Journal of Cancer 2018, Vol.

9 1877

Ivyspring
International Publisher
Journal of Cancer
2018; 9(10): 1877-1884. doi: 10.7150/jca.23320
Research Paper

Prognostic value of C-reactive protein/albumin ratio in

predicting overall survival of Chinese cervical cancer
patients overall survival: comparison among various
inflammation based factors
Xia He*, Jian-Pei Li*, Xiao-Hua Liu, Jing-Ping Zhang, Qiu-Yao Zeng, Hao Chen and Shu-Lin Chen 
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou
510060, China.

*These authors contributed equally to this work.

 Corresponding authors: [email protected] (H.C.); Tel./Fax: +86-20-8734-3268 and [email protected] (S.-L.C.); Tel./Fax: +86-20-8734-3438

© Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license
(https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

Received: 2017.10.14; Accepted: 2018.01.24; Published: 2018.04.27

Abstract
Background: Many studies have shown the prognostic value of inflammation based factors in different
cancers. This work aimed to explore the prognostic value of pretreatment C-reactive protein/albumin
(CRP/Alb) ratio in patients with cervical cancer, and compared to other inflammatory prognostic factors,
such as neutrophil/lymphocyte ratio(NLR), Glasgow prognostic score (mGPS), prognostic index (PI),
platelet/lymphocyte ratio (PLR), prognostic nutritional index (PNI), clinicopathological parameter and
squamous cell carcinoma antigen (SCC-Ag).
Methods: This study was a retrospective analysis of the data related to 229 patients with newly
diagnosed cervical cancer. The potential prognostic factors were evaluated by univariate and multivariate
survival analysis. The correlation between CRP/Alb ratio and other prognostic factors were analyzed by
Chi-Square or Fisher’s exact test.
Results: Multivariate analyses showed that CRP/Alb ratio was an independent predictor of overall
survival (OS) in cervical squamous cell carcinoma (SCC) (HR, hazard ratio = 2.529; p = 0.045), but not in
all cases of cervical cancer. However, NLR was a prognostic factor in the whole cervical cancer (HR =
2.47; p = 0.020) as well as in SCC subgroup (HR = 2.28; p = 0.038). Spearman's rank correlation analysis
revealed that NLR showed a positive correlation with CRP/Alb ratio (p < 0.001). The combined index of
NLR and CRP/Alb ratio could enhance the prognostic value compared to NLR or CRP/Alb ratio alone.
Moreover, a high CRP/Alb ratio > 0.022 was associated with older patients (p < 0.001) and more
advanced International Federation of Gynecology and Obstetrics (FIGO) stages (p < 0.001). In addition,
NLR and CRP/Alb ratio were associated with SCC-Ag concentration in SCC. Furthermore, CRP/Alb
ratio was a superior prognosis factor than mGPS, PI, PLR and PNI in SCC. Moreover, positive correlation
was present among SCC-Ag, NLR and CRP/Alb ratio.
Conclusions: CRP/Alb ratio might be considered as a novel prognosis factor and combined with NLR
could improve the accuracy of OS prediction in patients with cervical cancer as well as its most common
histological SCC subtypes.
Key words: Cervical cancer, inflammation based factors, C-reactive protein/albumin ratio,
neutrophil/lymphocyte ratio(NLR), overall survival

Introduction
Cervical cancer is the second most commonly cancer death among females in less developed
diagnosed cancer and the third leading cause of countries [1]. Nearly one-third of patients with

