|Year : 2016 | Volume
| Issue : 1 | Page : 117-120
A retrospective analysis of serum tumor markers found in non-small cell lung cancer
Qin Hu1, Ping Xiao2, Junjie Li3, Pijun Yu3
1 Department of Radiotherapy, Jiangsu Cancer Hospital, Nanjing, China
2 Department of Cardio-Thoracic Surgery, Second Affiliated Hospital of Nantong University, Nantong, China
3 Department of Plastic Surgery, Eighth People's Hospital of Shanghai, Shanghai, China
|Date of Web Publication||13-Apr-2016|
Department of Plastic Surgery, The Eighth People's Hospital of Shanghai, 8 Caobao Road, Shanghai, 200235
Source of Support: None, Conflict of Interest: None
Aim: This paper discusses the retrospective analysis conducted to determine the significance of diagnostic biomarkers, carcinoembryonic antigens (CEA), cytokeratin fragment antigens 21-1 (CYFRA 21-1), neuron-specific enolases (NSE), and tumor-specific growth factors (TSGF) upon patients who suffered with non-small cell lung cancer (NSCLC).
Materials and Methods: From June 2010 to December 2011, we analyzed the positive rates of biomarkers in 276 NSCLC patients. We assessed the relationship between biomarkers and clinical characteristics of sex, smoking history, and disease stage.
Results: The median and positive rates of each serum biomarker were marked as 1.91–22.77 ng/ml and 35.86% (CEA), 2.0–6.77 ng/ml and 50% (CYFRA 21-1), 13.91–23.78 ng/ml and 62.31% (NSE), and 56–67 μ/ml and 10.14% (TSGF). The level of CEA in peripheral (2.43–23.76 ng/ml) was significantly higher than the level at central position (1.97–3.63 ng/ml) (P < 0.05).
Conclusion: Although the positive CEA, CYFRA 21-1, NSE, and TSGF rates were observed at low values during the NSLCLC serum diagnosis, they still played an important role in diagnosing lung cancer. Significant levels of CEA, CYFRA 21-1, NSE, and TSGF were detected in the serum. The amounts found were useful for diagnosing NSCLC patients who depended on the currently limited biomarker development.
Keywords: Carcinoembryonic antigen, cytokeratin fragment antigen 21-1, neuron-specific enolase, and tumor specific growth factor, non-small cell lung cancer, tumor biomarker
|How to cite this article:|
Hu Q, Xiao P, Li J, Yu P. A retrospective analysis of serum tumor markers found in non-small cell lung cancer. J Can Res Ther 2016;12:117-20
| > Introduction|| |
Non-small cell lung cancer (NSCLC) is the most frequent cause of cancer-related deaths in the world. Most patients are diagnosed in advanced stages and thus unable to receive surgical treatment. Therefore, it is necessary to determine effective biomarkers for early diagnosis of NSCLC. We analyzed clinical data of 276 patients who, in retrospect, suffered with histologically confirmed NSCLC. The biomarkers studied in this paper include: Carcinoembryonic antigens (CEA), cytokeratin fragment antigens 21-1 (CYFRA 21-1), neuron-specific enolases (NSE), and tumor-specific growth factors (TSGF).
| > Materials and Methods|| |
The Committee on Human Research of our hospital approved the following study. Patients, who were diagnosed with NSCLC, relied upon pathological reports where the levels of CEA, CYFRA 21-1, NSE, and TSGF in serum were collected. A total of 276 patients were enrolled in this study, all of whom ranged between the ages of 39 to 90 years (average, 66.47 ± 10.51 years). Of the 276 patients, 169 were men and 107 were women. Staging was based on the tumor, node, metastasis (TNM) classification system used by the International Union Against Cancer 2009(UICC) [Table 1]. The article does not involve personal privacy.
|Table 1: Classification and tumor, node, metastasis (TNM) staging of non-small cell lung cancer (NSCLC)|
Click here to view
We detected the CEA, CYFRA 21-1, NSE, and TSGF in the serum through Electrochemiluminescene immunoassay (ECLIA). The cut-off values found measured to 0–10 ng/ml (CEA), 0–3.3 ng/ml (CYFRA 21-1), 0–15.6 ng/ml (NSE), and 0–72 μ/ml (TSGF), respectively. Information regarding age, gender, smoke history, etc., was then obtained through an interviewer-administered questionnaire [Table 2].
|Table 2: Association between carcinoembryonic antigens, cytokeratin fragment antigens 21-1, neuron-specific enolases, tumor-specific growth factors and gender, history of smoking and clinical staging|
Click here to view
The data was analyzed by a statistical package of social sciences (SPSS) 17.0 software. The association between the level of biomarkers and the clinical pathological variables was statistically tested by a rank sum test, where P < 0.05 Bwas considered significant. The positive rate was completed by an X 2 Fisher's exact test and then tested by a Chi-square test.
