Esophageal cancer (EC) is one of the prevalent cancers worldwide, whose incidences vary widely in different countries and regions, with approximately 53.8% and 51.9% of all ECs occurring and dying in China [
The inflammation and nutrition are associated with cancer prognosis [
It is commonly recognized that CRP and PALB are both cheap and simple serum biomarkers which could be conducted in daily clinical practices. However, to our knowledge, no study has assessed the prognostic role of CPR (CRP/PALB ratio) in ESCC patients so far. Thus, the aim of our study was initially to explore the prognostic role of CPR for predicting prognosis with the optimal cut-off value in resectable ESCC patients.
From January 2007 to December 2010 in the Department of Thoracic Oncological Surgery, a retrospective study involving 346 resectable ESCC patients was conducted, along with the confirmation of levels of serum CRP, ALB, and PALB one week before surgery. Patients who received preoperative treatment, such as chemotherapy and/or radiotherapy, those who suffered from any form of inflammatory diseases or infections (acute or chronic) or systemic diseases, and those diagnosed with distant metastases were excluded. Written informed consent for the collection of specimen and other medical information were obtained from all patients before surgery. The current study was approved by the Ethics Committees of Zhejiang Cancer Hospital (IRB Approval No. IRB-2018-130).
The standard esophagectomy includes the Ivor Lewis procedure (for patients with ESCC in the middle or lower third) and McKeown procedure (for patients with ESCC in the upper third) [
The main clinical characteristics, such as age, gender, tumor length and location, vessel invasion, differentiation, TNM stage, and serum CRP, ALB, and PALB, were collected in our medical records. The TNM stage in this study was in accordance with the 7th AJCC/UICC TNM staging system [
The X-tile program was performed to calculate the optimum cut-off points for CRP, ALB, PALB, CAR, and CPR [
There were 76 (22.0%) women and 270 (78.0%) men in all 346 patients. The mean values for CRP, ALB, PALB, CAR, and CPR were 8.55 ± 12.18 mg/L (range 0.10-107.34 mg/L), 40.3 ± 5.3 g/L (range 26.6-52.4 g/L), 260 ± 65 mg/L (range 126-426 mg/L), 0.22 ± 0.34 (range 0.002-2.670), and 0.0365 ± 0.0539 (range 0.0003-0.4993), respectively. The optimum cut-off points according to the X-tile program for CRP, ALB, PALB, CAR, and CPR were 10.5 mg/L, 40.5 g/L, 248 mg/L, 0.3, and 0.03, respectively (Figure
Patients then were divided into two groups (high and low group) for further analyses (CPR ≤0.03 and CPR >0.03). The clinicopathologic characters regarding CPR and other clinical characters were shown in Table
Comparison of baseline clinical characteristics based on CPR in ESCC.
Cases (n, %) | CPR | P-value | ||
---|---|---|---|---|
≤ 0.03 (n, %) | > 0.03 (n, %) | |||
Age (years) | 0.108 | |||
≤60 | 199 (57.5) | 120 (54.3) | 79 (63.2) | |
>60 | 147 (42.5) | 101 (45.7) | 46 (36.8) | |
Gender | 0.077 | |||
Female | 76 (22.0) | 42 (19.0) | 34 (27.2) | |
Male | 270 (78.0) | 179 (81.0) | 91 (72.8) | |
Tumor length (cm) | 0.242 | |||
≤ 3.0 | 96 (27.7) | 66 (29.9) | 30 (24.0) | |
> 3.0 | 250 (72.3) | 155 (70.1) | 95 (76.0) | |
Tumor location | 0.179 | |||
Upper | 18 (5.2) | 11 (5.0) | 7 (5.6) | |
Middle | 164 (47.4) | 97 (43.9) | 67 (53.6) | |
Lower | 164 (47.4) | 113 (51.1) | 51 (40.8) | |
Vessel invasion | 0.025 | |||
Negative | 289 (83.5) | 192 (86.9) | 97 (77.6) | |
Positive | 57 (16.5) | 29 (13.1) | 28 (22.4) | |
Differentiation | 0.750 | |||
Well | 47 (13.6) | 32 (14.5) | 15 (12.0) | |
Moderate | 230 (66.5) | 144 (65.2) | 86 (68.8) | |
Poor | 69 (19.9) | 45 (20.3) | 24 (19.2) | |
TNM stage | 0.035 | |||
I | 88 (25.4) | 65 (29.4) | 23 (18.4) | |
II | 116 (33.5) | 75 (33.9) | 41 (32.8) | |
III | 142 (41.1) | 81 (36.7) | 61 (48.8) | |
CRP (mg/L) | <0.001 | |||
≤ 10.5 | 250 (72.3) | 219 (99.1) | 31 (24.8) | |
> 10.5 | 96 (27.7) | 2 (0.9) | 94 (75.2) | |
ALB (g/L) | 0.037 | |||
≤ 40.5 | 179 (51.7) | 105 (47.5) | 74 (59.2) | |
> 40.5 | 167 (48.3) | 116 (52.5) | 51 (40.8) | |
PALB (mg/L) | <0.001 | |||
≤ 248 | 161 (46.5) | 81 (36.7) | 80 (64.0) | |
> 248 | 185 (53.5) | 140 (63.3) | 45 (36.0) | |
CAR | <0.001 | |||
≤ 0.3 | 272 (78.6) | 221 (100) | 51 (40.8) | |
> 0.3 | 74 (21.4) | 0 (0) | 74 (59.2) |
ESCC: esophageal squamous cell carcinoma; CRP: C-reactive protein; PALB: prealbumin; ALB: albumin; CPR: C-reactive protein to prealbumin ratio; CAR: C-reactive protein to albumin ratio; TNM: tumor, node, metastasis.