http://www.jcancer.org
Journal of Cancer 2018, Vol. 9 1878

cervical cancer die due to disease recurrence or carcinoma, small cell lung carcinoma and esophageal
progression [2]. In order to take a precise individual squamous cell carcinoma. However, it is unknown
treatment in patients with cervical cancer, the whether pretreatment CRP/Alb ratio is a prognostic
discovery of suitable markers for a correct prognosis marker in patients with cervical cancer, and whether
evaluation is urgently needed. its prognostic value is or not superior to other inflam-
Currently, clinical stages and several matory prognostic factors. Therefore, the aim of our
pathological features, including invasion depth, study was to investigate the prognostic value of CRP/
lymph node (LN) status and tumor size are often used Alb ratio in patients with cervical cancer, and compa-
to predict recurrence in cervical cancer [3-4]. red it to other prognostic factors (CRP, PNI, PI and
However, some researches showed that clinical stages mGPS), cellular parameters (NLR, PLR) and SCC-Ag.
were not accurate enough [5-6] and the pathological
risk factors for prognosis cannot be used in patients Materials and Methods
without surgery. Furthermore, few markers can
Ethics statement
accurately predict the prognosis and their validity is
still controversial. All patients provided written informed consent
Squamous cell carcinoma (SCC) accounting for to participate to this survey. The study was approved
about 85% is the most common histological subtypes by the Ethics Committee of Sun Yat-Sen University
of cervical carcinoma [7]. Squamous cell carcinoma Cancer Center.
antigen (SCC-Ag) is the most commonly used Study population
biomarker to screen SCC of the cervix; it is related to
Patients with first diagnosed cervical cancer who
tumor stage, tumor size, the amount of residual tumor
were treated at Sun Yat-sen University Cancer Center
after treatment and recurrence [8]. SCC-Ag in high
from September 2007 to March 2009 were retro-
levels can precede the clinical diagnosis of recurrent
spectively enrolled in our study. All the data were
disease in 46%-92% of the cases; however, its
collected before treatment. The exclusion criteria were
effectiveness in prognosis prediction is still under
the following: 1. the patients without pathological
debated [9-10].
diagnosis or with previous or concomitant malignan-
The systemic inflammatory response is
cies; 2. incomplete records in the database of medical
associated with carcinogenesis, tumor progression
information; 3. patients lost during follow-up, or
and metastasis (Balkwill and Mantovani 2001;
patients who died because of non-cancer causes; 4. in
Candido and Hagemann 2013; Diakos et al. 2014;
order to eliminate the influences of non-cancer
Werb 2002). There are substantial evidences that the
diseases on inflammation-based prognostic factors,
host systemic inflammatory response is an important
we excluded patients with rheumatoid diseases and
independent outcomes predictor in cancer patients
acute infection. Finally, 229 patients were enrolled in
and that pretreatment measures of the systemic
our study. The authenticity of this article has been
inflammatory parameters can be used to
validated by uploading the key raw data onto the
independently predict cancer survival. C-reactive
Research Data Deposit public platform (www.
protein albumin (CRP) test is great significance in the
researchdata.org.cn), with the approval RDD number
early diagnosis, differential diagnosis and observation
as RDDA2018000550.
of curative effects. Suyang Guo et al. aslo confirmed
the role of CRP in the early diagnosis of cervical Clinicopathological features
cancer recurrence [11]. Several nutrition-based and Baseline participants’ characteristics of
(or) inflammatory factors have been applied to predict participants were gathered from medical records
the survival time in many cancers, such as including age, FIGO stages, histological typing,
neutrophil/lymphocyte ratio (NLR) [12], platelet/ histological grade, tumor size, and lymph node(LN)
lymphocyte ratio (PLR) [16], C-reactive protein metastasis were collected from medical records.
albumin (CRP/Alb) ratio [13], modified Glasgow Patients with International Federation of Gynecology
prognostic score (mGPS) [14], prognostic index (PI) and Obstetrics (FIGO) 2009 stage I (IA 17, IB1 89, IB2
[12] and prognostic nutritional index (PNI) [15]. 35), stage II (IIA 47, IIB 28), and stage III/IV (III 12, IV
Among these biomarkers, white cell counts and mGPS 1) cancer were included in this retrospective analysis.
were previously used as inflammatory parameters to Overall survival (OS) was defined as the time from
predict survival of cervical cancer patients, and the date of the diagnosis until the date of death, or the
demonstrated that NLR and mGPS were related to date of the last follow-up. Patient follow-up was
survival prognosis in patients with cervical cancer. completed up to January 21, 2016.
The CRP/Alb ratio as a novel prognostic
markers has been reported in hepatocellular

