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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 3  |  Page : 171-175

A study of human carcinoembryonic antigen as a biomarker for assessing the severity of stroke


1 Department of Medicine, Ramaiah Medical College, Bangalore, Karnataka, India
2 Fortis Hospital, Bangalore, Karnataka, India

Date of Submission24-Dec-2020
Date of Decision07-Feb-2021
Date of Acceptance16-Feb-2021
Date of Web Publication16-Jul-2021

Correspondence Address:
Dr. Vishwanath Krishnamurthy
Department of Medicine, Ramaiah Medical College, Bangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_110_20

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  Abstract 


Background and Objectives: Human carcinoembryonic antigen (CEA) is widely used as a tumor marker. Striking similarities have been reported between process of tumor genesis and atherosclerotic diseases. CEA levels have also been associated with development of atherosclerosis; there are not many studies on the use of CEA as a biomarker in prognostication of stroke. This study was aimed at evaluating the role of CEA as a marker of severity and as a prognostic marker in patients with acute ischemic stroke. Materials and Methods: A hospital-based case–control study was conducted at a tertiary care hospital in Bangalore. Sixty-eight individuals above 18 years of age were divided into two groups with 34 individuals each: Group A (ischemic stroke) and Group B (age- and sex-matched healthy controls). Exclusion criteria for Group A included diabetes mellitus, heavy smoking, and recent cerebrovascular or myocardial events. The blood sample was taken not later than 24 h of onset of stroke in Group A. CEA levels were estimated using double-sandwich ELISA method. CEA was compared in both the groups. Data were analyzed using statistical software SPSS version 21. Results: The mean standard error serum CEA levels in ischemic stroke patients (cases) and healthy controls were 5.67 ± 1.64 and 0.973 ± 0.21 ng/mL, respectively (P < 0.001). This was significant even after adjusting for confounders. The cases were further divided into three quartiles based on CEA levels. The mean duration of hospital stay, mortality and higher National Institutes of Health Stroke Scale scores, and poor improvement in grade of power were seen in cases under higher CEA quartile (>7 ng/ml) group. The difference was statistically significant. Conclusion: Patients with ischemic stroke have raised level of CEA. CEA is a promising novel biomarker for assessing the severity of acute ischemic stroke.

Keywords: Atherosclerosis, carcinoembryonic antigen, ischemia, stroke


How to cite this article:
Krishnamurthy V, Srinivas S, Jayaram SK, Narayan A, Reddy M, Patted A. A study of human carcinoembryonic antigen as a biomarker for assessing the severity of stroke. APIK J Int Med 2021;9:171-5

How to cite this URL:
Krishnamurthy V, Srinivas S, Jayaram SK, Narayan A, Reddy M, Patted A. A study of human carcinoembryonic antigen as a biomarker for assessing the severity of stroke. APIK J Int Med [serial online] 2021 [cited 2021 Jul 29];9:171-5. Available from: https://www.ajim.in/text.asp?2021/9/3/171/321654




  Introduction Top


Stroke occurs due to the abrupt interruption of cerebral blood flow resulting in neurological deficits. It is a sudden neurological deficit of vascular origin. It is more a clinical syndrome rather than a single disease and is an important cause of disability.[1] There are several assessments from clinical examination to scorings and neuroimaging which are used in predicting the prognosis of stroke patients on admission, despite the availability of all these resources, it is difficult to predict which group of patients do well and which set of patients have a bad prognosis.Thus,the quest to identify newer biomarkers which can effectively predict the prognosis of stroke at triage itself continues. Carcinoembryonic antigen (CEA) is one such laboratory parameter which has been studied in this regard. There are evidences which have shown that CEA levels are increased in atherosclerosis,[2] consequent to which multiple studies have been done on CEA in stroke. These studies have used CEA as a diagnostic marker in stroke. However, not many published literatures are there where it has been used to assess the severity and prognosis of stroke. This study was planned to evaluate the use of CEA to assess its utility as a severity and a prognostic marker in acute stroke.

Aims and objectives of the study

We aimed to assess the correlation between severity and prognosis of stroke with CEA levels.


  Materials and Methods Top


This study was conducted at a tertiary care hospital in Karnataka. It was a case–control study.

After obtaining informed consent, the individuals were enrolled in the study.