The mean values grouped by TNM stage for CPR were 0.0278 ± 0.0421, 0.0343 ± 0.0398, and 0.0437 ± 0.0680, respectively, with significant differences between TNM I and TNM III (
Significant differences were found between TNM I and TNM III (P=0.030) (a). Negative correlations between CRP and ALB (b) and CRP and PALB (c), respectively, and positive correlations between ALB and PALB (d) were found.
Patients with a high level of CPR (>0.03) were associated with poor CSS (
It is generally recognized that several factors, such as tumor length, vessel invasion, CRP, ALB, PALB, CAR, CPR, and TNM stage, were significantly associated with CSS in univariate analyses (Table
Univariate and multivariate analyses of CSS in ESCC patients.
Univariate analysis | P-value | Multivariate analysis | P-value | |
---|---|---|---|---|
HR (95% CI) | HR (95% CI) | |||
Age (years) | 0.584 | |||
≤ 60 | 1.000 | |||
> 60 | 0.930 (0.717-1.206) | |||
Gender | 0.530 | |||
Female | 1.000 | |||
Male | 1.105 (0.809-1.510) | |||
Tumor length (cm) | 0.001 | |||
≤ 3.0 | 1.000 | |||
> 3.0 | 1.634 (1.208-2.211) | |||
Tumor location | 0.845 | |||
Upper | 1.000 | |||
Middle | 1.160 (0.624-2.156) | 0.638 | ||
Lower | 1.197 (0.644-2.222) | 0.569 | ||
Vessel invasion | 0.003 | |||
Negative | 1.000 | |||
Positive | 1.636 (1.187-2.255) | |||
Differentiation | 0.075 | |||
Well | 1.000 | |||
Moderate | 1.247 (0.834-1.864) | 0.282 | ||
Poor | 1.660 (1.045-2.638) | 0.032 | ||
CRP (mg/L) | <0.001 | |||
≤ 10.5 | 1.000 | |||
> 10.5 | 1.896 (1.450-2.479) | |||
ALB (g/L) | 0.002 | |||
≤ 40.5 | 1.000 | |||
> 40.5 | 0.669 (0.517-0.867) | |||
PALB (mg/L) | <0.001 | |||
≤ 248 | 1.000 | |||
> 248 | 0.613 (0.474-0.792) | |||
CPR | <0.001 | 0.008 | ||
≤ 0.03 | 1.000 | 1.000 | ||
> 0.03 | 2.116 (1.634-2.739) | 1.630 (1.135-2.342) | ||
CAR | <0.001 | 0.052 | ||
≤ 0.3 | 1.000 | |||
> 0.3 | 1.485 (0.997-2.212) | |||
Adjuvant therapy | 1.000 | 0.329 | ||
No | 1.149 (0.870-1.517) | |||
Yes | ||||
TNM stage | <0.001 | <0.001 | ||
I | 1.000 | 1.000 | ||
II | 1.804 (1.237-2.631) | 0.002 | 1.628 (1.111-2.387) | 0.012 |
III | 3.067 (2.150-4.373) | <0.001 | 2.559 (1.786-3.667) | <0.001 |
BMI (kg/m2) | ||||
≥ 20 | 1.000 | <0.001 | 1.000 | <0.001 |
< 20 | 2.006 (1.551-2.595) | 1.877 (1.444-2.440) |
ESCC: esophageal squamous cell carcinoma; CRP: C-reactive protein; PALB: prealbumin; ALB: albumin; CPR: C-reactive protein to prealbumin ratio; CAR: C-reactive protein to albumin ratio; TNM: tumor, node, metastasis; BMI: body mass index; CI: confidence interval; HR: hazard ratio.
