The C-reactive protein/albumin ratio predicts overall survival of patients with advanced pancreatic cancer
The C-reactive protein/albumin ratio predicts overall survival of patients with advanced pancreatic cancer
Mengwan Wu 0
Jing Guo 0
Lihong Guo 0
Qiang Zuo 0
0 Department of Oncology, Nanfang Hospital, Southern Medical University , 1838 North Guangzhou Avenue, Guangzhou, Guangdong Province 510515 , China
Recent studies have demonstrated the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in cancer. However, the role of the CRP/Alb ratio in advanced pancreatic cancer (PC) has not been examined. A retrospective study of 233 patients with advanced PC was conducted. We investigated the relationship between the CRP/Alb ratio, clinicopathological variables, and overall survival (OS). The optimal cutoff point of the CRP/Alb ratio was 0.54. A higher CRP/Alb ratio was significantly associated with an elevated neutrophil-lymphocyte ratio (NLR) (P < 0.001) and higher modified Glasgow prognostic score (mGPS) (P < 0.001). Using univariate analyses, we found that the age (P = 0.009), disease stage (P < 0.001), NLR (P < 0.001), mGPS (P < 0.001), and CRP/Alb ratio (P < 0.001) were significant predictors of OS. Patients with a higher CRP/Alb ratio had a worse OS than patients with a lower CRP/Alb ratio (hazard ratio (HR) 3.619; 95 % CI 2.681-4.886; P < 0.001). However, the CRP/Alb ratio was identified as the only inflammation-based parameter with an independent prognostic ability in the multivariate analyses (P < 0.001). The pretreatment CRP/Alb ratio is a superior prognostic and therapeutic predictor of OS in advanced PC.
Advanced pancreatic cancer; Inflammation; CRP/Alb ratio; Prognostic score; Survival
Pancreatic cancer ranks as the 12th most commonly diagnosed
cancer and seventh leading cause of cancer death; there are an
estimated 337,900 new cases and 330,400 deaths occurring in
2012 worldwide . Most patients are diagnosed at an
advanced stage and have a rapid clinical decline, culminating
in death within less than 1 year after diagnosis. The high
mortality is associated with a limited chance of curative
resection at the time of diagnosis, as surgical resection offers the
only prospect of long-term survival or cure. Moreover, one
study showed that the median survival in patients with
curative resection was 14.9 months longer than in those with an
advanced stage (19.1 vs 4.2 months). Similarly, the 5-year
survival rates were higher in the operable patients (19.3 vs
0.8 %) . Although surgical resection has improved the
prognosis of pancreatic cancer patients, it continues to have
a poor prognosis.
Currently, although continuous advances in modern
diagnostic imaging have been achieved, most established
prognostic factors continue to rely on surgical
exploration, such as the tumor size, histologic grade, and vascular
and nodal involvement. Many patients at an advanced
stage also undergo a morbid operative procedure during
the course of pancreatic lesion evaluation. Therefore, it is
important to identify some easily obtainable and reliable
prognostic factors for better risk stratification and optimal
treatment plans. With the increasing number of studies
suggesting that tumor-elicited inflammation plays a key
role in malignant transform and tumor progression [3–6],
some inflammation-based prognostic factors have been
explored in many cancers during the course from bench
to bedside. These factors are all easily available from
peripheral blood samples, including the
neutrophillymphocyte ratio (NLR), platelet-lymphocyte ratio
(PLR), white cell count and C-reactive protein (CRP)
combined into the prognostic index (PI), albumin and
lymphocyte count in the prognostic nutritional index
(PNI), and CRP- and albumin-based factors of the
modified Glasgow prognostic score (mGPS) and C-reactive
protein/albumin (CRP/Alb) ratio [7–12]. Among these
indicators, the CRP/Alb ratio has been reported as a novel
reliable marker in different cancers such as lung, liver,
gastric, and esophageal cancer [8, 13–16]. However, the
role of the CRP/Alb ratio in patients with advanced
pancreatic cancer has not previously been elucidated.
