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The prognostic value of preoperative serum CA724 for CEA-normal colorectal cancer patients.

ABSTRACT: Background and Purpose:There had been no recognized serum tumor marker to predict the prognosis of colorectal cancer (CRC) patients with normal preoperative serum carcinoembryonic antigen (CEA) levels. The purpose of this study was to determine whether preoperative serum carbohydrate antigen 724 (CA724) was of predictive function for the prognosis of CRC patients with normal CEA levels. Methods:The medical records of 295 CRC patients with normal CEA levels who underwent surgery at the Department of Colorectal Anal Surgery of the First Affiliated Hospital of Guangxi Medical University (Guangxi, China) between September 2012 and September 2014 were retrospectively reviewed. The Chi-square test was used to test the correlation between preoperative serum CA724 levels and clinical features. Kaplan-Meier curves were conducted to calculate the overall survival (OS) rate and disease-free survival (DFS) of patients. Cox regression analysis was applied to conduct univariate and multivariate analysis of the following four preoperative serum tumor makers namely CA724, carbohydrate antigen 199 (CA199), carcinoembryonic antigen 125 (CA125), carcinoembryonic antigen 242 (CA242) and clinical features. Nomograms for prognostic parameter of OS and DFS were developed using R v3.2.5. Results:In the Chi-square test, only pathological node stage (pN stage) (X 2 = 14.514, P = 0.001) and differentiation (X 2 = 10.712, P = 0.001) were associated with serum CA724 levels. In the Kaplan-Meier analysis, the results revealed that the OS and DFS in patients with high CA724 was poorer than those with normal. In the multivariate Cox regression analysis of OS and DFS, only pT stage, pN stage, metastasis and serum CA724 were independent prognostic risk factors for CRC patients with normal CEA levels. Conclusion:Preoperative serum CA724 might serve as a potential prognostic factor for CRC patients with normal serum CEA levels.

SUBMITTER: Kuang J

PROVIDER: S-EPMC7164426 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The prognostic value of preoperative serum CA724 for CEA-normal colorectal cancer patients.

Kuang Jiaan J Gong Yizhen Y Xie Hailun H Yan Ling L Huang Shizhen S Gao Feng F Tang Shuangyi S Gan Jialiang J

PeerJ 20200414

<h4>Background and purpose</h4>There had been no recognized serum tumor marker to predict the prognosis of colorectal cancer (CRC) patients with normal preoperative serum carcinoembryonic antigen (CEA) levels. The purpose of this study was to determine whether preoperative serum carbohydrate antigen 724 (CA724) was of predictive function for the prognosis of CRC patients with normal CEA levels.<h4>Methods</h4>The medical records of 295 CRC patients with normal CEA levels who underwent surgery at ...[more]

PMID: 32328348

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Project description:ObjectiveWhether preoperative serum carbohydrate antigen 19-9 (CA19-9) is an independent prognostic factor and there are interactions of serum CA19-9 with carcinoembryonic antigen (CEA) on the risk of recurrence in colorectal cancer (CRC) patients are still not clarified.MethodsConsecutive patients with CRC who underwent curative resection for stage II-III colorectal adenocarcinoma at five hospitals were collected. Based on Cox models, associations of preoperative CA19-9 with recurrence-free survival (RFS) and overall survival (OS) were evaluated in patients with or without elevated CEA, and interactions between CEA and CA19-9 were also calculated. Restricted cubic spline (RCS) curves were used to evaluate the associations between preoperative CA19-9 and CRC outcomes on a continuous scale.ResultsA total of 5048 patients (3029 [60.0%] men; median [interquartile range, IQR] age, 61.0 [51.0, 68.0] years; median [IQR] follow-up duration 46.8 [36.5-62.4] months) were included. The risk of recurrence increased with the elevated level of preoperative CA19-9, with the slope steeper in patients with normal CEA than those with elevated CEA. Worse RFS was observed for elevated preoperative CA19-9 (> 37 U/mL) (n = 738) versus normal preoperative CA19-9 (≤ 37 U/mL) (n = 4310) (3-year RFS rate: 59.4% versus 78.0%; unadjusted hazard ratio [HR]: 2.02; 95% confidence interval [CI]:1.79 to 2.28), and significant interaction was found between CA19-9 and CEA (P for interaction = 0.001). Increased risk and interaction with CEA were also observed for OS. In the Cox multivariable analysis, elevated CA19-9 was associated with shorter RFS and OS regardless of preoperative CEA level, even after adjustment for other prognostic factors (HR: 2.08, 95% CI:1.75 to 2.47; HR: 2.25, 95% CI:1.80 to 2.81). Subgroup analyses and sensitivity analyses yielded largely similar results. These associations were maintained in patients with stage II disease (n = 2724).ConclusionsPreoperative CA19-9 is an independent prognostic factor in CRC patients. Preoperative CA19-9 can be clinically used as a routine biomarker for CRC patients, especially with preoperative normal serum CEA.

