C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer

  • Authors:
    • Minjie Mao
    • Xiaoli Wei
    • Hui Sheng
    • Peidong Chi
    • Yijun Liu
    • Xiaoyan Huang
    • Yifan Xiang
    • Qianying Zhu
    • Shan Xing
    • Wanli Liu
  • View Affiliations

  • Published online on: October 13, 2017     https://doi.org/10.3892/ol.2017.7179
  • Pages:7417-7424
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Multiple studies have reported the prognostic association of certain inflammatory factors with various types of cancer. The present study assessed the prognostic value of the C‑reactive protein (CRP)/albumin (Alb) ratio and the neutrophil/lymphocyte ratio (NLR), separately and in combination, in gastric cancer (GC). A total of 337 cases pathologically diagnosed with gastric adenocarcinoma were retrospectively evaluated. The clinicopathological and prognostic relevance of the CRP/Alb ratio and NLR and their combination were analyzed. The optimal cut‑off values of the CRP/Alb ratio and NLR were 0.38 and 3.14, respectively. High CRP/Alb ratio (≥0.38) and NLR (≥3.14) values were associated with increased tumor invasion, more distant metastasis and a more advanced tumor‑node‑metastasis stage (all P<0.05). In addition, a high NLR value was also associated with increased tumor size (P=0.02). The CRP/Alb ratio (≥0.38/<0.38) and NLR (≥3.14/<3.14) were independent prognostic factors for overall survival time (OS) in GC by multivariate analysis (P=0.005 and P=0.001). Using the CRP/Alb ratio and NLR classification, patients were stratified into three subgroups with different OS time (P<0.001), which were identified as independent prognostic variables in multivariate analysis (P<0.001). The present study demonstrated that the CRP/Alb ratio and NLR were independent prognostic factors for OS in patients with GC. The combination of these indexes was associated with significant prognostic value and may further stratify prognosis.

Introduction

Gastric cancer (GC) is one of the most common types of tumor globally. In 2015, GC had the second highest incidence and rate of mortality among cancer patients in China (1). Due to the rapid progression of GC and the absence of early specific symptoms and signs, the majority of patients are diagnosed at the late stage of gastric carcinoma (25). At present, surgery is the preferred treatment for patients without distant metastasis, and postoperative metastasis and recurrence are the predominant causes of mortality (3,5). Although disease-free and overall survival (OS) may be improved by postoperative chemotherapy and radiotherapy, the prognosis of GC remains poor (3,6). Identifying simple but effective prognostic markers for GC remains an important aim for researchers.

Inflammation occurs in various types of tumor, and serves a crucial function in tumor development and distant metastasis (710). Previous studies have indicated that inflammation is associated with the formation of the tumor microenvironment by inflammatory mediators, including vasoactive amines and cytokines (1113). The C-reactive protein (CRP)/albumin (Alb) ratio is used as a novel inflammation-based prognostic indicator in multiple types of tumor. Previous studies have demonstrated the prognostic value of CRP/Alb ratio in colorectal (14) and esophageal cancer (15), hepatocellular carcinoma (16), and renal (17) and pancreatic cancer (18). Another important inflammatory marker is the neutrophil/lymphocyte ratio (NLR). NLR represents the balance between inflammatory activation and regulatory factors (19). Increased NLR may also serve as an independent prognostic risk factor in multiple types of cancer, including lung (20) and breast cancer (21), renal cell carcinoma (22), and ovarian cancer (23). The present study evaluated the individual and combined prognostic value of CRP/Alb and NLR in Chinese patients with GC.

Patients and methods

Patients

The present study retrospectively reviewed the clinical data of 395 patients pathologically diagnosed with GC from Sun Yat-sen University Cancer Center between January 2010 and December 2010 (Guangzhou, China). The patients were classified and staged based on the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system (24). Patients without pathological diagnosis and laboratory test information on CRP, Alb, neutrophils and lymphocytes were excluded from analysis. The present study also excluded patients with other tumors, autoimmune diseases and those lost to follow-up. In total, 337 of the 395 patients reviewed were included for analysis in the present study. Of these, 237 (70.3%) were male and 100 (29.7%) were female (median age, 59; age range, 19–89). The information on CRP, Alb, neutrophils and lymphocytes was obtained from the test report from the Department of Clinical Laboratory at the Sun Yat-sen University Cancer Center. Other clinicopathological characteristics were collected through medical records.

Ethics statement

All patients provided written informed consent for the information to be used in the database of Sun Yat-sen University Cancer Center. The Ethics Committee at the Sun Yat-sen University Cancer Center approved the present study. The present study was conducted in accordance with the ethical standards of the World Medical Association Declaration of Helsinki.