A detailed history and physical examination were done on all the individuals along with relevant investigations. Cardiac evaluation was done as a routine in all cases of acute ischemic stroke. A total of 68 individuals (two groups) were enrolled.

Group A comprised patients with acute ischemic stroke, presenting within 24 h of onset of symptoms. Group B was healthy controls (age- and sex comorbidity-matched healthy individuals).

Acute stroke was diagnosed based on clinical features and radiological parameters.[3] Two milliliters of venous blood samples was collected within 24 h of onset of stroke in Group A. In Group B, the blood samples were drawn at the time of enrolment in the study. The study period was 2 years between 2018 and 2020.

CEA levels (for cases and controls) were estimated using double-standard ELISA method. Commercially, available kits (Weldon Biotech) were used for quantitative assessment of CEA.

Sample size

The sample size was calculated based on a previous study conducted by Ranga et al.[4] who found that the mean serum CEA levels in healthy controls and acute stroke patients were 0.95 (0.60) and 5.57 (1.09) which is mean (standard deviation). In the present study, considering mean difference of 0.6 ng/ml, effect size of 0.7, alpha error of 5%, and power of 80%, the sample size was estimated to be 34 in each group where Group A is all patients with acute stroke and controls are healthy patient's attendants.

Statistical analysis

All the quantitative variables like age, laboratory values were expressed in terms of descriptive statistics such as mean, and standard deviation. All the categorical variable such as presence of comorbidities, were expressed in terms of percentages. Difference in the mean values of serum CEA levels and other study parameters between the case and control groups were tested for statistical significance by student t test.

Inclusion criteria

  • Males and females aged >18 years with the first episode of a cerebrovascular event (acute ischemic stroke) presenting to the hospital within 24 h of onset of symptoms were included in the study.


Exclusion criteria

  • Previous history of cerebrovascular event
  • Recent Myocardial Infarction (<3 months)
  • Chronic kidney disease (CKD)
  • Chronic obstructive pulmonary disease
  • Obesity
  • Heavy smoking (>12 pack-years)
  • History of carcinoma, chemotherapy/radiotherapy
  • History of chronic bowel disorders, inflammatory bowel disease, pancreatitis, and cirrhosis of the liver
  • Hypothyroidism.



  Results Top


There was no statistically significant difference found between cases and controls with respect to age group, sex distribution, and risk factors [Table 1].
Table 1: Distribution of individuals among cases and controls

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There was a statistically significant difference in serum creatinine, triglycerides, and low-density lipoprotein. However, there was no difference in other parameters [Table 2].
Table 2: Laboratory parameter comparison among cases and controls

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There was a statistically significant difference found in the mean CEA between the case and control groups (P < 0.001) [Table 3].
Table 3: Comparison of mean carcinoembryonic antigen between cases and controls

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In our study, cases were divided into three quartiles: first quartile with CEA <5 ng/ml, second quartile with CEA between 5 and 7 ng/ml, and third quartile with CEA more than 7 ng/ml.

Subsequent results are based on these three quartiles.

There was a statistically significant difference between the mean duration of hospital stay and intensive care unit (ICU) stay with different quartiles of CEA levels and which was more with CEA >7 ng/ml range [Table 4].
Table 4: The mean hospital stay, mean intensive care unit stay, and mortality with different quartiles of carcinoembryonic antigen levels among the cases

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The maximum number of cases belonged to the quartile 5–7 ng/ml of CEA in cases.

Mortality was seen in cases with higher CEA levels (>7 ng/ml) among the different quartiles of CEA levels.

There was a statistically significant difference between the National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge within different quartiles of CEA levels.

It showed a statistically significant difference in NIHSS score. [Table 5] and in the power on examination within different quartiles of CEA levels. It was noted that mean power was lower with higher CEA levels coupled with poor improvement. [Table 6].
Table 5: National Institutes of Health Stroke Scale score at admission and discharge in cases with different quartiles of carcinoembryonic antigen level

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Table 6: Mean power in all four limbs at admission in cases with different quartiles of carcinoembryonic antigen levels