http://www.jcancer.org
Journal of Cancer 2018, Vol. 9 1879

Nutritional and inflammatory parameters two-sided, and a p value less than 0.05 was considered
All the samples were collected at the time of statistically significant.
diagnosis before any treatment, including white cells,
neutrophils, lymphocytes, platelets, level of serum
Results
CRP, albumin concentration and SCC-Ag level. The Patient Characteristics
count of white blood cells, neutrophils, lymphocyte
A total of 229 patients were enrolled in our
and platelets were collected by an automated hema-
study. The overall median age was 44 years (age
tology system (Sysmex XE-5000, Kobe, Japan). CRP
range, 28 to 79 years), the median survival time was
and albumin were measured by an automatic bioche-
83 months, and the actuarial 7-year survival rate was
mical analyzer (Hitachi 7600, Tokyo, Japan). SCC-Ag
79.0%. More than half of the patients were diagnosed
was measured using a chemiluminescence micro-
at early stages (IA to IIA = 188/229, 82.1%) and with
particle immunoassay (Abbott Architect i2000, USA).
negative LN metastasis (184/229, 80.3%). Among all,
CRP/Alb ratio was defined as the serum CRP level
115 (G1 and G2, 50.2 %) patients were classified into
divided by the serum Alb level. NLR was defined as
the well-differentiated carcinoma category and 114
the neutrophil count divided by lymphocyte count.
(G3, 49.8%) patients were classified into the poor
PLR was defined as the absolute platelet count
undifferentiated carcinoma category. Most of them
divided by the absolute lymphocyte count. mGPS
received radical surgery as first-line treatment
consists of serum CRP and albumin levels (mGPS 2:
(203/229, 88.6%), and 153 of them underwent
CRP >10 mg/L and albumin <35 g/L; mGPS 1: CRP
chemotherapy and(or) radiotherapy after surgery.
>10 mg/L and albumin > 35 g/L; mGPS 0: CRP ≤10
The baseline characteristics and parameters of the 229
mg/L). PI: 0 for CRP 10 mg/L or less and white cell
patients are shown in Table 1.
count 11×109/L or less, 1 if one of the two markers
was higher, 2 if both of them were higher. PNI was Univariate Survival Analysis of All Prognostic
calculated by the formula Alb (g/L) + 5×lymphocyte Parameters
count×109/L: 0 for PNI > 45; 1 for PNI ≤ 45 [16]. In order to investigate the prognostic value of
The optimal cutoff prognostic values for CRP/Alb ratio and other prognostic factors, we
CRP/Alb ratio, NLR and PLR performed survival analysis in cervical cancer and
SCC subgroup. The univariate analysis results (Table
The best cut-off value was determined by
1) showed that FIGO stages, tumor size, LN,
minimum P-value approach [17]. The CRP/Alb ratio
treatments, CRP, CRP/Alb ratio, NLR, PLR, mGPS, PI
cutoff point for cervical cancer specific survival was
and SCC-Ag were significantly associated with OS in
0.022 (40th percentile value) with the maximum χ2
all patients, but in SCC subgroup, tumor size and PLR
log-rank value of 9.181 (p = 0.002), and all patients
were not clear.
were divided into either high or low CRP/Alb ratio
group. NLR cutoff 1.60 (33th percentile value) and Multivariate Analysis of All Prognostic
PLR cutoff 149.27 (66th percentile value) were selected Parameters
as optimal cutoff level for assessing OS (χ2 = 6.830, p = All prognostic factors with p less than 0.05 in
0.009, and χ2 = 5.544, p = 0.019, respectively) to divide univariate analysis underwent multivariate analysis
the patients into high or low risk subsets. (Table 1). FIGO stages [HR = 2.36 (95% CI:1.02-5.47), p
Statistical Analysis = 0.001], LN metastasis [HR = 0.47 (95% CI: 0.26-0.85),
p = 0.013], treatments [HR = 2.77 (95% CI: 1.56-4.91), p
Statistical analyses were using SPSS 19.0
= 0.001] and NLR [HR = 2.47 (95% CI: 1.15-5.31), p =
statistical software package (SPSS Inc., Chicago, IL,
0.020] were independently associated with all patients
USA). Variables with significant prognostic value on
OS. Besides, LN metastasis [HR = 0.41 (95% CI:
univariate analysis were selected for multivariable
0.22-0.78), p = 0.008], treatments [HR = 2.72 (95% CI:
Cox regression analysis adopting the forward
1.46-5.07), p = 0.002], CRP/Alb ratio [HR = 2.36 (95%
stepwise method. The survival curves were plotted by
CI:1.02-5.47), p = 0.045] and NLR [HR = 2.28 (95% CI:
the Kaplan-Meier method and compared with
1.05-4.97), p = 0.038] were identified to be
log-rank test. Chi-Square or Fisher’s exact test was
independent prognostic factors for OS in SCC.
used to compare the categorical variables. The
Kaplan–Meier survival curves according to
association between NLR and CRP/Alb Ratio was
stratified by CRP/Alb ratio (Fig. 1 a and d) and NLR
analyzed by Spearman’s rank correlation. Receiver
(Fig. 1 b and e) revealed that the presence of systemic
operating characteristics (ROC) curves and the areas
inflammatory response as elevated NLR and
under the curve (AUC) were used to evaluate the
CRP/Alb ratio was unprofitable for survival of all and
discriminatory ability. All reported p values were
SCC patients. CRP/Alb ratio dichotomisation showed

http://www.jcancer.org
 Journal of Cancer 2018, Vol. 9 1880

the greater survival difference than NLR (74% high vs Methods combining CRP/Alb ratio with NLR might
89% low), with a 7-year survival rate of 72% (CRP/ improve patient stratification in relation to OS. Thus,
Alb-high) vs 90% (CRP/Alb-low) in all patients. These we stratified patients into three groups: (a) NLR-low
results were echoed in the SCC subgroup with and CRP/Alb-low, (b) NLR-high or CRP/Alb -high
estimated cumulative 7-year survival rate of 71% and (c) CRP/Alb-high and NLR-high (Fig. 1 c and f),
(CRP/Alb-high) vs 91% (CRP/Alb-low) and NLR corresponding to low, intermediate and high risk
(74% high and 88% low). groups. The cumulative 7-year OS rate in the 229
Prognostic Significance of the Combined Index patients was 97%, 84% and 68% respectively, and in
CRP/Alb ratio and NLR SCC subgroup was 97%, 83% and 68% respectively.
Further analysis of the relation between When adjusted for other prognostic factors in the
CRP/Alb ratio and NLR was performed using the multivariate analysis (Table 1), both the high and
Spearman’s rank correlation analysis. The results intermediate risk groups had significantly poor
showed that the CRP/Alb ratio was positively prognosis than the low risk group.
associated with NLR (r = 0.235, p < 0.001) (Fig. 2).