Statistical analysis

Data are expressed as the mean ± standard deviation. The significance of association between the CRP/Alb ratio or NLR, and the clinicopathological characteristics were assessed using the χ2 test. OS was defined as the time interval between diagnosis and mortality due to GC or the last follow-up. The optimal cut-off points for continuous prognostic indices were determined using the method reported by Budczies et al (25). Survival curves were constructed using the Kaplan-Meier method. Differences in survival were assessed using the log-rank test. The Cox proportional hazards regression model was used for univariate and multivariate analysis. The significant prognostic factors identified in univariate analysis were selected for multivariate analysis. All statistical analyses were performed using SPSS 13.0 (SPSS, Inc., Chicago, IL, USA). A two-tailed P<0.05 was considered to indicate a statistically significant difference.

Results

Patient characteristics

A total of 337 patients were included for analysis in the present study; however, some of the patients' data of tumor size, location and differentiation level were lost. Of the available data, 42 (12.5%), 49 (14.5%), 142 (42.1%) and 104 (30.9%) were staged I, II, III and IV, respectively. In addition, 89 (34.1%) patients had tumors <4 cm, and 172 (65.9%) had primary tumors ≥4 cm. The present study identified that 185 (55.2%) and 104 (31.1%) patients with tumors located in the proximal and distal stomach, respectively, while 46 (13.7%) exhibited tumors in other locations, including gastric stump cancer and linitis plastica. A total of 230 (70.1%) patients exhibited poorly or not differentiated tumors, 96 (29.3%) exhibited moderately differentiated tumors, and only 2 (0.6%) patients exhibited well-differentiated tumors.

Association between CRP/Alb ratio, NLR and clinicopathological characteristics

The association between CRP/Alb ratio and NLR, and clinicopathological characteristics was assessed (Table I). The CRP/Alb ratio ranged from 0.003–4.77 (median, 0.23), and NLR ranged from 0.47–23.00 (median, 2.95). For OS, the optimal cut-off values of the CRP/Alb ratio and NLR were 0.38 and 3.41, respectively. The present study revealed that high CRP/Alb ratio and NLR values were associated with increased tumor invasion (CRP/Alb, P=0.006; NLR, P=0.005), increased distant metastasis (CRP/Alb, P<0.001; NLR, P<0.001) and a more advanced TNM stage (CRP/Alb, P<0.001; NLR, P<0.001). In addition, a high NLR value was associated with increased tumor size (P=0.02).

Table I.

Association between the CRP/ALB ratio and NLR with clinicopathological characteristics in patients with gastric cancer.

Table I.

Association between the CRP/ALB ratio and NLR with clinicopathological characteristics in patients with gastric cancer.

CRP/ALB ratioNLR


Characteristic<0.3778 n, (%)≥0.3778 n, (%)P-value<3.41 n, (%)≥3.41 n, (%)P-value
Sex 0.280 0.130
  Male195 (69.1)42 (76.4) 176 (68.2)61 (77.2)
  Female87 (30.9)13 (23.6) 82 (31.8)18 (22.8)
Age, years 0.290 0.180
  ≤59140 (49.6)23 (41.8) 130 (50.4)33 (41.8)
  >59142 (50.4)32 (58.2) 128 (49.6)46 (58.2)
TNM stageb <0.001a <0.001a
  I40 (14.2)2 (3.6) 40 (15.5)2 (2.5)
  II45 (16.0)4 (7.3) 42 (16.3)7 (8.9)
  III126 (44.7)16 (29.1) 117 (45.3)25 (31.6)
  IV71 (25.2)33 (60.0) 59 (22.9)45 (57.0)
N stageb 0.600 0.180
  N072 (30.1)6 (25.0) 70 (31.3)8 (20.5)
  N1+N2+N3167 (69.9)18 (75.0) 154 (68.8)31 (79.5)
T stageb 0.006a 0.005a
  T1+T2+T380 (32.8)2 (7.4) 77 (33.6)5 (11.9)
  T4164 (67.2)25 (92.6) 152 (66.4)37 (88.1)
M stageb <0.001a <0.001a
  M0211 (74.8)22 (40.0) 199 (77.1)34 (43.0)
  M171 (25.2)33 (60.0) 59 (22.4)45 (57.0)
Primary tumor size, cm 0.320 0.021a
  <4.083 (35.0)6 (25.0) 82 (36.9)7 (17.9)
  ≥4.0154 (65.0)18 (75.0) 140 (63.1)32 (82.1)
Tumor location 0.230 0.070
  Proximal160 (57.1)25 (45.5) 146 (56.8)39 (50.0)
  Remote84 (30.0)20 (36.4) 82 (31.9)22 (28.2)
  Other36 (12.9)10 (18.2) 29 (11.3)17 (21.8)
Degree of differentiation 0.590 0.390
  Poorly/not differentiated195 (70.9)35 (66.0) 177 (69.4)53 (72.6)
  Moderately differentiated78 (28.4)18 (34.0) 77 (30.2)19 (26.0)
  Well-differentiated2 (0.7)0 (0.0) 1 (0.4)1 (1.4)

