Trajectories of perioperative serum carcinoembryonic antigen and colorectal cancer outcome: A retrospective, multicenter longitudinal cohort study.
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SUBMITTER: Li Z
PROVIDER: S-EPMC7818970 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
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Trajectories of perioperative serum carcinoembryonic antigen and colorectal cancer outcome: A retrospective, multicenter longitudinal cohort study.
Li Zhenhui Z Li Chunxia C Pu Hongjiang H Pang Xiaolin X Wang Yingyi Y Zhang Dafu D Lei Ming M Cheng Xianshuo X Zhao Yanrong Y Lu Guiyu G Ding Yingying Y Cai Le L Liu Zaiyi Z Zhang Tao T You Dingyun D
Clinical and translational medicine 20210201 2
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Project description:BackgroundThe dynamic monitoring of perioperative carcinoembryonic antigen (CEA) is recommended by current colorectal cancer (CRC) guidelines, while the benefits of additional measurements of carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125) have remained controversial.MethodsThis retrospective longitudinal cohort included 3539 CRC patients who underwent curative resection. Distinct trajectory groups were identified by the latent class growth mixed model. Patients were grouped into subgroups jointly by CEA, CA19-9, and CA125 according to preoperative levels and longitudinal trajectories, respectively. The end points were overall survival (OS) and recurrence-free survival (RFS).FindingsThree distinct trajectory groups were characterized for serum CEA, CA19-9, and CA125: low-stable, early-rising, and later-rising. Jointly, patients were grouped into six preoperative (trajectory) joint groups. Compared with the three-low group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) associated with death were 1.87 (1.29-2.70), 3.82 (2.37-6.17), 1.87 (0.97-3.61), 2.81 (1.93-4.11), and 4.99 (2.80-8.86) for the CEA-high, CA19-9-high, CA125-high, two-high, and three-high group, respectively. And compared with the three-stable trajectory group, the corresponding HRs (95% CIs) were 1.59 (1.10-2.30), 1.55 (0.77-3.10), 6.25 (4.02-9.70), 4.05 (2.73-6.02), and 12.40 (5.77-26.70) for the five rising trajectory groups, respectively. Similar associations between joint groups and RFS were observed. Notably, the trajectory joint group still had prognostic significance after adjusting for preoperative levels. The CA19-9-high group (HR: 3.82, 95% CI: 2.37-6.17) was associated with higher risk of death than the two-high group (HR: 2.81, 95% CI: 1.93-4.11). Likewise, for the CA125-rising trajectory group and two-rising trajectory group, the HRs (95% CIs) were 6.13 (3.75-10.00) and 3.99 (2.63-6.05) for death, and 3.08 (2.07-4.58) and 2.10 (1.52-2.90) for recurrence.InterpretationIn addition to CEA, the dynamic measurements of CA19-9 and CA125 are recommended to monitor the prognosis of CRC patients.FundingNational Natural Science Foundation of China [81973147, 82001986, 81960592, 82073569, 81660545].
| S-EPMC8605392 | biostudies-literature
Project description:ImportanceGuidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown.ObjectiveTo investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA.Design, setting, and participantsThis retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified.ExposuresPatients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA.Main outcomes and measuresThree-year recurrence-free survival (RFS) and hazard function curves over time were analyzed.ResultsA total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS.Conclusions and relevanceElevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.
| S-EPMC5885834 | biostudies-literature
Project description:BackgroundThe purpose is to investigate prognosis according to serum CEA levels before and after surgery in patients with stage IIA colon cancer who do not show high-risk features.MethodsAmong the patients diagnosed with colon adenocarcinoma between April 2011 and December 2017, 462 patients were confirmed as low-risk stage IIA after surgery and enrolled. The ROC curve was used to determine cut-off values of pre- and postoperative CEA. Patients were classified into three groups using these new cut-off values.ResultsAll recurrence occurred in 52 of 463 patients (11.2%). However, recurrence in group H was 15.9%, which was slightly higher than the other two groups (P = 0.04). Group L and M showed 10.5% and 12.8% overall survival, group H was higher at 21.0% (P = 0.005). Recurrence was the only risk factor in group H was significantly higher in group L (HR 2.008, 95% CI, 1.123-3.589, P = 0.019). Mortality was similar to recurrence (HR 1.975, 95% CI 1.091-3.523, P = 0.044).ConclusionAmong patients with low-risk stage IIA colon cancer, recurrence and mortality rates were higher when perioperative serum CEA levels were above a certain level. Therefore, high CEA level should be considered a high-risk feature and adjuvant chemotherapy should be performed.