In this retrospective study, we examined the prognostic
value of the CRP/Alb ratio and compared it to other
established inflammation-based prognostic scores.
Materials and methods
We enrolled 233 patients who were diagnosed with advanced
pancreatic cancer in Nanfang Hospital of Southern Medical
University (Guangzhou, Guangdong Province, China)
between January 2011 and December 2014. All medical records
were retrospectively reviewed. The following inclusion
criteria were used: (1) cytologically or histologically
diagnosed as pancreatic adenocarcinoma; (2) survival of at least
30 days after diagnosis; (3) confirmed stage III or IV based on
the AJCC/UICC TNM staging system (the 7th edition); and
(4) pretreatment laboratory data were available. Patients
suffering from detectable acute inflammation were excluded.
Selected patients were carefully followed up after pathological
diagnosis until September 30, 2015, or death from any cause.
Clinical data collection
Baseline characteristics were obtained from the electronic
medical record system, including the age; gender; tumor
location and stage; pretreatment laboratory counts of white
cells, neutrophils, lymphocytes, and platelets; tumor markers
( c a r c i n o e m b r y o n i c a n t i g e n 1 9 - 9 , C A 1 9 - 9 , a n d
carcinoembryonic antigen (CEA)); levels of CRP and
albumin; and therapeutic information. Based on previous studies,
the CRP/Alb ratio was calculated by dividing the serum
CRP level by the serum albumin level . The mGPS
combined the CRP and albumin concentrations. Patients
who had both elevated CRP (>1 mg/dl) and decreased
albumin levels (<3.5 g/dl) were assigned a score of 2. Patients
with only elevated CRP (>1 mg/dl) were assigned a score of
1, and patients with neither of these abnormalities were
assigned a score of 0 . NLR and PLR were both
Table 1 Clinicopathological characteristics of patients with pancreatic
cancer (n = 233)
CRP/Alb C-reactive protein/albumin, NLR neutrophil-lymphocyte ratio,
PLR platelet/lymphocyte ratio, mGPS the modified Glasgow prognostic
score, CA19-9 carbohydrate antigen 19-9, CEA carcinoembryonic
categorized into two groups according to the cutoff values
of >5 and >150, respectively [19, 20].
Comparisons between groups were performed using the
chisquare test. The optimal cutoff value of the CRP/Alb ratio was
determined using a web-based system, R
softwareengineered, which was designed by Budczies J et al.
(http://molpath.charite.de/cutoff/) . The overall survival
(OS) was measured from the day of pathological diagnosis
to death from any cause or the final date of follow-up. The
OS curves were generated using the Kaplan–Meier method,
and differences between groups were compared using the
logrank test. Prognostic variables that were significant in
univariate analyses were selected for multivariate Cox proportional
hazard model analyses using the forward stepwise method.
Statistical analyses were performed with SPSS 21.0 (IBM
Corporation, Armonk, NY, USA). A two-sided P value
<0.05 was considered statistically significant.
A total of 233 patients who were diagnosed with advanced
pancreatic cancer in Nanfang Hospital were evaluated. They
had a median age of 62 years (range 26–85). Among these
patients, 156 (67.0 %) were males and 77 (33.0 %) were
females, while the numbers of patients with locally
advanced and metastasis disease were 83 (35.6 %) and 150
(64.4 %), respectively. Nearly half of patients had a primary
pancreatic head tumor (n = 104, 44.6 %). The pretreatment
blood sample analyses showed that the median CA19-9
levFig. 1 The hazard ratio (HR) for
according to the cutoff points of
the CRP/Alb ratio in patients with
advanced PC. A vertical line
designates the chosen cutoff
point. The plots were generated
using Cutoff Finder
el for the entire group was 427 U/ml, while the CEA was a
median of 3.45 ng/ml. More than two thirds of patients
received gemcitabine monotherapy as first-line treatment
(n = 162, 69.5 %). The baseline characteristics of the 233
patients are shown in Table 1.