| > Results|| |
- The levels and positive rates of tumor biomarkers in the serum developed from NSCLC patients, measured 1.91–22.77 ng/ml, 35.86% (CEA), 2.0–6.77 ng/ml and 50% (CYFRA 21-1), 13.91–23.78 ng/ml and 62.31% (NSE), 56–67μ/ml and 10.14% (TSGF), respectively. The positive rate of NSE was significantly higher than the rates of others [Table 3]
- There was no statistically significant difference between CEA, CYFRA 21-1, NSE, and TSGF in regards to gender, smoking history, and tumor stages [Table 2]
- The level of CEA in the peripheral type (2.43–23.76 ng/ml) was higher than that in the central type (1.97–3.63 ng/ml). There was no statistically significance to the values CEA, CYFRA 21-1, NSE, and TSGF. These markers also showed no difference in tumor size, history, differentiation, lymph node metastasis, or clinical stage [Table 4].
|Table 3: Median and positive rates of carcinoembryonic antigens, cytokeratin fragment antigens 21-1, neuron-specific enolases, and tumor-specific growth factors|
Click here to view
|Table 4: The relationship between carcinoembryonic antigens, cytokeratin fragment antigens 21-1, neuron-specific enolases, and tumor-specific growth factors markers and pathological characteristics|
Click here to view
| > Discussion|| |
In comparison to a single tumor marker, the detection of CYFRA 21-1, NSE, and TSGF markers in the serum, can significantly improve sensitivity to detecting NSCLC. Despite low positive rates and insufficient specificity for determining tumor types and locations, as they, these biomarkers are useful and significant in conducting primary diagnosis, monitoring recurrence, or following up treatments. Molina founded that the positive rates of CEA, NSE, and CYFRA in lung cancer patients, respectively, measured to 6.6%, 0.7%, and 8.7%. The higher positive rates were however measured at CEA (35.93%), CYFRA 21-1 (50%), NSE (62.5%), and TSGF (10.93%). The positive rates are close associated with the advanced stages of the study. Pachuca illustrated that the positive rates of CEA (> ng/mL, range: 5–7, 440 ng/mL) in 182 cases (total 270 cases), the value of CEA levels significantly decreased in the serum of the patients who underwent chemotherapy treatment. These findings confirmed the diagnostic role of CEA. The findings also emphasized its significance during disease assessment, following chemotherapy procedures.
The level of CEA in the tested serum is a vital prognostic marker, where negative results will determine a 5-years survival rate. If the value of CEA remained high after stage I lung cancer operations, a poor prognosis will be determined. CYFRA 21-1 is an effective biomarker for the diagnosis of NSCLC., It contributes to primary diagnosis, where the prognosis is a useful biomarker for patients requiring a follow-up after surgery or chemotherapy , and radiotherapy. Expressions of the NSE level is up-regulated in both nerve and lung cancerous tissues. Because it is negatively associated with the survival rate, it has the potential to be an useful marker for the diagnosis and prognosis of NSCLC.
The sensitivity of CEA for diagnosing NSCLC can be improved by CYFRA 21-1, Pujol  assessed the relationship between tumor prognostic biomarkers such as CYFRA 21-1, CEA, and NSE and the survival rates of 515 NSCLC patients, and suggested that CYFRA 21-1 and CEA play a negative role in potential survival for patients administered into surgery. CYFRA21-1 contributes sensitivity and accuracy (60.0% and 70.3%, respectively) in diagnosing for lung cancer, while providing extreme sensitivity (79.6%) in diagnosing for squamous carcinoma. CEA experiences extreme sensitivity (75.7%) in diagnosing for adenocarcinoma. It is also experiences significant sensitivity and accuracy at: 60.0% and 70.3%, respectively. Combined detection of CYFRA 21-1, CEA, and NSE in the serum can improve in sensitivity and specificity (82.9% and 83.4%.) when diagnosing NSCLC. NSE revealed especially significant sensitivity (76.2%) for diagnosing small cell lung cancer. Lazarev evaluated the levels of CEA, CYFRA 21-1, and NSE in serum collected from 739 NSCLC patients. The resulting analysis confirmed that these tumor biomarkers played an unnecessary role in diagnosing lung cancer of low sensitivity. Meanwhile, due to affordable and simple clinical practices, these biomarkers can be used to conduct primary diagnosis on NSCLC patients.