Table 1. Pretreatment inflammatory parameters for overall survival indentified by univariate and multivariate analyses
All patients (n=229) SCC group (n=198)
Characteristic Univariate analysis Multivariate analysis Univariate analysis Multivariate analysis
HR (95 % CI) p value HR (95 % CI) p value HR (95 % CI) p value HR (95 % CI) p value
Age(years)
< 44/≥ 44 1.50(0.82-2.74) 0.185 1.65(0.86-3.17) 0.135
FIGO stages
Ⅰ/Ⅱ/Ⅲand Ⅳ 3.26(2.20-4.81) <0.001* 2.13(1.38-3.27) 0.001* 2.81(1.84-4.29) <0.001* 1.58(0.99-2.55) 0.058
Histologic typing
Sqc/ Adc/ Asc 0.80(0.38-1.67) 0.551
Histologic grade
G1 and G2/ G3 1.44(0.81-2.56) 0.210 1.55(0.83-2.89) 0.170
Tumor size, cm
< 4/≥4 2.10(1.18-3.75) 0.012* 1.80(0.96-3.38) 0.069
LN metastasis
No/ Yes 0.30(0.17-0.54) <0.001* 0.47(0.26-0.85) 0.013* 0.30(0.16-0.55) <0.001* 0.41(0.22-0.79) 0.008*
Treatments
Sur / Sur and Che and(or) Rad/ Che and 4.28(2.55-7.18) <0.001* 2.77(1.56-4.91) 0.001* 3.80(2.18-6.64) <0.001* 2.72(1.46-5.07) 0.002*
(or) Rad
NLR
≤ 1.60/> 1.60 2.64(1.24-5.64) 0.012* 2.47(1.15-5.31) 0.020* 2.51(1.16-5.42) 0.019* 2.28(1.05-4.97) 0.038*
PLR
≤ 149.27 / > 149.27 1.95(1.10-3.43) 0.021* 1.64(0.89-3.01) 0.115
Neutrophil count(×109/L)
≤ 7.0/> 7.0 2.11(0.94-4.70) 0.069 2.36(0.99-5.61) 0.052
CRP(mg/L)
≤ 10.0/> 10.0 3.02(1.41-6.46) 0.004* 3.03(1.34-6.82) 0.008*
Alb(g/L)
≥35.0/ <35.0 0.602(0.08-4.36) 0.615
CRP/Alb
≤ 0.022/> 0.022 3.18(1.54-6.57) 0.002* 3.49(1.55-7.85) 0.003* 2.36(1.02-5.47) 0.045*
mGPS
0/1/2 3.02(1.41-6.46) 0.004* 3.03(1.34-6.82) 0.008*
PI
0/1/2 1.82(1.13-2.92) 0.013* 1.95(1.16-3.27) 0.011*
PNI
0/1 2.30(0.56-9.50) 0.248 2.29(0.55-9.49) 0.252
SCC-Ag
≤ 1.5/> 1.5 2.40(1.35-4.27) 0.003* 2.84(1.50-5.40) 0.001*
NLR+CRP/Alb
NLR-low+CRP/Alb-low/NLR-high or 2.72(1.63-4.54) <0.001* 2.22(1.30-3.80) 0.003* 2.63(1.54-4.48) <0.001* 2.32(1.32-4.07) 0.003*
CRP/Alb-high/NLR-high+CRP/Alb-high
*Statistically significant prognostic factor identified by univariate/multivariate analysis.
Abbreviation: FIGO: International Federation of Gynecology and Obstetrics, Sqc: Squamous carcinoma, Adc: Adenocarcinoma, Asc: Adenosquamous carcinoma, LN lymph
node, Sur: Surgery, Che: chemotherapy, Rad: radiotherapy, NLR: neutrophil lymphocyte ratio, PLR: platelet lymphocyte ratio, CRP: C-reactive protein, WBC: white blood
cell. CRP/Alb: C-reactive protein/Albumin ratio, mGPS: modified Glasgow prognostic score, PI: Prognostic index, PNI: Prognostic nutritional index, SCC-Ag: squamous cell
carcinoma -related antigen, HR: hazard ratio, CI: confidence interval.
NLR, CRP/Alb and combined NLR+ CRP/Alb were adjusted separately in multivariable models. Results from the multivariable model which included combined NLR +
CRP/Alb score are indicated in bold. The cut-off values for CRP/Alb, NLR and PLR were determined by the method described in statistic analysis. CRP, neutrophil count
and SCC-Ag were categorized according to clinical normal reference range.