Project description:BackgroundSerum carcinoembryonic antigen (CEA) is an important biomarker for diagnosis, prognosis, recurrence, metastasis monitoring, and the evaluation of the effect of chemotherapy in colorectal cancer (CRC). However, few studies have focused on the role of early postoperative CEA in the prognosis of stage II CRC.MethodsPatients with stage II CRC diagnosed between January 2007 and December 2015 were included. Receiver operating characteristic (ROC) curves were used to obtain the cutoff value of early postoperative CEA, CEA ratio and CEA absolute value. The areas under curves (AUCs) were used to estimate the predictive abilities of the CEA and T stage. The stepwise regression method was used to screen the factors included in the Cox regression analysis. Before and after propensity score (PS) - adjusted Cox regression and sensitivity analysis were used to identify the relationship between early postoperative CEA and prognosis. Meta-analysis was performed to verify the results. Kaplan-Meier survival curves were used to estimate the effects of CEA on prognosis.ResultsWe included 1081 eligible patients. ROC curves suggested that the cutoff value of early postoperative CEA was 3.66 ng/ml (P <0.001) and the AUC showed early postoperative CEA was the most significant prognostic marker in stage II CRC (P = 0.0189). The Cox regression and sensitivity analysis before and after adjusting for PS both revealed elevated early postoperative CEA was the strongest independent prognostic factor of OS, DFS, and CSS (P < 0.001). Survival analysis revealed that patients with elevated early postoperative CEA had lower OS (53.62% VS 84.16%), DFS (50.03% VS 86.75%), and CSS (61.77% VS 90.30%) than patients with normal early postoperative CEA (P < 0.001). When the postoperative CEA was positive, the preoperative CEA level showed no significant effect on the patient's prognosis (all P-values were > 0.05). Patients with a CEA ratio ≤0.55 or CEA absolute value ≤-0.98 had a worse prognosis (all P-values were < 0.001). Survival analysis suggested that adjuvant chemotherapy for stage II CRC patients with elevated early postoperative CEA may improve the CSS (P = 0.040).ConclusionsEarly postoperative CEA was a better biomarker for prognosis of stage II CRC patients than T stage and preoperative CEA, and has the potential to become a high-risk factor to guide the prognosis and treatment of stage II CRC patients.

Project description:BackgroundCathepsin X is a cysteine protease involved in mechanisms of malignant progression. It is secreted from tumour cells as a proenzyme and may serve to predict the disease status and risk of death for cancer patients. In a previous, pilot, study on 77 colorectal patients we demonstrated the correlation of higher serum levels with shorter overall survival.Methods264 patients with colorectal cancer were included in a prospectively accrued multi-centre observational cohort study with the aim of testing novel biomarkers. Blood samples were collected before preoperative large bowel endoscopy and total cathepsin X was measured in sera by ELISA. As a control group we selected at random 77 subjects who had no findings at endoscopy and reported no co-morbidity.ResultsThe mean level of cathepsin X in cancer patients did not differ from the control levels (23.4 ng/ml ± 6.4 SD vs. 18.8 ng/ml ± 11.4 SD, p > 0.05) and there was no association with age, gender, disease stage, tumour location or CEA. In univariate analysis no association between cathepsin X levels and overall survival was demonstrated for the entire set of patients, however, cathepsin X was associated with survival in a group of patients with local resectable disease (stages I-III) (HR = 1.69, 95% CI: 1.03-2.75, p = 0.03). For this group, multivariate Cox regression analysis showed an association (HR = 3.13, 95% CI: 1.37-7.18, p = 0.003) between high cathepsin X levels and shorter overall survival for patients who did not receive chemotherapy, whereas, for patients who received chemotherapy, there was no association between cathepsin X and survival (HR = 0.51, 95% CI: 0.20-1.33, p = 0.88).ConclusionsAssociation of cathepsin X levels with overall survival was not confirmed for an entire set of 264 colorectal patients, but for patients in stages I-III with local resectable disease. The significant association of cathepsin X with survival in a group of patients who received no chemotherapy and the absence of this association in the group who received chemotherapy, suggest the possible predictive value for response to chemotherapy. The results have to be confirmed in a further prospective study.