In our study, the median and positive rates of each serum biomarker measured to 1.91–22.77 ng/ml and 35.86% (CEA), 2.0–6.77 ng/ml and 50% (CYFRA 21-1), 13.91–23.78 ng/ml and 62.31% (NSE), and 56–67μ/ml and 10.14% (TSGF), respectively. The level of CEA in the peripheral areas (2.43–23.76 ng/ml) was significantly higher than the levels found in the central area (1.97–3.63 ng/ml) (P < 0.05). The positive rates of NSE were significantly higher than the rates of the other biomarkers.
Ultimately, although the positive rates of CEA, CYFRA 21-1, NSE, and TSGF for diagnosing NSLCLC in the serum were low, lacking in specificity of tumor locations, they still play a key role in diagnosing lung cancer. Depending on the (currently limited) biomarkers development, further research is necessary to determine the specificity and sensitivity of biomarkers. The study illustrated that although positive rates were low, they are useful and significant in diagnosing for NSCLC.
| > Conclusion|| |
The study illustrated that although positive rates were low, they are useful and significant in diagnosing for NSCLC.
| > Acknowledgment|| |
We thanked Qin Hu, Ping Xiao, Junjie Li and Pijun Yu who major responsible for data collection, statistic analysis.
| > References|| |
Molina R, Auge JM, Escudero JM, Marrades R, Viñolas N, Carcereny E, et al
. Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: Comparison with CYFRA 21-1, CEA, SCC and NSE. Tumour Biol 2008;29:371-80.
D Pachuca O, Peña M, Morales A. Usefulness of monitoring serum carcinoembryonic antigen (CEA) to define response to chemotherapy and its correlation with survival in patients with non-small cell lung cancer with abnormal baseline CEA levels. J Clin Oncol 2010;e18044.
Tomita M, Shimizu T, Ayabe T, Yonei A, Onitsuka T. Carcinoembryonic antigen level in serum and pleural lavage fluid in non-small cell lung cancer. Thorac Cardiovasc Surg 2010;58:350-3.
Wang CY, Huang MS, Huang MH, Lee HC, Hsu HS. Persistently high serum carcinoembryonic antigen levels after surgery indicate poor prognosis in patients with stage I non-small-cell lung cancer. J Surg Res 2010;163:e45-50.
Farlow EC, Vercillo MS, Coon JS, Basu S, Kin AW, Faber LP, et al
. A multi-analyte serum test for the detection of non-small cell lung cancer. Br J Cancer 2010;103:1221-8.
Tomita M, Shimizu T, Ayabe T, Yonei A, Onitsuka T. Prognostic significance of tumour marker index based on preoperative CEA and CYFRA 21-1 in non-small cell lung cancer. Anticancer Res 2010;30:3099-102.
Muley T, Dienemann H, Ebert W. Increased CYFRA 21-1 and CEA levels are negative predictors of outcome in p-stage I NSCLC. Anticancer Res 2003;23:4085-93.
Wang J, Yi Y, Li B, Wang Z, Sun H, Zhang P, et al
. CYFRA21-1 can predict the sensitivity to chemoradiotherapy of non-small-cell lung carcinoma. Biomarkers 2010;15:594-601.
Ferrigno D, Buccheri G, Giordano C. Neuron-specific enolase is an effective tumour marker in non-small cell lung cancer (NSCLC). Lung Cancer 2003;41:311-20.
Patel JL, Erickson JA, Roberts WL, Grenache DG. Performance characteristics of an automated assay for the quantitation of CYFRA 21-1 in human serum. Clin Biochem 2010;43:1449-52.
Pujol JL, Boher JM, Grenier J, Quantin X. Cyfra 21-1, neuron specific enolase and prognosis of non-small cell lung cancer: Prospective study in 621 patients. Lung Cancer 2001;31:221-31.
Hirose T, Okuda K, Yamaoka T, Ishida K, Kusumoto S, Sugiyama T, et al.
Are levels of pro-gastrin-releasing peptide or neuron-specific enolase at relapse prognostic factors after relapse in patients with small-cell lung cancer? Lung Cancer 2011;71:224-8.
Lazarev SM, Massard ZH, Reshetov AV, Nikolaev GV, Volgin GN, Osipov EV, et al
. Role of biological tumor markers CEA, Cyfra-21, NSE, TU M2-PK in diagnosis and treatment of lung cancer. Vestn Khir Im I I Grek 2010;169:39-43.
Hansen O, Sorensen P, Hansen KH. The occurrence of hyponatremia in SCLC and the influence on prognosis: A retrospective study of 453 patients treated in a single institution in a 10-year period. Lung Cancer 2010;68:111-4.
[Table 1], [Table 2], [Table 3], [Table 4]