a Statistically significant P-value.

b AJCC. CRP, C-reactive protein; ALB, albumin; n, number of patients; TNM, tumor-node-metastasis; AJCC, American Joint Committee on Cancer.

Prognostic value of the CRP/Alb ratio, NLR and OS

The median survival time for the patients was 29.77 months (range, 0.43–59.57 months). Survival analysis revealed that patients with a high CRP/Alb ratio were associated with a significantly decreased OS rate compared with those with a decreased CRP/Alb ratio (P<0.001; Fig. 1). Similarly, patients with a high NLR value were associated with a significantly decreased OS rate compared with those with a low NLR (P<0.001; Fig. 2). In univariate analysis, age (P=0.005), tumor location (P<0.001), TNM stage (P<0.001), distant metastasis (P<0.001), surgery (P<0.001), CRP/Alb ratio (P<0.001) and NLR (P<0.001) were revealed to be significantly associated with OS. Multivariate analysis identified age (P<0.001), TNM stage (P<0.001), surgery (P=0.002), CRP/Alb ratio (P=0.005) and NLR (P=0.001) as independent prognostic factors (Table II).

Table II.

Prognostic value of the CRP/ALB ratio and NLR for overall survival in patients with gastric cancer by univariate and multivariate analysis.

Table II.

Prognostic value of the CRP/ALB ratio and NLR for overall survival in patients with gastric cancer by univariate and multivariate analysis.

Univariate analysisMultivariate analysis


CharacteristicN, (%)P-valueHazard ratio95% CIP-value
Sex 0.500
  Male237 (70.3)
  Female100 (29.7)
Age, years 0.005a <0.001a
  ≤59163 (48.4) 1.00Reference
  >59174 (51.6) 1.921.39–2.65
Tumor location <0.001a
  Proximal185 (55.2)
  Remote104 (31.0)
  Other46 (13.7)
Degree of differentiation 0.060
  Poorly or not differentiated230 (70.1)
  Moderately differentiated96 (29.3)
  Well-differentiated2 (0.6)
TNM stageb <0.001a <0.001a
  I42 (12.5) 1.00Reference
  II49 (14.5) 1.430.55–3.690.470
  III142 (42.1) 4.241.95–9.22 <0.001a
  IV104 (30.9) 8.173.53–18.91 <0.001a
Distant metastasis <0.001a
  No233 (69.1)
  Yes104 (30.9)
Surgery <0.001a 0.002a
  No74 (22.0) 1.00Reference
  Yes263 (78.0) 0.460.28–0.75
CRP/ALB ratio <0.001a 0.005a
  <0.3778282 (83.7) 1.00Reference
  ≥0.377855 (16.3) 1.781.20–2.65
NLR <0.001a 0.001a
  <3.41258 (76.6) 1.00Reference
  ≥3.4179 (23.4) 1.741.25–2.44

a Statistically significant prognostic factor identified using univariate or multivariate analysis.

b AJCC. The cut-off points for age, the CRP/ALB ratio, and NLR were determined using the method reported by Budczies et al (25). TNM, tumor-node-metastasis; AJCC, American Joint Committee on Cancer; CI, confidence interval; CRP, C-reactive protein; ALB, albumin; NLR, neutrophil/lymphocyte ratio.