Cutoff point determination for the CRP/Alb ratio
The median value of the CRP/Alb ratio was 0.241 (range,
0.002–6.728). The analyses that were performed with the
biostatistical tool Cutoff Finder showed that a wide range of
cutoff points for the CRP/Alb ratio were significant (Fig. 1).
For overall survival, the optimal cutoff point of the CRP/Alb
ratio for stratifying patients with advanced pancreatic cancer
(PC) was 0.54. Based on this result, all patients were
categorized into the CRP/Alb-high (n = 74, 31.8 %) and
CRP/Alblow (n = 159, 68.2 %) groups.
Correlation of the CRP/Alb ratio with clinicopathological
The relationships between the CRP/Alb ratio and other
variables are shown in Table 2. A higher CRP/Alb ratio was
significantly associated with an elevated NLR (P < 0.001) and
higher mGPS score (P < 0.001). In addition, fewer patients in
the high CRP/Alb ratio group received chemotherapy
(P < 0.001) compared to the low CRP/Alb ratio group.
However, there were no significant differences in the age
(P = 0.943), gender (P = 0.103), disease stage (P = 0.200),
tumor location (P = 0.084), PLR values (P = 0.242), CA19-9
levels (P = 0.100), and CEA levels (P = 0.100) between the
CRP/Alb-high and CRP/Alb-low groups.
Table 2 Correlation of the CRP/Alb ratio and clinicopathological
characteristics of PC patients
<0.54, n (%)
≥0.54 n (%)
* Significant differences between patients with the CRP/Alb < 0.54 and
patients with the CRP/Alb ≥ 0.54
Association between the CRP/Alb ratio and OS
The results of the univariate and multivariate analyses are
presented in Table 3. The median survival time of all of the patients
was 4.4 months (95 % CI 4.16–4.58 months), and 227 (97.4 %)
patients died by their final follow-up visit. Based on the cutoff
point of the CRP/Alb ratio, patients were divided into two groups
(<0.54, n = 159 and ≥0.54, n = 74). In the univariate analyses of
survival, the low CRP/Alb ratio group had a longer median
overall survival than the high CRP/Alb ratio group (5.0 vs 2.9 months,
P < 0.001). Additionally, when patients were stratified by disease
stage, the mortality rate of patients with increased C-reactive
protein/albumin ratio (CAR) was also higher in both the locally
advanced subgroup (5.9 vs 4.1 months, P < 0.001) and
metastasis subgroup (4.5 vs 2.4 months, P < 0.001) (Fig. 2).
Univariate analyses also showed that older age (≥62 vs
<62 years, P = 0.009), metastasis stage (metastasis vs locally
advanced, P < 0.001), an elevated NLR (≥5 vs <5, P < 0.001),
higher mGPS scores (1 + 2 vs 0, P < 0.001), and
nonchemotherapeutic treatment (no chemotherapy vs
chemotherapy, P < 0.001) were significantly associated with worse OS in
To investigate whether CRP/Alb ratio could serve as an
independent prognostic factor in advanced PC, multivariate
analyses were also conducted. In the multivariate analyses,
patients in the higher CRP/Alb group had a worse outcome
than those in the lower ratio group (hazard ratio (HR) 3.995;
95 % CI 2.644–6.034; P < 0.001) (Table 3). In addition, the
age (P < 0.001), disease stage (P < 0.001), and chemotherapy
(P < 0.001) independently and significantly predicted OS,
whereas the NLR, PLR, and mGPS did not predict OS
(Table 3 and Fig. 3). Moreover, subgroup analyses were also
conducted. Although patients in the CRP/Alb-high group had
a worse OS than the CRP/Alb-low group, chemotherapy still
contributed to a significantly longer median survival in both
groups (CRP/Alb < 0.54 group, 5.7 vs 3.0 months, P < 0.001;
CRP/Alb ≥ 0.54 group, 3.7 vs 2.0 months, P < 0.001) (Fig. 3).