http://www.jcancer.org
 Journal of Cancer 2018, Vol. 9 1881

Fig. 1 Prognosis significance of NLR, CRP/Alb ratio in all cervical cancer and SCC subgroup. The 7-year OS rate was calculated by the Kaplan–Meier
method and analyzed by the log-rank test. (a, d) OS based on NLR in all patients and SCC patient. (b, e) OS based on CRP/Alb ratio in all patients and SCC patient.
(c, f) OS of combined NLR and CRP/Alb ratio-based categorisation in all patients and SCC patient.

0.028), although weakly correlated as a continuous

variable (Spearman’s rho coefficient 0.179; p = 0.011).
However, NLR was not associated with age, FIGO
stages, histological grade, tumor size, and LN
metastasis. An elevated CRP/Alb ratio (p > 0.022) was
significantly associated with older patients (p < 0.001),
more advanced FIGO stages (p < 0.001) and high
SCC-Ag concentration (p < 0.001). CRP/Alb ratio also
significantly correlated with age and SCC-Ag as a
continuous variable (Spearman’s rho coefficient 0.325
and 0.348 respectively; both p < 0.001).

Discussion
In this study, we investigated the prognostic
value of eight clinicopathological variables (age, FIGO
stages, histological typing, histological grade, tumor
Fig. 2 Correlation of serum NLR and CRP/Alb ratio in 229 patients size, LN metastasis treatment methods and SCC-Ag)
with cervical cancer. The Pretreatment NLR was positive correlation with and 10 systemic inflammatory parameters in cervical
CRP/Alb ratio (r = 0.235, p < 0.001).
cancer and SCC subgroup. Our results showed that
CRP and CRP/Alb ratio was a prognostic factor for
OS in cervical cancer, but not an independent
Associations between NLR and CRP/Alb Ratio
prognostic factor. However, it resulted to be an
with Clinicopathological Factors of Patient
importantly independent prognostic factor for OS in
with SCC
SCC subgroup. Barbara analysed prognostic value of
The clinicopathological characteristics of patients serum CRP in rare histological subtype
based on NLR and CRP/Alb ratio are shown in Table adenocarcinoma of the uterine cervix. They find that
2. NLR was statistically associated with SCC-Ag (p =