Prognostic value of the CRP/Alb ratio and NLR classification

According to the optimal cut-off values of the CRP/Alb ratio (<0.38/≥0.38) and NLR (<3.41/≥3.41), the present study classified the patients into subgroups: Group I, patients with increased CRP/Alb ratio (≥0.38) and NLR (≥3.14); group III, patients with decreased CRP/Alb ratio (<0.38) and NLR (<3.14); and group II, all remaining patients. Among the 337 patients, 29 (8.60%) patients were located in group I, 76 (22.55%) patients were located in group II and 232 (68.84%) patients were located in group III. The median OS values for patients in group I, II and III were 5.10, 17.80, and 46.50 months, respectively. Using univariate analysis, the present study identified that patients in group I exhibited the lowest OS of the subgroups (P<0.001). Patients in group II [hazard ratio (HR), 95%; confidence interval (CI), 0.33 (0.19–0.57); P<0.001] and group III [HR, 95%; CI, 0.25 (0.15–0.42); P<0.001] exhibited significantly increased OS compared with patients in group I (Fig. 3; Table III). Univariate analysis revealed that age (P=0.005), tumor location (P<0.001), TNM stage (P<0.001), distant metastasis (P<0.001), surgery (P<0.001), and CRP/Alb ratio and NLR classification (P<0.001) were significant prognostic factors. Multivariate analysis also demonstrated that these parameters, with the exception of tumor location, were significant prognostic factors. Notably, the CRP/Alb ratio and NLR classification (P<0.001) was identified as an independent prognostic factor in univariate and multivariate analyses (Table III).

Table III.

Prognostic value of the CRP/ALB ratio and NLR for overall survival in patients with gastric cancer by univariate and multivariate analysis.

Table III.

Prognostic value of the CRP/ALB ratio and NLR for overall survival in patients with gastric cancer by univariate and multivariate analysis.

Univariate analysisMultivariate analysis


CharacteristicN, (%)P-valueHazard ratio95% confidence intervalP-value
Sex 0.500
  Male237 (70.3)
  Female100 (29.3)
Age, years 0.005a <0.001
  ≤59163 (48.4) 1.00Reference
  >59174 (51.6) 2.011.45–2.78
Tumor location <0.001a
  Proximal185 (55.2)
  Remote104 (31.0)
  Other46 (13.7)
Degree of differentiation 0.060
  Poorly or not differentiated230 (70.1)
  Moderately differentiated96 (29.3)
  Well-differentiated2 (0.6)
TNM stageb <0.001a <0.001a
  I42 (12.5) 1.00Reference
  II49 (14.5) 1.400.54–3.610.500
  III142 (42.1) 4.382.01–9.51 <0.001a
  IV104 (30.9) 8.503.68–19.63 <0.001a
Distant metastasis <0.001a
  No233 (69.1)
  Yes104 (30.9)
Surgery <0.001a <0.001a
  No74 (22.0) 1.00Reference
  Yes263 (78.0) 0.490.30–0.80
CRP/ALB ratio and NLR classification <0.001a <0.001a
  Group I29 (8.6) 1.00Reference
  Group II76 (22.6) 0.330.19–0.57 <0.001a
  Group III232 (68.8) 0.250.15–0.42 <0.001a

a Statistically significant prognostic factor identified using univariate or multivariate analysis.

b AJCC. Group I, patients with increased CRP/ALB ratio (>0.3778) and NLR (>3.14); group III, patients with decreased CRP/ALB ratio (≤0.3778) and NLR (≤3.14); group II, all remaining patients. CRP, C-reactive protein; ALB, albumin; NLR, neutrophil/lymphocyte ratio; TNM, tumor-node-metastasis; AJCC, American Joint Committee on Cancer.

Discussion

GC is a common malignant tumor of the upper digestive tract. In 2015, GC exhibited the second highest incidence and mortality rate among various types of cancer in China (1). In previous studies, plasma fibrinogen (26), α-fetoprotein (27), carcinoembryonic antigen-related cell adhesion molecule 5 (28) and the platelet/lymphocyte ratio (29) were demonstrated to be prognostic indicators for GC with the same TNM stage. The levels of CRP, Alb, neutrophils and lymphocytes are all routinely tested in clinical practice, which means that data on these parameters are readily available. The present study revealed that CRP/Alb ratio and NLR served as independent prognostic factors for OS in patients with GC. The combination of these indexes was associated with significant prognostic value and may further stratify prognosis.

The association between inflammation and cancer is complex. During the inflammatory response, cytokines [e.g., interleukin (IL)-6] and chemokines (e.g., C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 8) are produced, which may activate signal transducer and activator of transcription 3 and nuclear factor κB, and recruit an increased number of inflammatory cells, including neutrophilic granulocytes and mononuclear macrophages, to the lesion site and thereby assist in forming an inflammatory microenvironment (13,30,31). The interaction between tumor cells and inflammatory factors may suppress the immunosurveillance of T and natural killer cells (32), enhance the permeability of blood and lymphatic vessels and degrade the extracellular matrix, thereby potentiating tumor development and metastasis (12,33). Furthermore, tumor cells may secrete inflammatory mediators and thereby assist in forming an inflammatory microenvironment (34).

