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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 7  |  Page : 215-217

Serum cyfra21-1 as a biomarker in patients with nonsmall cell lung cancer


Department of Thoracic Surgery, Bao Di Hospital, Bao Di Clinical College of Tianjin Medical University, Tianjin 301800, China

Date of Web Publication29-Nov-2014

Correspondence Address:
Guangshun Wang
Department of Thoracic Surgery, Bao Di Hospital, Bao Di Clinical College of Tianjin Medical University, Tianjin 301800
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.145878

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 > Abstract 

Objective: The purpose of this retrospective study was to evaluate the clinical value of serum cytokeratin-19-fragment (cyfra21-1) as a biomarker in nonsmall cell lung cancer (NSCLC).
Methods: Sixty-six patients with NSCLC and 48 cases with benign lung disease were retrospectively analyzed in the department of thoracic surgery in our hospital. The serum level of cyfra21-1 was detected in the above patients. The diagnosis sensitivity, specificity and the receiver operating characteristic curve were calculated by using the stata11.0 statistical software to evaluate the clinical diagnosis value of serum Cyfra21-1 as NSCLC serologic biomarker.
Results: The mean of serum cyfra21-1 were 8.95 eat. 01 μ/L and 4.28 eat. 89 μ/L in NSCLC patient and control groups respectively, which indicated that the NSCLC group were much higher (P < 0.05). The diagnosis sensitivity and specificity were 77.08% and 63.64% at the threshold of 6.32 μ/L respectively. Moreover, the area under the curve was 0.78 (95% confidence interval: 0.70-0.87).
Conclusion: Serum cyfra21-1 can be a potential serologic biomarker in evaluation of NSCLC.

Keywords: Biomarker, cyfra21-1, diagnosis, nonsmall cell lung cancer


How to cite this article:
Zhao H, Shi X, Liu J, Chen Z, Wang G. Serum cyfra21-1 as a biomarker in patients with nonsmall cell lung cancer. J Can Res Ther 2014;10, Suppl S3:215-7

How to cite this URL:
Zhao H, Shi X, Liu J, Chen Z, Wang G. Serum cyfra21-1 as a biomarker in patients with nonsmall cell lung cancer. J Can Res Ther [serial online] 2014 [cited 2019 Dec 16];10:215-7. Available from: http://www.cancerjournal.net/text.asp?2014/10/7/215/145878

Hongjie Zhao and Xuejun Shi contribute equally to this work



 > Introduction Top


Lung cancer has been the leading cause of cancer-related death in the world-wide corresponding for 160 million new cases and 140 million deaths. [1] Moreover, the incidence rate for lung cancer is still on the rise in the developing countries such as China. [2] The main reason for the increasing incidence rate was cigarette smoking and air pollution [3] . About 75-80% lung cancer was nonsmall lung cancer and other 25-20% was small cell lung carcinoma. The NSCLC was the major pathology type of lung cancer. About 80% of NSCLC patients have advanced disease at diagnosis and thus lose the opportunity for surgery, which is the only chance for cure. Thus, early diagnosis of NSCLC can significant improve the prognosis of the lung cancer patients.

Clinical trials have proven that serum tumor biomarkers are over-expressed in patients with NSCLC such as carcino-embryonic antigen (CEA), cyfra21-1, neuron-specific enolase (NSE) and et al. [4] . Hence, we retrospectively analyzed the serum level of cyfra21-1 in patients with NSCLC and benign pulmonary disease in order to further evaluation the clinical diagnosis value of cyfra21-1 in NSCLC patients.


 > Materials and methods Top


0 Patients inclusion

Sixty-six patients with nonsmall cell lung cancer (NSCLC) and 48 cases with benign lung disease were retrospectively analyzed in the department of thoracic surgery in our hospital. The inclusion criteria for NSCLC were: The patients were more than 18-year-old; the pathology type were NSCLC with pathology or cytology confirmed; the serum cyfra21-1 could be extracted from the medical record of the NSCLC patients. The inclusion criteria for benign pulmonary disease: More than 18-year-old; with no evidence of cancers; with exact diagnosis of benign lung disease such as chronic obstructive pulmonary disease, pneumonia, pneumothorax and et al.

Cyfra21-1 array

A volume of 3-5 ml peripheral blood was extracted from the NSCLC and control patients. Sample was centrifuged and the supernatant was stored at −80°C until cyfra21-1 assay. Serum cyfra21-1 was assayed by commercial enzyme immunoassays kit. The procedure was according to the protocol.

Statistical analysis

The age, serum level of cyfra21-1 and other measurement data were demonstrated by mean ± standard deviation and compared by Student's t-test between the NSCLC and control groups. Receiver operating characteristic (ROC) curves were constructed using serum concentrations of cyfra21-1 of both NSCLC and control groups. Areas under the ROC curves (AUC) were calculated to determine the ability of each tumor marker to diagnose lung cancer. All the statistics are analyzed by Stata11.0 software (Stata Corporation, College Station, TX). A two tails P ≤ 0.05 was considered as statistical significance.


 > Results Top


0 General characteristic of included patients

Sixty-six NSCLC patients and 48 benign pulmonary disease patients were included in this study. Of the included 66 NSCLC patients, the mean age was 66.4 ± 11.2 years old with 41 (62.1%) male and 25 (37.9) female. All the then patients were pathology or cytology confirmed nonsmall lung cancer. The detail information was showed in [Table 1].
Table 1: The general characteristics of the patients with lung cancer


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Cyfra21-1 level in the two groups

The mean of serum cyfra21-1 were 8.95 eas. 01 μ/L and 4.28 e 4.89 μ/L in NSCLC patient and control groups respectively, which indicated that the NSCLC group were much higher (P < 0.05), demonstrated in [Figure 1].
Figure 1: The serum level of cyfra21-1 distribution in the two groups

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Diagnosis sensitivity and specificity

The diagnosis sensitivity and specificity were 77.08% (62.69-87.97%) and 63.64% (50.87-75.13%) at the threshold of 6.32 μ/L respectively.