To identify the interaction between the CRP/Alb ratio and
mGPS for OS, we categorized patients into four groups based
on two indexes, including mGPS score of 1 and CRP/Alb
ratio < 0.54; mGPS score of 1 and CRP/Alb ratio ≥ 0.54;
mGPS score of 2 and CRP/Alb ratio < 0.54; and mGPS score
of 2 and CRP/Alb ratio ≥ 0.54. The survival analyses indicated
that compared with patients who had an mGPS score of 1 and
CRP/Alb ratio ≥ 0.54, those with an mGPS score of 1 and
CRP/Alb ratio < 0.54 had a longer median OS (4.5 vs
3.2 months, P < 0.001), which was similar to the comparison
of an mGPS score of 2 and CRP/Alb ratio < 0.54 with an
mGPS score of 2 and CRP/Alb ratio ≥ 0.54 (4.4 vs 2.4 months,
P = 0.023). However, no significant differences were found
between an mGPS score of 1 and CRP/Alb ratio < 0.54 and an
mGPS score of 2 and CRP/Alb ratio < 0.54 (4.5 vs 4.4 months,
P = 0.370) or between an mGPS score of 1 and CRP/Alb
ratio ≥ 0.54 and an mGPS score of 2 and CRP/Alb ratio ≥ 0.54
(3.2 vs 2.4 months, P = 0.416) (Fig. 4).
Despite recent improvements in the validated benefit of
chemotherapy and spread of multidisciplinary therapy for patients in the
advanced stage, pancreatic cancer remains a devastating disease
with an extremely poor prognosis. Optimal responses will be
achieved only if the treatment plan is tailored for individuals
based on accurate and stable prediction of potential survival.
However, tumor-related parameters such as the pathological
Prognostic factors for overall survival identified by univariate and multivariate analyses
HR (95 % CI)
HR (95 % CI)
stage and resectability of the primary tumor primarily play a role
in evaluating disease and predicting the outcome.
Therefore, an increasing number of thorough studies have
identified some easily available predictors for substituting the
traditional surgical method. A diverse set of observations
offers evidence supporting the correlation between
inflammation and cancer. While early studies were devoted to
elucidating the link between pre-existing inflammation and
consequent tumor initiation, more recent studies tend to add new
insight into tumor-associated inflammation and the host
response to oncogenic change in the intrinsic pathway. For
the intrinsic pathway, inflammation and tumor growth are
driven by genetic mutations that cause the activation of
transcription factors, release of inflammatory mediators
(chemokines, cytokines, and prostaglandins), and subsequent
infiltration of inflammatory cells and angiogenesis . This
inflammatory condition further promotes the malignant
progression of tumors, enhances local immunosuppression,
induces invasion and metastatic spread, and influences the
treatment response [5, 22, 23].
Fig. 2 Kaplan–Meier survival curves showing the difference between the high CRP/Alb ratio and low CRP/Alb ratio groups a in all patients, b in
patients with locally advanced disease, and c in patients with metastatic disease
Among the many inflammatory mediators, interleukin-6
(IL-6) is a notable inflammatory cytokine secreted by innate
immune cells that regulates the levels of C-reactive protein
(CRP), an acute-phase protein . Recently, it was reported
that elevated pretreatment serum IL-6 and CRP levels showed
a significant relationship with a poor outcome [25–28].
Additionally, the serum albumin level is not only a reflection
of nutritional state but also it is, to a larger degree, a
consequence of the inflammatory state. Plausible explanations are
as follows. When considered with tumor-related systematic
inflammation, the ability of the liver to produce albumin
decreases as a result of increased acute-phase protein synthesis
[29, 30]. Alternatively, the release of cytokines from
inflammatory cells increases the microvascular permeability,
increasing the flow of serum albumin towards the extravascular
compartment . Therefore, the link between
hypoalbuminemia and inflammation is also quite strong . Meanwhile,
the role of the pretreatment serum albumin levels as an
independent predictor of the OS has been demonstrated in various
cancers, including PC [33–35].