CRP and Alb are produced by liver cells. CRP is an acute phase protein regulated by IL-6, tumor necrosis factor and other inflammatory factors (35). Therefore, CRP may indicate inflammation. Previous studies have demonstrated that an increased level of CRP may be associated with poorer prognosis in patients with tumors, including ovarian cancer, penile cancer and non-small cell lung cancer (3638). In addition, malabsorption and malnutrition may be associated with decreased survival time in various tumors, including esophageal squamous cell carcinomas and endometrial cancer (39,40). In a previous study, Alb was used to estimate nutritional status. For patients with GC, protein digestion and absorption were decreased, whereas protein metabolism was increased, resulting in a negative nitrogen balance (18,39). The CRP/Alb ratio is a useful prognostic indicator that was initially used to identify patients with serious conditions on an acute medical ward by Fairclough et al (41). Subsequently, multiple studies have demonstrated that the CRP/Alb ratio exhibited prognostic value in numerous types of cancer (1518,42). The present study revealed that a high CRP/Alb ratio indicated increased tumor invasion and metastasis and poorer prognosis compared with a low CRP/Alb ratio.

NLR serves as an index in routine blood tests. Multiple studies have confirmed that NLR is an easily available and reliable marker, which is associated with poor prognosis in various malignancies (1923). The present study revealed that NLR was significantly associated with TNM stage, tumor invasion, tumor size, distant metastasis and poor prognosis, which was consistent with a previous study (43). The balance between the inflammatory and immune response is also reflected by NLR. Neutrophils contribute to inflammation by activating pro-angiogenic factors, including vascular endothelial growth factor or inflammatory cytokines (e.g., IL-1β) (44,45). In addition, these neutrophils may also secrete agents that promote tumor cellular proliferation, angiogenesis, invasion and metastasis (46), and they may inhibit T cells (47). As important components of the non-specific and adaptive immune response, lymphocytes are able to destroy tumor cells via cytotoxic cells and cytokine secretion (48). A decreased lymphocyte count results in reduced tumor resistance (49). These mechanisms support the results of the present study.

The multivariate analysis of the present study demonstrated that the CRP/Alb ratio and NLR exhibited significant prognostic value in GC. In the present study, the patients were classified according to CRP/Alb ratio (<0.38/≥0.38) and NLR (<3.41/v3.41). In groups I, II, and III, the median OS was 5.10, 17.80 and 46.50 months, respectively. The survival difference among the subgroups may be due to the CRP/Alb ratio and NLR, which reflect a combination of inflammation, immune and nutrition status caused by tumor progression Therefore, the combination of the CRP/Alb ratio and NLR was associated with significant prognostic value in GC.

Although the prognostic value of the CRP/Alb ratio and NLR in GC has been reported previously (42,50), to the best of our knowledge, the present study is the first to report that the that the combination of the CRP/Alb ratio and NLR is associated with significant prognostic value and may further stratify prognosis compared with using single indicators.

However, the present study has a number of limitations. The present study was a retrospective analysis, and the conclusions require confirmation by perspective studies. Secondly, the present study did not use a uniform cut-off value for the CRP/Alb ratio and NLR. Therefore, different statistical methods may obtain different thresholds. However, the method used by the present study was based on R, which has been reliably used by other studies (15,51,52). To conclude, the present study revealed that the combination of the CRP/Alb ratio and NLR represents a potential inflammation-based prognostic marker. This marker was associated with invasive clinicopathological characteristics and was able to predict prognosis in patients with GC. Larger, prospective studies are required to evaluate the results of the present study in the context of other types of malignancy.

Acknowledgements

The authors would like to thank the staff of the Biochemical Laboratory of the Department of Clinical Laboratory of Sun Yat-sen University Cancer Center for providing biochemical markers.

Glossary

Abbreviations

Abbreviations:

GC

gastric cancer

OS

overall survival

TNM

tumor-node-metastasis

CRP/Alb ratio

C-reactive protein/albumin ratio

NLR

neutrophil/lymphocyte ratio

References

1 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Jass JR, Sobin LH and Watanabe H: The World Health Organization's histologic classification of gastrointestinal tumors. A commentary on the second edition. Cancer. 66:2162–2167. 1990. View Article : Google Scholar : PubMed/NCBI

3 

Waddell T, Verheij M, Allum W, Cunningham D, Cervantes A and Arnold D: European Society for Medical Oncology (ESMO); European Society of Surgical Oncology (ESSO); European Society of Radiotherapy and Oncology (ESTRO): Gastric cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Eur J Surg Oncol. 40:584–591. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Lauren P: The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 64:31–49. 1965. View Article : Google Scholar : PubMed/NCBI