http://www.jcancer.org
 Journal of Cancer 2018, Vol. 9 1882

CRP level can be seen as an additional independent large-scale prospective validation should be
prognostic parameter in patients with the rare performed in non-SCC group.
histological subtype adenocarcinoma of the uterine mGPS was calculated with CRP and albumin
cervix [11]. CRP/Alb was convenient for testing in (same as CRP/Alb ratio), which has been reported to
clinical laboratories [18], and it was a sensitive, be a good prognostic marker in various cancers.
reliable convenient and a low-cost prognostic marker Although the multivariate analysis showed that
in cervical cancer. In addition, we found that mGPS was not an independent prognostic factor both
combined NLR and CRP/Alb ratio could enhance the in cervical cancer and SCC group, the comparison of
prognostic value in patients with cervical cancer. AUC value identified no differences in the
discriminatory ability between mGPS and CRP/Alb
Table 2. Associations of NLR and CRP/Alb ratio with ratio (Supplementary Fig. 1). Polterauer et al also
clinicopathological factors of 198 patient with SCC demonstrated that mGPS can be used as a survival
predictor in cervical cancer [21]. What further caught
Characteristic NLR, n p value CRP/Alb ratio, n p value
≤ 1.60 > 1.60 ≤ 0.022 > 0.022 our attention was that when classified by the mGPS
Age(years) 0.343 < 0.001* 92.0% of patients were classified in the group of a 0
< 44 31 49 43 37 score in our study while 72.5% in Polterauer [21],
≥ 44 38 80 33 85
FIGO stages
suggesting that mGPS could not distinguish the
0.699 < 0.001*
Ⅰ 45 76 62 59 survival differences of most of the patients. As a
Ⅱ 21 45 14 52 continuous variable, CRP/Alb ratio might have the
Ⅲand Ⅳ 3 8 0 11 ability to identify slight differences among patients
Histologic grade 0.741 0.892
G1/G2 32 63 36 59
classified into the same group by the mGPS score.
G3 37 66 40 63 Therefore CRP/Alb might be a more significant
Tumor size, cm 0.240 0.461 inflammation-related factors than the mGPS to
<4 55 93 59 89
predict survival.
≥4 14 36 17 33
LN metastasis 0.551 0.275
In addition, an elevated NLR was independently
No 57 102 64 95 associated with poor OS in 229 patients with cervical
Yes 12 27 12 27 cancer, even in SCC subgroup. This observation
Treatments 0.030* 0.027*
further supported the correlation between chronic
Surgery alone 19 20 21 18
Surger and 46 89 50 85 inflammation and poor OS in cancer patients. Our
chemotherapy finding of positive association between elevated NLR
and(or) radiotherapy
and poor prognosis was consistent with the results
Chemotherapy 4 20 5 19
and(or) radiotherapy obtained from 1061 cervical cancer patients in Korea
SCC-Ag 0.028* < 0.001* [22]. However, Zhang et al found that NLR was an
≤ 1.5 46 65 58 53
independent prognostic marker for progression-free
>1.5 23 64 18 69
p values were calculated by Chi-Square ( χ2 test) or Fisher’s exact test, * p < 0.05
survival, but not for OS of patients with cervical
considered as statistically significant. cancer treated with initial radical surgery [23].
Abbreviations: FIGO International Federation of Gynecology and Obstetrics, LN Furthermore, Wang et al found that NLR is not
lymph node, NLR the neutrophil lymphocyte ratio, CRP/Alb the C-reactive
protein/Albumin ratio, SCC-Ag squamous cell carcinoma -related antigen. associated with the survival of cervical cancer patients
treated with neoadjuvant chemotherapy and radical
Low serum albumin level is correlated with hysterectomy [24]. The possible reason was due to the
malnutrition and weight loss and it is a risk factor for treatment methods, which triggered host
cancer mortality. However, our finding of a negative inflammatory response, immune response, and their
association between serum CRP or albumin and imbalance. The results in our study also showed the
prognosis on multivariate analysis is the opposite to prognostic significance of NLR according to different
the findings of another studies [19-20]. This is due to treatment methods by the Kaplan-Meier method and
the fact that our study included various analyzed by the log-rank test (Supplementary Fig. 2).
inflammation-related factors to evaluate a prognostic Spearman's rank correlation analysis revealed
value in cervical cancer, which can better represent that NLR was positively correlated with CRP/Alb
the inflammatory conditions of patients. In general, ratio. The biological mechanism justifying the chronic
merging CRP and albumin into a new index might inflammation role in cancer is yet to be elucidated. It
have a prognostic value in inflammation, and better is well known that cervical cancer not only can
predict SCC patients OS. In all cervical cancer develop at sites of inflammation subsequent to human
patients, CRP/Alb ratio was not an independent papillomavirus infection, but can also trigger regional
prognostic factor, which might be due to the small inflammatory responses, releasing proinflammatory
samples number of non SCC patients. Thus, a cytokines around the tumor that result in