Area under the receiver operating characteristic curve

The ROC was calculated by STATA11.0. The area under the ROC was 0.78 (95% confidence interval: 0.07-0.87) [Figure 2].
Figure 2: Receiver operating characteristic curve curve of nonsmall cell lung cancer versus benign lung diseases

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 > Discussion Top


Lung cancer is one of serious public health problem in the world. According to the epidemiological investigation, about 226,000 new cases and 160,000 deaths were found in the United States in the year of 2012 [1] . And only 16.0% patients with lung cancer can survive more than 5 years or more. Hence, lung cancer was considered as a hard nut to crack for doctors world-wide. [5]

Clinical studies indicated 80% of NSCLC patients have metastasis disease at the first diagnosis. And the only 20% patients have the opportunity for surgery that could prove an opportunity for cure. How to improve the early diagnosis for NSCLC is important for improving the prognosis. Biomarker array of cancers was believed to be an effective and convenient method for early detection of cancers. Several clinical studies have demonstrated that the serum CEA, NSE, cyfra21-1 and et al. are over-expressed in patients with early stage NSCLC, which indicated that the serum CEA, NSE, cyfra21-1 could be a potential serologic biomarker for NSCLC diagnosis. [6],[7] Several studies have showed that serum cyfra21-11 level patients with NSCLC was much higher than that in control groups. [4],[8] Cyfra21-1 is a major component of the cytoskeleton intermediate filaments of simple epithelium cells and is over expressed in various carcinomas including NSCLC. [9]

In this study, we retrospectively analyzed 66 cases with NSCLC and 48 subjects with benign lung diseases. The mean level of serum cyfra21-1 was 8.95 ± 6.01 μ/L with its range of 0.86-36.80 μ/L in NSCLC group. And in control group, the mean level of cyfra21-1 was 4.28 ± 4.89 μ/L with range of 0.14-30.37 μ/L. The mean serum level of cyfra21-1 in NSCLC group was significant higher than that in control group (P < 0.05). We use the ROC curve to further evaluate the clinical value of cyfra21-1 to diagnosis the NSCLC. The diagnosis sensitivity and specificity were 77.08% and 63.64% at the threshold of 6.32 μ/L respectively. And the AUC was 0.78 (95% confidence interval: 0.70-0.87). Recently, Song et al. [10] reported a prospective study about utility of cyfra21-1 in diagnosis lung cancer. In their study, 536 cases with lung cancer and 124 subjects with benign pulmonary disease were recruited. The mean serum concentrations of cyfra21-1 were 7.01 in squamous cell lung carcinoma which was a little bit lower than that in our study (8.95). And the diagnosis sensitivity and specificity were 23.3% and 95.4% at the cutoff of 4.0 μ/L reported by Song et al. and the diagnosis sensitivity reported was much lower than that in our study. The difference for the diagnosis sensitivity between the two study was maybe due to the different clinical stages, pathology types and different cut-off values.

In summary, serum cyfra21-1 was significant elevated in NSCLC patients. And combined with others screening methods, serum cyfra21-1 array can be a potential method for lung cancer diagnosis.

 
 > References Top

1.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 1
    
2.
Zeng H, Zheng R, Zhang S, Zou X, Chen W. Incidence and mortality of female breast cancer in China, 2009. Thorac Cancer 2013;4:400-4.  Back to cited text no. 2
    
3.
Karagueuzian HS, White C, Sayre J, Norman A. Cigarette smoke radioactivity and lung cancer risk. Nicotine Tob Res 2012;14:79-90.  Back to cited text no. 3
    
4.
Bates J, Rutherford R, Divilly M, Finn J, Grimes H, O'Muircheartaigh I, et al. Clinical value of CYFRA 21.1, carcinoembryonic antigen, neurone-specific enolase, tissue polypeptide specific antigen and tissue polypeptide antigen in the diagnosis of lung cancer. Eur Respir J 1997;10:2535-8.  Back to cited text no. 4
    
5.
Hsu NY, Lee H, Yen Y, Cheng YW. Human papillomavirus and non-small cell lung cancer. Thorac Cancer 2013;4:345-53.  Back to cited text no. 5
    
6.
Okamura K, Takayama K, Izumi M, Harada T, Furuyama K, Nakanishi Y. Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer. Lung Cancer 2013;80:45-9.  Back to cited text no. 6
    
7.
Pavicevic R, Bubanovic G, Franjevic A, Stancic-Rokotov D, Samarzija M. CYFRA 21-1 in non-small cell lung cancer - standardisation and application during diagnosis. Coll Antropol 2008;32:485-98.  Back to cited text no. 7
    
8.
Pang L, Wang J, Jiang Y, Chen L. Decreased levels of serum cytokeratin 19 fragment CYFRA 21-1 predict objective response to chemotherapy in patients with non-small cell lung cancer. Exp Ther Med 2013;6:355-60.  Back to cited text no. 8
    
9.
Kosacka M, Jankowska R. Comparison of cytokeratin 19 expression in tumor tissue and serum CYFRA 21-1 levels in non-small cell lung cancer. Pol Arch Med Wewn 2009;119:33-7.  Back to cited text no. 9
    
10.
Song WA, Liu X, Tian XD, Wang W, Liang CY, Zhang T, et al. Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: A prospective study from China. Chin Med J (Engl) 2011;124:3244-8.  Back to cited text no. 10
    


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