5 

Tomasello G, Ghidini M, Liguigli W, Ratti M, Toppo L and Passalacqua R: Targeted therapies in gastric cancer treatment: Where we are and where we are going. Invest New Drugs. 34:378–393. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Roukos DH: Current status and future perspectives in gastric cancer management. Cancer Treat Rev. 26:243–255. 2000. View Article : Google Scholar : PubMed/NCBI

7 

Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Demaria S, Pikarsky E, Karin M, Coussens LM, Chen YC, El-Omar EM, Trinchieri G, Dubinett SM, Mao JT, Szabo E, et al: Cancer and inflammation: Promise for biologic therapy. J Immunother. 33:335–351. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Mantovani A, Allavena P, Sica A and Balkwill F: Cancer-related inflammation. Nature. 454:436–444. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Solinas G, Germano G, Mantovani A and Allavena P: Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 86:1065–1073. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Lou Y, Diao L, Cuentas ER, Denning WL, Chen L, Fan YH, Byers LA, Wang J, Papadimitrakopoulou VA, Behrens C, et al: Epithelial-mesenchymal transition is associated with a distinct tumor microenvironment including elevation of inflammatory signals and multiple immune checkpoints in lung adenocarcinoma. Clin Cancer Res. 22:3630–3642. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Markowitz GJ, Michelotti GA, Diehl AM and Wang XF: Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma. Sci Bull (Beijing). 60:762–772. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Sanguinetti A, Santini D, Bonafè M, Taffurelli M and Avenia N: Interleukin-6 and pro inflammatory status in the breast tumor microenvironment. World J Surg Oncol. 13:1292015. View Article : Google Scholar : PubMed/NCBI

14 

Ishizuka M, Nagata H, Takagi K, Iwasaki Y, Shibuya N and Kubota K: Clinical significance of the C-reactive protein to albumin ratio for survival after surgery for colorectal cancer. Ann Surg Oncol. 23:900–907. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Wei XL, Wang FH, Zhang DS, Qiu MZ, Ren C, Jin Y, Zhou YX, Wang DS, He MM, Bai L, et al: A novel inflammation-based prognostic score in esophageal squamous cell carcinoma: The C-reactive protein/albumin ratio. BMC Cancer. 15:3502015. View Article : Google Scholar : PubMed/NCBI

16 

Kinoshita A, Onoda H, Imai N, Iwaku A, Oishi M, Tanaka K, Fushiya N, Koike K, Nishino H and Matsushima M: The C-reactive protein/albumin ratio, a novel inflammation-based prognostic score, predicts outcomes in patients with hepatocellular carcinoma. Ann Surg Oncol. 22:803–810. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Chen Z, Shao Y, Fan M, Zhuang Q, Wang K, Cao W, Xu X and He X: Prognostic significance of preoperative C-reactive protein: Albumin ratio in patients with clear cell renal cell carcinoma. Int J Clin Exp Pathol. 8:14893–14900. 2015.PubMed/NCBI

18 

Haruki K, Shiba H, Shirai Y, Horiuchi T, Iwase R, Fujiwara Y, Furukawa K, Misawa T and Yanaga K: The C-reactive protein to albumin ratio predicts long-term outcomes in patients with pancreatic cancer after pancreatic resection. World J Surg. 40:2254–2260. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Kim HS and Ku JH: Systemic inflammatory response based on neutrophil-to-lymphocyte ratio as a prognostic marker in bladder cancer. Dis Markers. 2016:83452862016. View Article : Google Scholar : PubMed/NCBI

20 

Wu G, Yao Y, Bai C, Zeng J, Shi D, Gu X, Shi X and Song Y: Combination of platelet to lymphocyte ratio and neutrophil to lymphocyte ratio is a useful prognostic factor in advanced non-small cell lung cancer patients. Thorac Cancer. 6:275–287. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Pistelli M, De Lisa M, Ballatore Z, Caramanti M, Pagliacci A, Battelli N, Ridolfi F, Santoni M, Maccaroni E, Bracci R, et al: Pre-treatment neutrophil to lymphocyte ratio may be a useful tool in predicting survival in early triple negative breast cancer patients. BMC Cancer. 15:1952015. View Article : Google Scholar : PubMed/NCBI

22 

Bazzi WM, Tin AL, Sjoberg DD, Bernstein M and Russo P: The prognostic utility of preoperative neutrophil-to-lymphocyte ratio in localized clear cell renal cell carcinoma. Can J Urol. 23:8151–8154. 2016.PubMed/NCBI