Multivariate analyses of OS in patients with ESCC.
HR (95% CI) | P-value | |
---|---|---|
TNM stage | ||
II vs. I | 1.518 (1.048-2.199) | 0.027 |
III vs. I | 2.386 (1.685-3.379) | <0.001 |
BMI (kg/m2) (≤ 20 vs. > 20) | 1.843 (1.422-2.388) | <0.001 |
CPR (> 0.03 vs. ≤ 0.03) | 1.630 (1.140-2.322) | 0.007 |
CAR (> 0.3 vs. ≤ 0.3) | 1.474 (0.992-2.189) | 0.055 |
ESCC: esophageal squamous cell carcinoma; OS: overall survival; TNM: tumor, node, metastasis; BMI: body mass index; CPR: C-reactive protein to prealbumin ratio; CAR: C-reactive protein to albumin ratio; CI: confidence interval; HR: hazard ratio.
The AUC area of the CPR (0.728, 95% CI: 0.678-0.774) was higher than that of CAR (0.702, 95% CI: 0.651-0.750), CRP (0.702, 95% CI: 0.651-0.750), ALB (0.573, 95% CI: 0.519-0.625), and PALB (0.686, 95% CI: 0.635-0.735) for all the ESCC patients (Figure
Comparison of AUC areas for the prognostic factors in ESCC.
AUC | 95% CI | P-value | |
---|---|---|---|
CPR | 0.728 | 0.678-0.774 | Reference |
CAR | 0.702 | 0.651-0.750 | 0.0015 |
CRP | 0.702 | 0.651-0.750 | 0.0008 |
ALB | 0.573 | 0.519-0.625 | 0.0001 |
PALB | 0.686 | 0.635-0.735 | 0.2161 |
ESCC: esophageal squamous cell carcinoma; CRP: C-reactive protein; PALB: prealbumin; ALB: albumin; CPR: C-reactive protein to prealbumin ratio; CAR: C-reactive protein to albumin ratio; AUC: area under the curve.
To the best of our knowledge, this is the first study to investigate the prognostic role of CPR in patients with ESCC. Our study demonstrated some important findings: (1) CPR was a strong predictor of CSS and OS; (2) CPR, instead of CAR, CRP, ALB, or PALB, was a useful independent predictive indicator.
Related studies have shown that the presence of systematic inflammatory response and malnutrition are responsible for the poor prognosis in patients with cancers [
Currently, as a serum index for the assessment on nutritional status, PALB has become a research focus, with it being reported as another important biomarker for nutritional status in recent studies, which is more sensitive to malnutrition than ALB [
Currently, PALB, serving as an important biomarker for nutritional status, has become a research focus due to shorter half-life than ALB [
Another index for assessing nutritional status was BMI. Obesity is showing a rising trend worldwide with the improvement of living standards. It had been reported that the BMI was associated with the prognosis in EC [
Limitations should be acknowledged in this study. The study is mainly limited by its retrospective character and the relatively small samples in a single center. Moreover, patients who received preoperative treatment, such as chemotherapy and/or radiotherapy, were excluded, which might influence the result of this study. Moreover, it is commonly acknowledged that neoadjuvant treatment will generate a side effect on CRP, ALB, and PALB. However, neoadjuvant treatment can improve cancer prognosis for locally advanced ESCC, but not for ESCC at the early stage [
The study is the first time for us to identify (CRP/PALB) CPR and determine its prognostic value in ESCC patients undergoing esophagectomy. Our results revealed that CPR was an effective and independent predictor in resectable ESCC patients with the optimum cut-off point of 0.03.
The data used to support the findings of this study are included within the Supplementary Materials file.
The authors have no conflicts of interest to disclose.
Ji-Feng Feng and Xun Yang conceived and designed the study. Ji-Feng Feng, Liang Wang, and You-Hua Jiang collected the clinical baseline characteristics and drafted the manuscript. Liang Wang carried out the follow-up. Ji-Feng Feng and Liang Wang performed the data analyses and statistical analyses. You-Hua Jiang and Xun Yang checked the data and revised the manuscript. Ji-Feng Feng and Xun Yang conceived the study and helped to draft and approve the manuscript. All authors read and approved the final manuscript.
This study was funded by the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (nos. 2018KY290 and 2019RC129 to FJF and no. 2019RC128 to WL).
The data used to support the findings of this study.