| S-EPMC8189445 | biostudies-literature
Project description:Serum carcinoembryonic antigen (CEA) levels can help predict the prognosis of colorectal cancer patients. Accordingly, high preoperative CEA levels that is not restored after surgery are indicative of a worse outcome. On the other hand, smoking can increase serum CEA levels independently of the disease status. Thus, we aimed to evaluate the impact of smoking on the prognostic value of serum CEA levels. This retrospective cohort study included 273 patients who underwent curative resection for stage I-III colorectal adenocarcinoma at a single institution, between January 2010 and December 2017. Patients were grouped as follows: group A, normal preoperative and postoperative CEA levels (n = 152); group B, elevated preoperative CEA levels that returned to reference values after surgery (n = 69); and group C, elevated postoperative serum CEA levels (n = 52). Patients were also grouped according to their smoking history: group S (current smokers, n = 79) and group NS (never and former smokers, n = 194). Group A showed a higher 3-year disease-free survival (DFS) rate (84.9%) than groups B (75.4%) and C (62.0%) (p < 0.001). Postoperative serum CEA levels were significantly higher in the S group than in the NS group (2.6 vs. 3.1 ng/mL, p = 0.009), whereas preoperative levels were similar (3.8 vs. 4.1, p = 0.182). Further, smokers showed higher 3 year-DFS rates than nonsmokers in group C (83.3% vs. 43.9%, p = 0.029). This suggests that while elevated postoperative CEA levels are associated with lower DFS rates in never and former smokers, they are not associated with lower DFS rates in current smokers. We conclude that persistent smoking alters the prognostic value of postoperative serum CEA levels in colorectal cancer patients and that, consequently, alternative surveillance strategies need to be developed for colon cancer patients with smoking habits.
| S-EPMC7274431 | biostudies-literature
Project description:Carcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94-3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.
| S-EPMC8463604 | biostudies-literature
Project description:BACKGROUND:In colorectal cancer, survival of patients is drastically reduced when complete resection is hampered by involvement of critical structures. Targeted photodynamic therapy (tPDT) is a local and targeted therapy which could play a role in eradicating residual tumor cells after incomplete resection. Since carcinoembryonic antigen (CEA; CEACAM5) is abundantly overexpressed in colorectal cancer, it is a potential target for tPDT of colorectal cancer. METHODS:To address the potential of CEA-targeted PDT, we compared colorectal cancer cell lines with different CEA-expression levels (SW-48, SW-480, SW-620, SW-1222, WiDr, HT-29, DLD-1, LS174T, and LoVo) under identical experimental conditions. We evaluated the susceptibility to tPDT by varying radiant exposure and concentration of our antibody conjugate (DTPA-hMN-14-IRDye700DX). Finally, we assessed the efficacy of tPDT in vivo in 18 mice (BALB/cAnNRj-Foxn1nu/nu) with subcutaneously xenografted LoVo tumors. RESULTS:In vitro, the treatment effect of tPDT varied per cell line and was dependent on both radiant exposure and antibody concentration. Under standardized conditions (94.5 J/cm2 and 0.5 μg/μL antibody conjugate concentration), the effect of tPDT was higher in cells with higher CEA availability: SW-1222, LS174T, LoVo, and SW-48 (22.8%, 52.8%, 49.9%, and 51.9% reduction of viable cells, respectively) compared to cells with lower CEA availability. Compared to control groups (light or antibody conjugate only), tumor growth rate was reduced in mice with s.c. LoVo tumors receiving tPDT. CONCLUSION:Our findings suggest cells (and tumors) have different levels of susceptibility for tPDT even though they all express CEA. Furthermore, tPDT can effectively reduce tumor growth in vivo.
| S-EPMC6906275 | biostudies-literature
Project description:BackgroundPatients with stage I lung adenocarcinoma (LUAD) have varying postoperative prognosis. This study aimed to investigate the prognostic significance of postoperative longitudinal change of serum carcinoembryonic antigen (CEA) level in patients with stage I LUAD.MethodsThe study cohort comprised 241 patients with stage I LUAD completely resected with single-port video-assisted thoracic surgery (VATS). The patients were categorized into 4 groups according to the postoperative longitudinal change of serum CEA levels measured in the third and sixth months after surgery: the NN group (continuously normal), HN group (increase first and then decrease), NH group (decrease first and then increase), and HH group (continuously high). Recurrence-free survival (RFS) was analyzed by the Kaplan-Meier method and compared by log-rank test. A nomogram was developed to predict recurrence in the stage I LUAD patients.ResultsIn univariate analysis, differentiation (P<0.001), visceral pleural invasion (VPI) (P=0.025), tumor diameter (P<0.001), tumor-node-metastasis (TNM) stage (P=0.008), preoperative CEA levels (≥10.0 vs. <10.0 ng/mL, P<0.001), and postoperative CEA grouping (NH/HH vs. NN/HN, P<0.001) were significant prognostic factors for stage I LUAD patients. Multivariate analysis showed that tumor diameter (P=0.009) and postoperative CEA grouping (P<0.001) were considered to be independent prognostic factors of postoperative recurrence of stage I LUAD. Tumor diameter (≥20 mm) and postoperative CEA (NH/HH vs. NN/HN) were associated with worse RFS. Receiver operating characteristic (ROC) curve analysis showed that postoperative CEA (NH/HH vs. NN/HN) have high sensitivity (64.7%) and specificity (83.2%) for early prediction of postoperative recurrence of stage I LUAD. The area under curve (AUC) value was 0.745. The nomogram based on multivariate Cox regression had a concordance index (value of 0.789). The calibration plot showed that the predicted probabilities closely matched the observed probabilities.ConclusionsLongitudinal change in serum CEA level after surgery was found to be an independent unfavorable prognostic factor in completely resected stage I LUAD patients. The NH group and HH group were significantly associated with worse RFS. A nomogram was established to predict the postoperative recurrence of patients with stage I LUAD.