23 

Williams KA, Labidi-Galy SI, Terry KL, Vitonis AF, Welch WR, Goodman A and Cramer DW: Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer. Gynecol Oncol. 132:542–550. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Mao MJ, Wei XL, Sheng H, Wang XP, Li XH, Liu YJ, Xing S, Huang Q, Dai SQ and Liu WL: Clinical significance of preoperative albumin and globulin ratio in patients with gastric cancer undergoing treatment. Biomed Res Int. 2017:30832672017. View Article : Google Scholar : PubMed/NCBI

25 

Budczies J, Klauschen F, Sinn BV, Győrffy B, Schmitt WD, Darb-Esfahani S and Denkert C: Cutoff Finder: A comprehensive and straightforward Web application enabling rapid biomarker cutoff optimization. PLoS One. 7:e518622012. View Article : Google Scholar : PubMed/NCBI

26 

Yamamoto M, Kurokawa Y, Miyazaki Y, Makino T, Takahashi T, Yamasaki M, Nakajima K, Takiguchi S, Mori M and Doki Y: Usefulness of preoperative plasma fibrinogen versus other prognostic markers for predicting gastric cancer recurrence. World J Surg. 40:1904–1909. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Chen Y, Qu H, Jian M, Sun G and He Q: High level of serum AFP is an independent negative prognostic factor in gastric cancer. Int J Biol Markers. 30:e387–393. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Deng K, Yang L, Hu B, Wu H, Zhu H and Tang C: The prognostic significance of pretreatment serum CEA levels in gastric cancer: A meta-analysis including 14651 patients. PLoS One. 10:e1241512015.

29 

Li S, Xu X, Liang D, Tian G, Song S and He Y: Prognostic value of blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with gastric cancer. Zhonghua Zhong Liu Za Zhi. 36:910–915. 2014.(In Chinese). PubMed/NCBI

30 

Mohamed MM, El-Ghonaimy EA, Nouh MA, Schneider RJ, Sloane BF and El-Shinawi M: Cytokines secreted by macrophages isolated from tumor microenvironment of inflammatory breast cancer patients possess chemotactic properties. Int J Biochem Cell Biol. 46:138–147. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Ye Y, Liu S, Wu C and Sun Z: TGFβ modulates inflammatory cytokines and growth factors to create premetastatic microenvironment and stimulate lung metastasis. J Mol Histol. 46:365–375. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Liu Y and Cao X: Immunosuppressive cells in tumor immune escape and metastasis. J Mol Med (Berl). 94:509–522. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Quail DF and Joyce JA: Microenvironmental regulation of tumor progression and metastasis. Nat Med. 19:1423–1437. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Grivennikov SI, Greten FR and Karin M: Immunity, inflammation, and cancer. Cell. 140:883–899. 2010. View Article : Google Scholar : PubMed/NCBI

35 

Mocellin MC, Pastore e Silva Jde A, Camargo Cde Q, Fabre ME, Gevaerd S, Naliwaiko K, Moreno YM, Nunes EA and Trindade EB: Fish oil decreases C-reactive protein/albumin ratio improving nutritional prognosis and plasma fatty acid profile in colorectal cancer patients. Lipids. 48:879–888. 2013. View Article : Google Scholar : PubMed/NCBI

36 

Dobrzycka B, Mackowiak-Matejczyk B, Terlikowska KM, Kulesza-Bronczyk B, Kinalski M and Terlikowski SJ: Serum levels of IL-6, IL-8 and CRP as prognostic factors in epithelial ovarian cancer. Eur Cytokine Netw. 24:106–113. 2013.PubMed/NCBI

37 

Steffens S, Al Ghazal A, Steinestel J, Lehmann R, Wegener G, Schnoeller TJ, Cronauer MV, Jentzmik F, Schrader M, Kuczyk MA and Schrader AJ: High CRP values predict poor survival in patients with penile cancer. BMC Cancer. 13:2232013. View Article : Google Scholar : PubMed/NCBI

38 

Szturmowicz M, Rudziński P, Kacprzak A, Langfort R, Bestry I, Broniarek-Samson B and Orłowski T: Prognostic value of serum C-reactive protein (CRP) and cytokeratin 19 fragments (Cyfra 21-1) but not carcinoembryonic antigen (CEA) in surgically treated patients with non-small cell lung cancer. Pneumonol Alergol Pol. 82:422–429. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Heneghan HM, Zaborowski A, Fanning M, McHugh A, Doyle S, Moore J, Ravi N and Reynolds JV: Prospective study of malabsorption and malnutrition after esophageal and gastric cancer surgery. Ann Surg. 262:803–807. 2015. View Article : Google Scholar : PubMed/NCBI

