In recent years, with the deterioration of the environment and the aging of the population, the occurrence of various respiratory diseases is increasing. Lung cancer is a common respiratory malignant tumor that occurs in the bronchial mucosal epithelium and has become one of the main diseases endangering human life (11). Serum tumor markers are considered to be biological indicators detected from the serum or plasma of patients with suspicious tumors, which are used for early diagnosis, treatment monitoring, and prognostic evaluation(12). However, due to the insufficient sensitivity and specificity of tumor markers, the combined detection of multiple tumor markers has greater significance in tumor diagnosis (13).
CEA is a serum glycoprotein, which was first discovered by Gold and Freedman in gastrointestinal cancer cells in 1965 (14). A great number of studies have shown that the expression of CEA is elevated in patients with lung cancer, especially lung adenocarcinoma(15, 16). Our study showed that the positive rate and level of CEA were significantly higher in patients with lung cancer than in patients with benign lung diseases and healthy controls. However, there was no statistically significant difference in CEA levels among the three types of lung cancer (p>0.05).
CYFRA 21-1, a member of the keratin family, is a protein encoded by the KRT19 gene (17). Studies have shown that CYFRA21-1 is the most sensitive biomarker in NSCLC, especially for squamous cell carcinoma (18). Our results showed that the positive rate and level of CYFRA21-1 were significantly higher in patients with lung cancer than in those with benign lung diseases and healthy controls. We also found that the level of CYFRA21-1 in the lung squamous cell carcinoma group was higher than that in the lung adenocarcinoma and lung small cell carcinoma groups.
NSE, a form of glycolytic enolase isoenzyme, is considered to be a multifunctional protein (19). Serum NSE level is associated with melanoma (20), seminoma (21), renal cell carcinoma (22), immature teratoma (23) and malignant pheochromocytoma (24), particularly SCLC (25). Therefore, NSE is generally considered a diagnostic and therapeutic marker of SCLC(26). ProGRP is composed of three isoforms expressed at the mRNA level and is the neuropeptide gastrin-releasing peptide produced in SCLC cells (27). Besides, serum ProGRP elevations are specific to SCLCs, pulmonary carcinoid tumors, and several types of neuroendocrine tumors(28). Combined with NSE, proGRP plays an important role in the diagnosis of tumors and follow-up of small cell lung cancer (29). In this study, the positive rates and expression levels of serum NSE and proGRP in patients with lung cancer were significantly higher than those in patients with benign lung diseases and healthy controls. The levels of NSE and pro-GRP in the lung small cell carcinoma group were higher than those in the lung squamous cell carcinoma and lung adenocarcinoma groups, similar to the results reported by Cavalieri, S. et al. (30). In addition, our research showed that the diagnostic value of CYFARA21-1 combined with proGRP, NSE combined with proGRP, and the three indicators combined to detect small cell lung cancer was better than that of proGRP alone.
SCC-Ag is a tumor-associated protein used as a biomarker for a variety of human squamous cell carcinomas, including oral cancer (31), cervical cancer (32), esophageal cancer (33), and lung cancer (34). We found that the positive rate and level of SCC-Ag in patients with lung cancer were higher than those in patients with benign lung diseases and healthy controls, and the level of SCC-Ag in patients with squamous cell carcinoma was higher than in those with lung adenocarcinoma and lung squamous cell carcinoma; thus, SCC-Ag can be used as a diagnostic marker for lung squamous cell carcinoma.
This study analyzed the influence factors of lung cancer through an unconditional logistic regression model, and found that after quartiles, the higher the level of CEA, CYFRA21-1, NSE, and proGRP, the higher the incidence of lung cancer. This indicates that the levels of CEA, CYFARA21-1, NSE, and proGRP were linearly related to the occurrence of lung cancer, while the level of SCC-Ag was not significantly related to the occurrence of lung cancer. We then evaluated the diagnostic value of these four tumor markers alone and combined detection for lung cancer through the ROC curve, and found that the combined detection of CEA, CYFARA21-1, NSE, and proGRP had the highest diagnostic accuracy for lung cancer, and had certain practical value in clinical practice.
In addition to comprehensive diagnostic analysis of diagnostic markers, we also compared and analyzed the data of lung cancer survival and death groups. We found that the levels of CYFAR21-1 and NSE in the death group were higher than those in the survival group. At the same time, this study shows that the levels of CYFAR21-1 and NSE in patients with lung cancer are higher than those in patients with benign lung diseases and healthy controls. Therefore, it is obvious that CYFAR21-1 and NSE can be used to assess the prognosis of lung cancer patients and are regarded as indicators for predicting the prognosis of lung cancer patients.
In summary, tumor markers are important for the diagnosis of lung cancer. The combined detection of CEA, CYFARA21-1, NSE, and proGRP had the highest diagnostic accuracy for lung cancer. CYFAR21-1 and NSE can be used to evaluate the prognosis of lung cancer patients. Further research is required to identify new circulating biomarkers with sufficient specificity and sensitivity for clinical applications.