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  Discussion Top


Human CEA is the prototypic member of a family of highly related cell surface glycoproteins that include CEA-related cell adhesion molecule 6 and others. It is a nonspecific tumor antigen. CEA is usually present at very low levels in the blood of healthy adults.[5] It is not only elevated in neoplastic conditions such as colon and lung cancers. It is also elevated in CKD, inflammatory bowel disease, obesity, atherosclerosis, etc.[6] The biological properties and function of CEA, which facilitate the increase in the production of proinflammatory cytokines chemotaxis, adhesion and angiogenesis may also explain its probable mechanism in atherosclerosis.[7],[8],[9] There are several reasons for elevation of CEA in stroke patients; one of the important points is its association with atherosclerosis. Serum CEA levels are found to be associated with early carotid atherosclerosis, and this association was independent of other atherogenic risk factors as well as markers of inflammation.[2]

Although evidences have shown that CEA levels are increased in atherosclerosis,[2] there are no established studies showing correlation of CEA levels and prognosis of acute coronary syndrome (ACS), however, a study by Ranga et al.[4] has shown that serum levels of CEA show a strong positive correlation with creatine phosphokinase-MB levels in patients with myocardial infarction, which in turn shows a significant correlation with severity of ACS, thus showing an indirect positive correlation.

Our study was a case–control study. Cases (N-34) were ischemic stroke patients fulfilling inclusion and exclusion criteria. controls (N-34) were age, gender,comorbidity matched healthy volunteers. CEA level was studied in the Ischemic and control groups.

The mean age was 54.0 ± 4.8 and 54.7 ± 4.8 years, respectively, in both the groups.

In a case–control study done by Ranga et al.,[4] in Delhi with 60 individuals, the mean age was 51.0 ± 4.8 and 51.7 ± 4.8 years, respectively, in both the groups.

The range of age was 42–59 years in both the groups. There was no statistically significant difference in the case and control groups with respect to comorbidities. Twenty-three (76.6%) patients with acute ischemic stroke were hypertensive, while 11 of the controls were hypertensive.

Blood parameters, including hemoglobin, blood urea, serum creatinine, liver function tests, and lipid parameters, were comparable in both the groups.

The mean CEA level in patients with ischemic stroke was 5.67 ± 1.64 ng/ml, and majority (50%) belonged to CEA class interval of 5–7 ng/ml. The mean CEA level in the control group was 0.973 ± 0.21 ng/ml, and majority (75%) had values <2.5 ng/ml. The difference in CEA level between the case and control groups is statistically significant (P < 0.001). This was similar to a study done by Ranga et al.[4] and Perumal et al.[10]

Among 34 cases enrolled, 25 patients had CEA more than 5 ng/ml. Even in cases who had CEA <5 ng/ml, the mean CEA level was 3.4 which was higher than the mean in the control group (P < 0.001).

In our study, cases were further divided into three quartiles: first quartile with CEA <5 ng/ml, second quartile with CEA between 5 and 7 ng/ml, and third quartile with CEA more than 7 ng/ml, and analysis was done.

In quartile with CEA level >7 ng/ml, the mean hospital stay was 8.57 days, and in cases with CEA <5 ng/ml, the mean duration of hospital stay was 4.61 days. The difference was significant (P < 0.001). There were 4 in hospital mortality among 34 cases, all of them were in the quartile of CEA >7 ng/ml death was due to complicated acute ischemic stroke, and the mean CEA value in these patients who died was 7.7.

The mean duration of ICU stay in cases with CEA >7 ng/ml was 2.25 days, and in cases with CEA <5 ng/ml, the mean duration of ICU stay was 1.05 days (P < 0.001). Thus, implying higher CEA levels were associated with increasing severity.

In this study, we correlated the levels of CEA and NIHSS score on admission, and to see if the levels of CEA can be used to assess the prognosis. The NIHSS was developed to help physicians objectively rate the severity of ischemic strokes. Increasing scores indicate a more severe stroke and have been shown to correlate with the size of the infarction on both computed tomography and magnetic resonance imaging evaluation. NIHSS scores when assessed within the first 48 h following a stroke have been shown to correlate with clinical outcomes at the 3-month and 1-year mark.[11]

Higher NIHSS scores (>20) were more in cases with CEA levels >7 and lower NIHSS scores were seen as the CEA levels were low. The difference was statistically significant (P < 0.010), thus underlying the fact that that CEA levels can be used to assess the severity and prognosis. This is a significant finding as measurement of CEA being an objective parameter will negate an important limitation[11] of NIHSS scoring, which is the interobserver variability bias.