http://www.jcancer.org
Journal of Cancer 2018, Vol. 9 1883

inflammatory microenvironment [25]. IL-6, as an Our study had several limitations. The results are
important proinflammatory cytokine, stimulate the based on single-center. Patients’ number in some
production of CRP and the production of neutrophils subgroups is small. This study was focused on
in the bone marrow, which is important for tumor Chinese population. Since cancer distribution is
angiogenesis [26]. Since we observed a strong influenced by population, gender and geographic
correlation between NLR and CRP/Alb ratio, this locations, it is problematic to associate our results to
phenomenon showed the complex interaction other ethnic groups.
between the host immune system and the In conclusion, our study demonstrated that
inflammatory tumor microenvironment, potentially CRP/Alb ratio was a precise, convenient and
influencing patient survival [27]. inexpensive prognostic marker in cervical cancer,
Combined NLR and CRP/Alb ratio resulted in especially in case of SCC patients. In addition, the
the lowest 7-year survival ratio of the patient with combination between CRP/Alb ratio and NLR could
CRP/Alb-high and NLR-high among the three be used to better predict prognosis in patients with
groups. These results add further support to the fact cervical cancer.
that cervical cancer is related to systemic
inflammatory response and nutritional decline, with Supplementary Material
subsequent poor outcome. These results further Supplementary figures.
demonstrated the positive relationship between NLR http://www.jcancer.org/v09p1877s1.pdf
and CRP/Alb ratio. Moreover, they highlighted the
prognostic effect of combining NLR and CRP/Alb Acknowledgements
ratio. The prognostic value of combined CRP/Alb We thank the staff at the Director of Clinical
ratio and NLR should be further evaluated in a larger Laboratories, Sun Yat-sen University Cancer Center
number of patients. for providing support on research conditions in this
In our study, NLR and CRP/Alb ratio were study.
associated with SCC-Ag concentration in SCC group.
These results indicated that inflammation might be Author contribution
correlated with SCC-Ag. It has been reported that in H.C. and S.-L.C. proposed, designed and revised
asthma, a chronic airway inflammatory disease, both the article. X.H. and J.-P.L. designed, summarized
SCC-Ag 1 and SCC-Ag 2 are induced by two related data and revised this article. X.-H.L., J.-P.Z. and
Th2-type cytokines, IL-4 and IL-13, and that SCC-Ag Q.-Y.Z. collected articles, summarized data, did
expression is increased in bronchial asthma patients statistical work and drafted the manuscript. All
[28-29]. However, it is unclear whether the chronic authors reviewed this manuscript and approved the
inflammation, which is reflected by elevated NLR and final draft.
CRP/Alb ratio, can influence SCC-Ag expression in
cervical cancer. Further studies are needed to clarify Competing Interests
this aspect. The authors have declared that no competing
Besides determining a prognostic value of interest exists.
inflammation-related factors, we correlated NLR and
CRP/Alb ratio with clinicopathological parameters in References
SCC group. On the one side, we found that elevated 1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortettieulent J, Jemal A. Global cancer
statistics, 2012. Ca A Cancer Journal for Clinicians. 2015; 65: 87.
CRP/Alb ratio was associated with old patients and 2. Quinn MA BJ, Odicino F, Maisonneuve P, Beller U, Creasman WT, Heintz AP,
more advanced FIGO stages. The results might be Ngan HY, Pecorelli S. Carcinoma of the cervix uteri. FIGO 26th Annual Report
on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet.
explained by the following reasons: (1) Albumin was 2006; Nov: 61.
correlated with the patient's physical conditions. 3. Ferrandina G, Legge F, Fagotti A, Fanfani F, Distefano M, Morganti A, et al.
Preoperative concomitant chemoradiotherapy in locally advanced cervical
Malnutrition is common in old patients [30]. (2) Serum cancer: safety, outcome, and prognostic measures. Gynecologic Oncology.
CRP levels are correlated with tumor stages in various 2007; 107: S127-S32.
4. Rosa DD, Medeiros LR, Edelweiss MI, Bozzetti MC, Pohlmann PR, Stein AT, et
cancers including cervical cancer. The higher the al. Adjuvant platinum-based chemotherapy for early stage cervical cancer:
tumor stage, the greater the inflammatory response 5.
John Wiley & Sons, Ltd; 2009.
Petignat P, Loubeyre P. Should we modify the current FIGO staging system
and the higher the CRP serum leve. (3) for early-stage cervical cancer? Expert Review of Anticancer Therapy. 2008; 8:
1015-7.
Hypoalbuminemia is suggested to predict progressive 6. Brenner DE, Whitley NO, Prempree T, Villasanta U. An evaluation of the
nutritional decline of patients with advanced cancer computed tomographic scanner for the staging of carcinoma of the cervix.
cancer. 1982; 50: 2323-8.
[31]. Older age and more advanced FIGO stages are 7. Sturgeon CM, Duffy MJ, Hofmann BR, Lamerz R, Fritsche HA, Gaarenstroom
both traditionally poor predictors of patients with K, et al. National Academy of Clinical Biochemistry Laboratory Medicine
Practice Guidelines for use of tumor markers in liver, bladder, cervical, and
cancer, which further support that elevated CRP/Alb gastric cancers. Clinical Chemistry. 2010; 56: 1-48.
ratio was associated with poor performance status.