These achievements greatly piqued our interest in
combining CRP and albumin into a noble potential
inflammatory prognostic indicator in advanced PC and identifying
its predictive value. In addition, some recent studies have
Fig. 3 The overall survival curves according to a disease stage, and b treatment with or without chemotherapy
demonstrated that the CRP/Alb ratio is a promising
inflammation-associated prognostic factor in cancer,
including liver, lung, gastric, and esophageal cancer [8,
13–17]. In our study, we assessed and compared the
prognostic value of the NLR, PLR, mGPS, and CRP/Alb ratio
in advanced PC by retrospectively analyzing the
pretreatment laboratory data of 233 eligible patients. According
to statistical analysis, there was a significant association
between the CRP/Alb ratio and other inflammatory
indexe s ( e x c l u d i n g P L R ) , w h i c h m i g h t s u g g e s t t h a t
Fig. 4 Kaplan–Meier curves between groups based on the mGPS scores and CRP/Alb ratio
comprehensive evaluation of these inflammatory
parameters could provide a more advisable prognostic estimate.
In accordance with the result of the chi-square test of the
CRP/Alb ratio versus disease stage, the CRP/Alb ratio
remained a significant prognostic parameter regardless of
the stage of advanced PC in subgroup analyses. After
excluding the confounding factors from the multivariate
analyses, the CRP/Alb ratio remained the only significant
inflammation-related prognostic index. To the best of our
knowledge, this is the first study to explore the role of the
CRP/Alb ratio as a predictor of prognosis in advanced PC.
As the mGPS and CRP/Alb ratio both include the CRP
and albumin levels, comparison of the two factors was
performed. Because the CRP/Alb ratios of patients with
mGPS scores of 0 were all less than 0.54, dichotomizing
patients with mGPS scores of 1 and 2 on the basis of the
CRP/Alb ratio was conducted. Kaplan–Meier tests
showed that patients with an mGPS score of 1 and CRP/
Alb ratio < 0.54 and an mGPS score of 2 and CRP/Alb
ratio < 0.54 had comparable longer OS. Similarly, those in
the groups with an mGPS score of 1 and CRP/Alb
ratio ≥ 0.54 and an mGPS score of 2 and CRP/Alb
ratio ≥ 0.54 had parallel poor outcome. The results exposed
defects in the mGPS prognostic ability for patients with
scores of 1 and 2 because they did not have significant
differences in OS; by contrast, they could be distinguished
according to the CRP/Alb ratio. This disadvantage arises
from its nature as a categorized variable that fails to
accurately reflect the disease condition of every patient. In
conclusion, the CRP/Alb ratio is superior to the other
inflammation-related prognostic factors. Our findings
may have practical value in the therapy of advanced PC
patients. Patients with a high CRP/Alb ratio may require
more active adjuvant chemotherapy.
The generalizability of the conclusions is limited by the
threatened independence of the variables. As a retrospective
and single-center study, the limitations of the current research
lie in its intrinsic features. To narrow down the inevitable
selection bias, we enrolled consecutive patients and included
a relatively large sample size. Meanwhile, we explored the
prognostic significance of the CRP/Alb ratio in a
multifaceted approach, including validation of the value at the level
of all patients and patient subgroups based on disease stage.
However, a multicenter prospective validation study with a
larger scale sample is needed to confirm our findings.
Compliance with ethical standards
Ethics The study protocol was approved by the ethics committee of
Southern Medical University, and written informed consent for the
utilization of clinical data was obtained from all enrolled patients.
Conflicts of interest None
Open Access This article is distributed under the terms of the
Creative Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted
use, distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a link
to the Creative Commons license, and indicate if changes were made.
1. Torre LA , Bray F , Siegel RL , Ferlay J , Lortet-Tieulent J , Jemal A. Global cancer statistics , 2012 . CA Cancer J Clin . 2015 ; 65 : 87 - 108 .