A further subanalysis was done among cases, by assessing the grade of power of all four limbs (depending on side of involvement and excluding patients who died) at admission and discharge. In cases with higher CEA levels, the mean power at admission and discharge was 2 and 2.35 (P < 0.001). In cases with CEA <5 ng/ml, the mean power at admission and discharge was 3.9 and 4.37 (P < 0.001), respectively. This demonstrated that higher CEA levels were associated with lower grades of muscle power and the difference was statistically significant.

Thus, CEA levels at admission were able to prognosticate the patients with stroke.

This study is unique in a way that it tried to assess the severity and prognosis of the stroke patients by correlating CEA values with NIHSS score and also improvement assessed by noting one of the important clinical parameters of improvement in grade of power of limbs which is a vital component of activity of daily living assessment in stroke patients The limitation of this study is the sample size.

To the best of our knowledge, there are no previous standard studies, where they have used CEA levels to assess the severity and the prognosis of stroke by comparing the NIHSS score on admission and also comparing the power of limbs at admission and discharge (patients who died were excluded). Further multicentric prospective studies with large sample size may add to the existing knowledge. Levels of CEA can be added to existing scoring systems in prognostication of stroke patients to increase the accuracy of the same.

The results of our study confirm and expand previous findings, showing that CEA may prove to be a promising biomarker for early diagnosis and prognosis of acute ischemic stroke. It may have very useful diagnostic value in situations where imaging gives ambiguous results.


  Conclusion Top


The CEA levels are higher among ischemic stroke patients than normal population. Along with the clinical presentation, radiological findings, CEA can also be used as a prognostic marker in acute stroke

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bath PM, Lees KR. Acute stroke. West J Med 2000;173:209-12.  Back to cited text no. 1
    
2.
Ishizaka N, Ishizaka Y, Toda E, Koike K, Yamakado M, Nagai R. Are serum carcinoembryonic antigen levels associated with carotid atherosclerosis in Japanese men? Arterioscler Thromb Vasc Biol 2008;28:160-5.  Back to cited text no. 2
    
3.
Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, et al. An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:2064-89.  Back to cited text no. 3
    
4.
Ranga GS, Bansal N, Sharma SB, Avasthi R. Human carcinoembryonic antigen is a useful biomarker for diagnosis of acute stroke. Neurol Asia 2016;21:1-6.  Back to cited text no. 4
    
5.
Rizeq B, Zakaria Z, Ouhtit A. Towards understanding the mechanisms of actions of carcinoembryonic antigen-related cell adhesion molecule 6 in cancer progression. Cancer Sci 2018;109:33-42.  Back to cited text no. 5
    
6.
Stevens DP, Mackay IR. Increased carcinoembryonic antigen in heavy cigarette smokers. Lancet 1973;2:1238-9.  Back to cited text no. 6
    
7.
Vassalle C, Pratalli L, Ndreu R, Battaglia D, Andreassi MG. Carcinoembryogenic antigen concentrations in patients with acute coronary syndrome. Clin Chem Lab Med 2010;48:1339-43.  Back to cited text no. 7
    
8.
Ganguly A, Yeltsin E, Robbins J. Identification of a carcinoembryonic antigen binding protein on monocytes. Biochem Biophys Res Commun 2003;311:319-23.  Back to cited text no. 8
    
9.
Aarons CB, Bajenova O, Andrews C, Heydrick S, Bushell KN, Reed KL, et al. Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells. Clin Exp Metastasis 2007;24:201-9.  Back to cited text no. 9
    
10.
Perumal V, Narayanan N, Mohanan J, Rangarajan J, Kalifa M, Uma Maheshwari, et al. Study on clinical profile, complications and outcome of copper sulphate poisoning at a tertiary care centre in South India. J. Evolution Med. Dent. Sci. 2016;5:3440-4, DOI: 10.14260/jemds/2016/794.  Back to cited text no. 10
    
11.
Runde D. NIH Stroke Scale/Score (NIHSS)-Mdcalc; 2020. Available from: https://www.mdcalc.com/nih-stroke-scale-score-nihss#pearls-pitfalls. [Last accessed on 2020 Dec 23].  Back to cited text no. 11
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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