40 

Ryan AM, Power DG, Daly L, Cushen SJ, NíBhuachalla Ē and Prado CM: Cancer-associated malnutrition, cachexia and sarcopenia: The skeleton in the hospital closet 40 years later. Proc Nutr Soc. 75:pp. 199–211. 2016, View Article : Google Scholar : PubMed/NCBI

41 

Fairclough E, Cairns E, Hamilton J and 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). 9:30–33. 2009. View Article : Google Scholar : PubMed/NCBI

42 

Liu X, Sun X, Liu J, Kong P, Chen S, Zhan Y and Xu D: Preoperative C-reactive protein/albumin ratio predicts prognosis of patients after curative resection for gastric cancer. Transl Oncol. 8:339–345. 2015. View Article : Google Scholar : PubMed/NCBI

43 

Duan H, Zhang X, Wang FX, Cai MY, Ma GW, Yang H, Fu JH, Tan ZH, Meng YQ, Fu XY, et al: Prognostic role of neutrophil-lymphocyte ratio in operable esophageal squamous cell carcinoma. World J Gastroenterol. 21:5591–5597. 2015. View Article : Google Scholar : PubMed/NCBI

44 

Croker BA, Lewis RS, Babon JJ, Mintern JD, Jenne DE, Metcalf D, Zhang JG, Cengia LH, O'Donnell JA and Roberts AW: Neutrophils require SHP1 to regulate IL-1β production and prevent inflammatory skin disease. J Immunol. 186:1131–1139. 2011. View Article : Google Scholar : PubMed/NCBI

45 

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:pp. 12493–12498. 2006, View Article : Google Scholar : PubMed/NCBI

46 

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. View Article : Google Scholar : PubMed/NCBI

47 

Hao S, Andersen M and Yu H: Detection of immune suppressive neutrophils in peripheral blood samples of cancer patients. Am J Blood Res. 3:239–245. 2013.PubMed/NCBI

48 

Shi F, Shi M, Zeng Z, Qi RZ, Liu ZW, Zhang JY, Yang YP, Tien P and Wang FS: PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer. 128:887–896. 2011. View Article : Google Scholar : PubMed/NCBI

49 

Liu S, Lachapelle J, Leung S, Gao D, Foulkes WD and Nielsen TO: CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Res. 14:R482012. View Article : Google Scholar : PubMed/NCBI

50 

Kim JH, Han DS, Bang HY, Kim PS and Lee KY: Preoperative neutrophil-to-lymphocyte ratio is a prognostic factor for overall survival in patients with gastric cancer. Ann Surg Treat Res. 89:81–86. 2015. View Article : Google Scholar : PubMed/NCBI

51 

Choi WJ, Cleghorn MC, Jiang H, Jackson TD, Okrainec A and Quereshy FA: Preoperative neutrophil-to-lymphocyte ratio is a better prognostic serum biomarker than platelet-to-lymphocyte ratio in patients undergoing resection for nonmetastatic colorectal cancer. Ann Surg Oncol 22 Suppl. 3:S603–613. 2015. View Article : Google Scholar

52 

Zhou P, Erfani S, Liu Z, Jia C, Chen Y, Xu B, Deng X, Alfáro JE, Chen L, Napier D, et al: CD151-α3β1 integrin complexes are prognostic markers of glioblastoma and cooperate with EGFR to drive tumor cell motility and invasion. Oncotarget. 6:29675–29693. 2015. View Article : Google Scholar : PubMed/NCBI

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December 2017
Volume 14 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
APA
Mao, M., Wei, X., Sheng, H., Chi, P., Liu, Y., Huang, X. ... Liu, W. (2017). C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer. Oncology Letters, 14, 7417-7424. https://doi.org/10.3892/ol.2017.7179
MLA
Mao, M., Wei, X., Sheng, H., Chi, P., Liu, Y., Huang, X., Xiang, Y., Zhu, Q., Xing, S., Liu, W."C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer". Oncology Letters 14.6 (2017): 7417-7424.
Chicago
Mao, M., Wei, X., Sheng, H., Chi, P., Liu, Y., Huang, X., Xiang, Y., Zhu, Q., Xing, S., Liu, W."C‑reactive protein/albumin and neutrophil/lymphocyte ratios and their combination predict overall survival in patients with gastric cancer". Oncology Letters 14, no. 6 (2017): 7417-7424. https://doi.org/10.3892/ol.2017.7179