2. WHO | Mortality . WHO [Internet]. World Health Organization ; 2014 . Available from: http://www.who.int/topics/mortality/en/
3. Grivennikov SI , Greten FR , Karin M. Immunity , inflammation, and cancer. Cell . 2010 ; 140 : 883 - 99 .
4. Allavena P , Garlanda C , Borrello MG , Sica A , Mantovani A. Pathways connecting inflammation and cancer . Curr Opin Genet Dev . 2008 ; 18 : 3 - 10 .
5. Mantovani A , Allavena P , Sica A , Balkwill F. Cancer-related inflammation. Nature . 2008 ; 454 : 436 - 44 .
6. Shalapour S , Karin M. Immunity , inflammation, and cancer: an eternal fight between good and evil . J Clin Invest . 2015 ; 125 : 3347 - 55 .
7. Stotz M , Gerger A , Eisner F , Szkandera J , Loibner H , Ress AL , et al. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer . Br J Cancer . 2013 ; 109 : 416 - 21 .
8. Zhou T , Zhan J , Hong S , Hu Z , Fang W , Qin T , et al. Ratio of Creactive protein/albumin is an inflammatory prognostic score for predicting overall survival of patients with small-cell lung cancer . Nat Publ Group . 2015 ; 5 : 10481 .
9. Gomez D , Farid S , Malik HZ , Young AL , Toogood GJ , Lodge JPA , et al. Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma . World J Surg . 2008 ; 32 : 1757 - 62 .
10. Ni X-C , Yi Y , Fu Y-P , He H-W , Cai X-Y , Wang J-X , et al. Prognostic value of the modified Glasgow prognostic score in patients undergoing radical surgery for hepatocellular carcinoma . Medicine (Baltimore) . 2015 ; 94 :e1486.
11. Hong S , Zhou T , Fang W , Xue C , Hu Z , Qin T , et al. The prognostic nutritional index (PNI) predicts overall survival of small-cell lung cancer patients . Tumour Biol . 2015 ; 36 : 3389 - 97 .
12. Nakamura K , Nishida T , Haruma T , Haraga J , Omichi C , Ogawa C , et al. Pretreatment platelet-lymphocyte ratio is an independent predictor of cervical cancer recurrence following concurrent chemoradiation therapy . Mol Clin Oncol . 2015 ; 3 : 1001 - 6 .
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 . Ann Surg Oncol . 2015 ; 22 : 803 - 10 .
14. Xu X-L , Yu H-Q , Hu W , Song Q , Mao W-M. A novel inflammation-based prognostic score, the C-reactive protein/ albumin ratio predicts the prognosis of patients with operable esophageal squamous cell carcinoma . PLoS One . 2015 ; 10 : e0138657.
15. Wei X-L , Wang F-H , Zhang D-S , Qiu M-Z , Ren C , Jin Y , et al. A novel inflammation-based prognostic score in esophageal squamous cell carcinoma: the C-reactive protein/albumin ratio . BMC Cancer . 2015 ; 15 : 350 .
16. Liu X , Sun X , Liu J , Kong P , Chen S , Zhan Y , et al. Preoperative Creactive protein/albumin ratio predicts prognosis of patients after curative resection for gastric cancer . Transl Oncol . 2015 ; 8 : 339 - 45 .
17. Fairclough E , Cairns E , Hamilton J , Kelly C. Evaluation of a modified early warning system for acute medical admissions and comparison with C-reactive protein/albumin ratio as a predictor of patient outcome . Clin Med (Lond) . 2009 ; 9 : 30 - 3 .
18. Proctor MJ , Morrison DS , Talwar D , Balmer SM , O'Reilly DSJ , Foulis AK , et al. An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study . Br J Cancer . 2011 ; 104 : 726 - 34 .
19. Wang D-S , Luo H-Y , Qiu M-Z , Wang Z-Q , Zhang D-S , Wang F-H , et al. Comparison of the prognostic values of various inflammation based factors in patients with pancreatic cancer . Med Oncol . 2012 ; 29 : 3092 - 100 .