Project description:Background: Carcinoembryonic antigen (CEA) is the most common serum tumor marker in colorectal cancer (CRC). Nevertheless, few previous studies demonstrated the impacts of postoperative CEA and post-preoperative CEA increment on prognosis of CRC. Methods: Patients with stage II and III CRC were included from January 2009 to December 2015. All clinical and follow-up data were collected. Patients were divided into four different groups according to the levels of postoperative serum CEA and post-preoperative CEA trends. Chi-square test was used to analyze the relationship between clinical variables and categorized postoperative CEA and CEA increment. Cox proportional hazard regression was used for univariate and multivariable analyses. The log-rank test was performed to compare PFS and OS among groups. Results: Patients, 1,008, who underwent radical surgery, were enrolled. Our results showed that positive postoperative CEA and CEA increment were related to clinical stage, T stage, N stage, tumor differentiation, and lymphatic invasion (p < 0.05). Univariate and multivariable analysis results suggested that positive postoperative CEA and CEA increment were independent prognostic factors for PFS (HR = 3.149, 95% CI, 2.426-4.088, p = 0.000 for postoperative CEA; HR = 2.708, 95% CI, 2.106-3.482, p = 0.000 for CEA increment) and OS (HR = 3.414, 95% CI, 2.549-4.574, p = 0.000 for postoperative CEA; HR = 2.373, 95% CI, 1.783-3.157, p = 0.000 for CEA increment). The survival analyses revealed positive postoperative CEA, and CEA increment predicted worse prognosis. Furthermore, our results indicated that the 3- and 5-year PFS rates were 86.6 and 78.4% in group A, but decreased to 25.3 and 7.2% in group D (p < 0.001). Similarly, the 3- and 5-year OS rates for group A were 92.5 and 83.9%, much higher than group D (p < 0.001). In other words, patients with both postoperative CEA elevation and CEA increment had the worst prognosis. Conclusions: Positive postoperative CEA and CEA increment were independent prognostic factors for stage II and III CRC. Additionally, postoperative CEA and CEA increment had significant impacts on PFS and OS of CRC.

Project description:The application of serum interleukin-6 (IL-6) in the diagnosis and prognosis of colorectal cancer (CRC) has been evaluated in many studies, whereas the results were contradictive.The aim of this study was to systematically evaluate this issue.An original study was conducted to explore the diagnostic value of serum IL-6 in CRC. Pubmed, Embase, and Cochrane library databases were searched for eligible studies.For diagnostic meta-analysis, aggregate data (AD) and individual participant data (IPD) meta-analyses were both adopted. The sensitivity and specificity were pooled and a summary receiver-operating characteristic (ROC) curve was constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of IL-6 for survival were summarized. Secondary analysis of survival data was performed to synthesize the Kaplan-Meier curves.Total 17 studies (including our study) were included in this meta-analysis. The pooled sensitivity, specificity, and area under curve (AUC) of serum IL-6 were 0.72 (95% CI: 0.46-0.88), 0.74 (95% CI: 0.56-0.86), and 0.79 (95% CI: 0.75-0.82) in CRC diagnosis, respectively. Further, IPD meta-analysis strengthened the diagnostic value of serum IL-6 (the AUC, sensitivity, and specificity were 0.794, 0.606, and 0.839, respectively). For prognostic analysis, the high serum level of IL-6 was inversely associated with overall survival (OS) (pooled HR?=?1.76, 95% CI: 1.42-2.19, P?<?0.001) and disease-free survival (DFS) (pooled HR?=?2.97, 95% CI: 1.76-5.01, P?<?0.001). The synthesized Kaplan-Meier curves indicated that CRC patients with higher serum IL-6 level had a worse OS (P?=?0.0027) and DFS (P?<?0.001), which further support the prognostic value of serum IL-6 in CRC patients.The present study confirmed that serum IL-6 may be a potential biomarker for CRC diagnosis, and the high serum IL-6 level was associated with poor prognosis for both CRC overall survival and disease-free survival. The study has been registered in an international registry of systematic reviews PROSPERO (CRD42013006485).

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The prognostic value of preoperative serum CA724 for CEA-normal colorectal cancer patients.

Publications

The prognostic value of preoperative serum CA724 for CEA-normal colorectal cancer patients.

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