| S-EPMC8577984 | biostudies-literature
Project description:BackgroundColorectal cancer-specific biomarkers have been used as molecular targets for fluorescent intra-operative imaging, targeted PET/MRI, and selective cytotoxic drug delivery yet the selection of biomarkers used is rarely evidence-based. We evaluated sensitivities and specificites of four of the most commonly used markers: carcinoembryonic antigen (CEA), tumour-associated glycoprotein-72 (TAG-72), folate receptor-? (FR?) and Epithelial growth factor receptor (EGFR).MethodsMarker expression was evaluated semi-quantitatively in matched mucosal and colorectal cancer tissues from 280 patients using immunohistochemistry (scores of 0-15). Matched positive and negative lymph nodes from 18 patients were also examined.ResultsMarkers were more highly expressed in tumour tissue than in matched normal tissue in 98.8%, 79.0%, 37.1% and 32.8% of cases for CEA, TAG-72, FR? and EGFR, respectively. Carcinoembryonic antigen showed the greatest differential expression, with tumours scoring a mean of 10.8 points higher than normal tissues (95% CI 10.31-11.21, P<0.001). Similarly, CEA showed the greatest differential expression between positive and negative lymph nodes. Receiver operating characteristic analyses showed CEA to have the best sensitivity (93.7%) and specificity (96.1%) for colorectal cancer detection.ConclusionCarcinoembryonic antigen has the greatest potential to allow highly specific tumour imaging and drug delivery; future translational research should aim to exploit this.
| S-EPMC3593555 | biostudies-literature
Project description:PurposeAlthough serum CEA and CA 19-9 have been widely utilized for the diagnosis of gallbladder cancer (GBC), few studies have examined the diagnostic performance of them. This study aimed to investigate the diagnostic performance of these 2 biomarkers and demonstrate their clinical usefulness in diagnosing GBC.MethodsBetween January 2000 and March 2020, a total of 751 GBC patients and 2,310 normal controls were included. Serum CEA and CA 19-9 were measured preoperatively. Receiver operating characteristic curves were obtained, and the sensitivity and specificity of each biomarker were evaluated.ResultsIn terms of differentiating GBC from the control, the sensitivity and specificity of serum CEA at 5 ng/mL was 12.1% and 99.1%, respectively, and those of serum CA 19-9 at 37 IU/mL were 28.7% and 94.5%, respectively. The optimal cutoff values of CEA and CA 19-9 were set to 2.1 ng/mL and 26 IU/mL in the receiver operating characteristic curves, respectively. The sensitivities of CEA and CA 19-9 at new cutoff values slightly increased but remained low (CEA, 42.9%; CA 19-9, 38.2%). When differentiating early-stage GBC from advanced tumor, the sensitivity and specificity, were 14.2% and 96.1% for CEA (cutoff value, 5 ng/mL) and 33.6% and 90.1% for CA 19-9 (cutoff value, 37 IU/mL), respectively.ConclusionSerum CEA and CA 19-9 levels are not suitable for screening GBC patients from controls. New promising biomarkers with higher sensitivity should be explored.
| S-EPMC8564080 | biostudies-literature
Project description:Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker used in clinical applications. The primarily clinical method for measuring CEA is based on chemiluminescence in serum during enzyme-linked immunosorbent assays (ELISA) in 96-well plates. However, this multi-step process requires large and expensive instruments, and takes a long time. In this study, a high-throughput centrifugal microfluidic device was developed for detecting CEA in serum without the need for cumbersome washing steps normally used in immunoreactions. This centrifugal microdevice contains 14 identical pencil-like units, and the CEA molecules are separated from the bulk serum for subsequent immunofluorescence detection using density gradient centrifugation in each unit simultaneously. To determine the optimal conditions for CEA detection in serum, the effects of the density of the medium, rotation speed, and spin duration were investigated. The measured values from 34 clinical serum samples using this high-throughput centrifugal microfluidic device showed good agreement with the known values (average relative error = 9.22%). These results indicate that the high-throughput centrifugal microfluidic device could provide an alternative approach for replacing the classical method for CEA detection in clinical serum samples.
| S-EPMC6187594 | biostudies-literature