20. Garcea G , Ladwa N , Neal CP , Metcalfe MS , Dennison AR , Berry DP . Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma . World J Surg . 2011 ; 35 : 868 - 72 .
21. Budczies J , Klauschen F , Sinn BV , Gyorffy B , Schmitt WD , DarbEsfahani S , et al. Cutoff Finder: a comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization . PLoS One . 2012 ; 7 : e51862 .
22. Balkwill F , Mantovani A. Inflammation and cancer: back to Virchow? Lancet . 2001 ; 357 : 539 - 45 .
23. Elinav E , Nowarski R , Thaiss CA , Hu B , Jin C , Flavell RA . Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms . Nat Rev Cancer . 2013 ; 13 : 759 - 71 .
24. McKeown DJ , Brown DJF , Kelly A , Wallace AM , McMillan DC . The relationship between circulating concentrations of Creactive protein, inflammatory cytokines and cytokine receptors in patients with non-small-cell lung cancer . Br J Cancer . 2004 ; 91 : 1993 - 5 .
25. Miura T , Mitsunaga S , Ikeda M , Shimizu S , Ohno I , Takahashi H , et al. Characterization of patients with advanced pancreatic cancer and high serum interleukin-6 levels . Pancreas. 2015 ; 44 : 756 - 63 .
26. Szkandera J , Stotz M , Absenger G , Stojakovic T , Samonigg H , Kornprat P , et al. Validation of C-reactive protein levels as a prognostic indicator for survival in a large cohort of pancreatic cancer patients . Br J Cancer . 2014 ; 110 : 183 - 8 .
27. Pine JK , Fusai KG , Young R , Sharma D , Davidson BR , Menon KV , et al. Serum C-reactive protein concentration and the prognosis of ductal adenocarcinoma of the head of pancreas . Eur J Surg Oncol . 2009 ; 35 : 605 - 10 .
28. Kishi T , Nakamura A , Itasaka S , Shibuya K , Matsumoto S , Kanai M , et al. Pretreatment C-reactive protein level predicts outcome and patterns of failure after chemoradiotherapy for locally advanced pancreatic cancer . Pancreatology . 2015 ; 15 : 694 - 700 .
29. Kowalski-Saunders PW , Winwood PJ , Arthur MJ , Wright R. Reversible inhibition of albumin production by rat hepatocytes maintained on a laminin-rich gel (Engelbreth-Holm-Swarm) in response to secretory products of Kupffer cells and cytokines . Hepatology . 1992 ; 16 : 733 - 41 .
30. Barber MD , Ross JA , Fearon KC . Changes in nutritional, functional, and inflammatory markers in advanced pancreatic cancer . Nutr Cancer . 1999 ; 35 : 106 - 10 .
31. Fanali G , di Masi A , Trezza V , Marino M , Fasano M , Ascenzi P. Human serum albumin: from bench to bedside . Mol Asp Med . 2012 ; 33 : 209 - 90 .
32. Nazha B , Moussaly E , Zaarour M , Weerasinghe C , Azab B. Hypoalbuminemia in colorectal cancer prognosis: nutritional marker or inflammatory surrogate ? World J Gastrointest Surg . 2015 ; 7 : 370 - 7 .
33. Boonpipattanapong T , Chewatanakornkul S. Preoperative carcinoembryonic antigen and albumin in predicting survival in patients with colon and rectal carcinomas . J Clin Gastroenterol . 2006 ; 40 : 592 - 5 .
34. Siddiqui A , Heinzerling J , Livingston EH , Huerta S. Predictors of early mortality in veteran patients with pancreatic cancer . Am J Surg . 2007 ; 194 : 362 - 6 .
35. Onate-Ocana LF , Aiello-Crocifoglio V , Gallardo-Rincon D , Herrera-Goepfert R , Brom-Valladares R , Carrillo JF , et al. Serum albumin as a significant prognostic factor for patients with gastric carcinoma . Ann Surg Oncol . 2007 ; 14 : 381 - 9 .