and transducer and activator of transcription ducted by Zhang et al. only involved 190 patients and the HR
3 (STAT3) [37]. These tumor-promoting cytokines could of PFS was assessed by univariate analysis, which might heav-
change the expression level of cancer-related genes and ily reduce the reliability [19]. Besides, high NLR was related to
promote normal cells to transform into cancer cells and then worse PFS when the value of cut-off <3.3 or before operation.
help the invasion and metastasis of tumor cells. In addition, Regarding the OS, high NLR was significantly associated
with the assistance of cytokines, cancer cells might facilitate with worse OS, especially when the eligible studies were
recruitment of tumor-associated neutrophils, which further all assessed with multivariate analysis. Besides, the obvious
help the tumor metastasis. Instead, lymphocytes are faithful correlation between the high NLR and poor OS was only
anticancer defenders, and high lymphocyte counts have been observed in Asian, not in Caucasian, population. More
proved as a favourable factor in terms of survival in a good studies in Caucasian people should be carried out because
way in many human cancers [38, 39]. The abovementioned only two studies were enrolled into the subgroup analysis of
mechanism might indicate that high NLR is an unfavourable Caucasian people. And Badora-Rybicka et al. also reported
factor in most cancers [28–31]. that high NLR was related to shorter OS compared with low
NLR is easily obtained from a routine blood test without NLR before the operation [31]. Nevertheless, Zhang et al.
additional cost. And the changes of NLR are breezily detected reported that high NLR was apparently associated with longer
in the process of treatment of ovarian cancers. Therefore, OS for ovarian cancer (≤3.4 versus >3.4, HR = 2.172, 95%
NLR is a promising predictor in the individual treatment and CI = 1.545–3.054, and 𝑝 < 0.001), which was assessed by
more and more attention was paid to detecting the role of multivariate analysis [19]. Besides, the heterogeneity of the
NLR on the prognosis of the ovarian cancer [14–24]. Several meta-analysis of PFS obviously increased when Zhang et al.
retrospective studies were carried out to determine the effect study was included into the analysis, which might heavily
of NLR on the prognosis of the ovarian cancer, but with reduce the reliability. Therefore, Zhang et al. study was finally
contradictory results [16, 18, 19, 21, 24]. excluded from the current meta-analysis of PFS. In addition,
6 BioMed Research International

the obvious correlation between the high NLR and shorter OS Tumor Bank Ovarian Cancer (TOC),” Cytokine, vol. 85, pp. 157–
was observed for patients before operation. 164, 2016.
The highlighted strengths of our meta-analysis are as [5] P. P. Santoiemma, C. Reyes, L.-P. Wang et al., “Systematic
follows. Firstly, at present, this study was the first meta- evaluation of multiple immune markers reveals prognostic
analysis to explore the prognostic significance of neutrophil- factors in ovarian cancer,” Gynecologic Oncology, vol. 143, no.
to-lymphocyte ratio in ovarian cancer. Secondly, eleven stud- 1, pp. 120–127, 2016.
ies with a relatively large population were finally included; [6] D. Hanahan and R. A. Weinberg, “Hallmarks of cancer: the next
thus, the results were convincing. Thirdly, the subgroup generation,” Cell, vol. 144, no. 5, pp. 646–674, 2011.
analyses were carried out based on the NLR cut-off, therapy, [7] L. Guo, Y. Zhang, L. Zhang, F. Huang, J. Li, and S. Wang,
and ethnicity; therefore, the analysis was comprehensive. “MicroRNAs, TGF-𝛽 signaling, and the inflammatory microen-
However, some limitations of our study should be considered. vironment in cancer,” Tumor Biology, vol. 37, no. 1, pp. 115–125,
Firstly, only one study reported the postoperative NLR on the 2016.
prognosis of ovarian cancer and was not included into the [8] S. Albayrak, K. Zengin, S. Tanik et al., “Can the neutrophil-to-
study; therefore, the study only focused on the pretreatment lymphocyte ratio be used to predict recurrence and progression
NLR and on the prognosis of ovarian cancer. Secondly, plenty of non-muscle-invasive bladder cancer?” Kaohsiung Journal of
Medical Sciences, vol. 32, no. 6, pp. 327–333, 2016.
of analyses had a significant heterogeneity, which might
reduce the accuracy of the results. Thirdly, the individual data [9] O. Buisan, A. Orsola, J. Areal et al., “Low pretreatment
neutrophil-to-lymphocyte ratio predicts for good outcomes in
was unavailable, like drug dose, curative time, and so on.
patients receiving neoadjuvant chemotherapy before radical
Fourthly, some included studies reported limited information cystectomy for muscle invasive bladder cancer,” Clinical Geni-
of the therapy; therefore, possible misclassification of therapy tourinary Cancer, vol. 15, no. 1, pp. 145–151, 2016.
might exist in the current meta-analysis.
[10] W. Gong, S. Yang, X. Yang, and F. Guo, “Blood preoperative
In summary, our study demonstrated that high NLR neutrophil-to-lymphocyte ratio is correlated with TNM stage in
predicted worse PFS and OS in patients with ovarian cancer, patients with papillary thyroid cancer,” Clinics, vol. 71, no. 6, pp.
especially significantly associated with shorter PFS when cut- 311–314, 2016.
off <3.3 or preoperation, and obviously related to worse OS [11] J. Kasuga, T. Kawahara, D. Takamoto et al., “Increased
in Asian people or preoperation. However, the conclusion neutrophil-to-lymphocyte ratio is associated with disease-
should be used with caution for the limitations listed above specific mortality in patients with penile cancer,” BMC Cancer,
and more multicenter prospective cohorts should be carried vol. 16, no. 1, article 396, 2016.
out to explore the prognostic significance of neutrophil-to- [12] I. Nikolić, S. Kukulj, M. Samaržija et al., “Neutrophil-to-
lymphocyte ratio in ovarian cancer. lymphocyte and platelet-to-lymphocyte ratio help identify
patients with lung cancer, but do not differentiate between lung
cancer subtypes,” Croatian Medical Journal, vol. 57, no. 3, pp.
Conflicts of Interest 287–292, 2016.
The authors have declared no conflicts of interest. [13] X. Sun, X. Liu, J. Liu et al., “Preoperative neutrophil-to-
lymphocyte ratio plus platelet-to-lymphocyte ratio in predict-
ing survival for patients with stage I–II gastric cancer,” Chinese
Authors’ Contributions Journal of Cancer, vol. 35, no. 1, 2016.
[14] H. Cho, H. W. Hur, S. W. Kim et al., “Pre-treatment neutrophil
Yongzhao Zhao and Shubo Chen were responsible for study to lymphocyte ratio is elevated in epithelial ovarian cancer
concepts and design; Yongzhao Zhao conducted litera- and predicts survival after treatment,” Cancer Immunology,
ture search; Yongzhao Zhao, Liu Zhang, and Shubo Chen Immunotherapy, vol. 58, no. 1, pp. 15–23, 2009.
extracted data; Guangyue Yan, Nana Yan, Sijin Cheng, Abdel [15] V. Asher, J. Lee, A. Innamaa, and A. Bali, “Preoperative platelet
Hamid Fathy, and Yongzhao Zhao prepared and revised the lymphocyte ratio as an independent prognostic marker in
manuscript. All authors have participated sufficiently in the ovarian cancer,” Clinical and Translational Oncology, vol. 13, no.
study and approved the final version. 7, pp. 499–503, 2011.
[16] T. Thavaramara, C. Phaloprakarn, S. Tangjitgamol, and S.
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