http://www.jcancer.org
 Journal of Cancer 2018, Vol. 9 1884
8. Lee YY, Choi CH, Sung CO, Do IG, Huh S, Song T, et al. Prognostic value of
pre-treatment circulating monocyte count in patients with cervical cancer:
comparison with SCC-Ag level. Gynecologic Oncology. 2012; 124: 92.
9. Gadducci A, Tana R, S, Genazzani A. The serum assay of tumour markers in
the prognostic evaluation, treatment monitoring and follow-up of patients
with cervical cancer: a review of the literature. Critical Reviews in
Oncology/hematology. 2008; 66: 10-20.
10. Reesinkpeters N, Van dVJ, Ten Hoor KA, Boezen HM, de Vries EG, Schilthuis
MS, et al. Preoperative serum squamous cell carcinoma antigen levels in
clinical decision making for patients with early-stage cervical cancer. Journal
of clinical oncology. 2005; 23: 1455-62.
11. Bodner-Adler B, Kimberger O, Schneidinger C, Kölbl H, Bodner K. Prognostic
Significance of Pre-treatment Serum C-Reactive Protein Level in Patients with
Adenocarcinoma of the Uterine Cervix. Anticancer research. 2016; 36: 4691.
12. Kasymjanova G, Macdonald N, Agulnik JS, Cohen V, Pepe C, Kreisman H, et
al. The predictive value of pre-treatment inflammatory markers in advanced
non-small-cell lung cancer. Current Oncology. 2010; 17: 52-8.
13. Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, et al. The
C-Reactive Protein/Albumin Ratio, a Novel Inflammation-Based Prognostic
Score, Predicts Outcomes in Patients with Hepatocellular Carcinoma. Annals
of surgical oncology. 2015; 22: 803-10.
14. Proctor M, Morrison D, Talwar D, Balmer S, O'reilly D, Foulis A, et al. An
inflammation-based prognostic score (mGPS) predicts cancer survival
independent of tumour site: a Glasgow Inflammation Outcome Study. British
journal of cancer. 2011; 104: 726.
15. Buzby GP, Mullen JL, Matthews DC, Hobbs CL, Rosato EF. Prognostic
nutritional index in gastrointestinal surgery. American Journal of Surgery.
1980; 139: 160-7.
16. Wang D, Luo H, Qiu M, Wang Z, Zhang D, Wang F, et al. Comparison of the
prognostic values of various inflammation based factors in patients with
pancreatic cancer. Medical Oncology. 2012; 29: 3092-100.
17. Galon J, Costes A, Sanchezcabo F, Kirilovsky A, Mlecnik B, Lagorcepagès C, et
al. Type, Density, and Location of Immune Cells Within Human Colorectal
Tumors Predict Clinical Outcome. Science. 2006; 313: 1960-4.
18. Póvoa P. C-reactive protein: a valuable marker of sepsis. Intensive Care
Medicine. 2002; 28: 235-43.
19. Polterauer S, Grimm C, Zeillinger R, Heinze G, Tempfer C, Reinthaller A, et al.
Association of C-reactive protein (CRP) gene polymorphisms, serum CRP
levels and cervical cancer prognosis. Anticancer research. 2011; 31: 2259.
20. Polterauer S, Grimm C, Tempfer C, Sliutz G, Speiser P, Reinthaller A, et al.
C-reactive protein is a prognostic parameter in patients with cervical cancer.
Gynecologic Oncology. 2007; 107: 114-7.
21. Polterauer S, Grimm C, Seebacher V, Rahhal J, Tempfer C, Reinthaller A, et al.
The inflammation-based Glasgow Prognostic Score predicts survival in
patients with cervical cancer. International Journal of Gynecological Cancer
Official Journal of the International Gynecological Cancer Society. 2010; 20:
1052-7.
22. Lee YY, Choi CH, Kim HJ, Kim TJ, Lee JW, Lee JH, et al. Pretreatment
neutrophil:lymphocyte ratio as a prognostic factor in cervical carcinoma.
Anticancer research. 2012; 32: 1555.
23. Zhang Y, Wang L, Liu Y, Wang S, Shang P, Gao Y, et al. Preoperative
neutrophil-lymphocyte ratio before platelet-lymphocyte ratio predicts clinical
outcome in patients with cervical cancer treated with initial radical surgery.
International Journal of Gynecological Cancer Official Journal of the
International Gynecological Cancer Society. 2014; 24: 1319.
24. Wang D, Wu M, Feng FZ, Huang HF, Yang JX, Shen K, et al. Pretreatment
neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios do not predict
survival in patients with cervical cancer treated with neoadjuvant
chemotherapy and radical hysterectomy. Chin Med J (Engl). 2013; 126: 1464-8.
25. Deivendran S, Marzook KH, Pillai MR. The role of inflammation in cervical
cancer. Inflammation and Cancer: Springer; 2014. p. 377-99.
26. Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH. Platelets and
granulocytes, in particular the neutrophils, form important compartments for
circulating vascular endothelial growth factor. Angiogenesis. 2003; 6: 283.
27. Mcmillan DC. Systemic inflammation, nutritional status and survival in
patients with cancer. Current Opinion in Clinical Nutrition & Metabolic Care.
2009; 12: 223.
28. Sakata Y, Arima K, Takai T, Sakurai W, Masumoto K, Yuyama N, et al. The
squamous cell carcinoma antigen 2 inhibits the cysteine proteinase activity of a
major mite allergen, Der p 1. Journal of Biological Chemistry. 2004; 279: 5081.
29. Izuhara K. The role of interleukin-4 and interleukin-13 in the
non-immunologic aspects of asthma pathogenesis. Clinical Chemistry &
Laboratory Medicine Cclm. 2003; 41: 860.
30. Viera K, Jaroslav R, Maria G, Adrian K. Ten-year all-cause mortality in
hospitalized non-surgical patients based on nutritional status screening.
Public Health Nutrition. 2015; 18: 2609-14.
31. Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, et al.
Prognostic effect of weight loss prior to chemotherapy in cancer patients.
Eastern Cooperative Oncology Group. American Journal of Medicine. 1980;
69: 491.

http://www.jcancer.org