Assessment of circulating biomarkers for detection of lung cancer in a high-risk cohort.

BACKGROUND: There is an urgent need for early detection of lung cancer. Screening with low-dose computed tomography (LDCT) is now implemented in the US. Supplementary use of a lung cancer biomarker with high specificity is desirable. OBJECTIVE: To assess the diagnostic properties of a biomarker panel consisting of cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125). METHODS: A cohort of 250 high-risk patients was investigated on suspicion of lung cancer. Ahead of diagnostic work-up, blood samples taken. Cross-validated prediction models were computed to assess lung cancer detection properties. RESULTS: In total 32% (79/250) of patients were diagnosed with lung cancer. Area under the curve (AUC) for the three biomarkers was of 0.795, with sensitivity/specificity of 57%/93% and negative predictive value of 83%. When combining the biomarkers with US screening criteria, the AUC was 0.809, while applying only US screening criteria on the cohort, yielded an AUC of 0.62. The ability of the biomarkers to detect stage I-II lung cancer was substantially lower; AUC 0.54. CONCLUSIONS: In a high-risk cohort, the detection properties of the three biomarkers were acceptable compared to current LDCT screening criteria. However, the ability to detect early stage lung cancer was low.

Three tumor markers for improved efficacy in the management of patients with malignant pleural mesothelioma.

BACKGROUND: Evaluation of tumor markers may facilitate follow-up of malignant pleural mesothelioma (MPM). We aimed was to evaluate the value of tumor markers for monitoring and predicting recurrence in patients with MPM. METHODS: In total, 152 patients who underwent curative-intent surgery after induction chemotherapy for MPM between July 2004 and December 2017 were retrospectively reviewed. Preoperative and postoperative (≤3 months after surgery) levels of soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (Cyfra21-1), and tissue polypeptide antigen (TPA) and rates of recurrence and non-recurrence were evaluated. Factors associated with recurrence-free survival (RFS) were assessed using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: Of the 152 patients, the positive rates of preoperative SMRP, Cyfra21-1, and TPA, levels were 26.7%, 8.6%, 9.6%, respectively; the respective postoperative levels were 4.0%, 6.3%, and 6.5%; the respective levels in patients with recurrence were 39.3%, 31.4%, 28.6%; the respective levels in patients with no recurrence were 3.7%, 0.0%, 3.8%. Nearly half (45.2%) of the patients with recurrence exhibited an increase in one or more tumor marker levels. Multivariate analysis revealed that the preoperative positive rates of one or more of the three tumor markers (hazard ratio: 1.8, 95% confidence interval: 1.1-2.8; P=0.02) were independent significant predictors of recurrence. CONCLUSIONS: The positive rates of SMRP, Cyfra21-1, and TPA in recurrence-free patients were extremely low, with high specificity. Preoperative levels of SMRP, Cyfra21-1, and TPA, which identified patients with a high risk for recurrence, could improve management of patients with MPM.

High-Sensitivity Detection of the Lung Cancer Biomarker CYFRA21-1 in Serum Samples Using a Carboxyl-MoS2 Functional Film for SPR-Based Immunosensors.

We constructed a novel surface plasmon resonance (SPR) detection assay using carboxyl-functionalized molybdenum disulfide (carboxyl-MoS2) nanocomposites as a signal amplification sensing film for the ultrasensitive detection of the lung cancer-associated biomarker cytokeratin 19 fragment (CYFRA21-1). The experiment succeeded in MoS2 reacted with chloroacetic acid giving carboxyl-MoS2 as the reaction product. The additional shoulder in the C 1s and O 1s peaks of carboxyl-MoS2, which were increased in X-ray photoelectron spectroscopy, confirmed the presence of O-C=O groups on the surface of the carboxyl-MoS2. Compared to MoS2, the experimental results confirmed that carboxyl-modified MoS2 had improved low impedance and low refractive index. The carboxyl-MoS2-based chip had a high affinity, with an SPR angle shift enhanced by 2.6-fold and affinity binding K A enhanced by 15-fold compared to a traditional SPR sensor. The results revealed that the carboxyl-MoS2-based chip had high sensitivity, specificity, and SPR signal affinity, while the CYFRA21-1 assay in spiked clinical serum showed a lower detection limit of 0.05 pg/mL and a wider quantitation range (0.05 pg/mL to 100 ng/mL). The carboxyl-MoS2-based chip detection value was about 104 times more sensitive than the limit of detection of an enzyme-linked immunosorbent assay (ELISA) (0.60 ng/mL). The results showed that the carboxyl-MoS2-based chip had the potential to rapidly assay complex samples including bodily fluids, whole blood, serum, plasma, urine, and saliva in SPR-based immunosensors to diagnose diseases including cancer.

Screening values of carcinoembryonic antigen and cytokeratin 19 fragment for lung cancer in combination with low-dose computed tomography in high-risk populations: Initial and 2-year screening outcomes.

OBJECTIVES: To assess added screening value of Carcinoembryonic Antigen (CEA) and Cytokeratin 19 Fragment (CYFRA 21-1) in combination with LDCT beyond LDCT alone and likelihood ratio of positive (LHR+) of their combination for lung cancer in high-risk populations with indeterminate and positive LDCT after initial screening and 2-year follow up. MATERIALS AND METHODS: LDCT was performed annually at baseline and for 2 years in 634 heavy smokers (>30 pack-years) who were aged 50-70 years, and it was classified as negative, indeterminate, or positive (suspicious for lung cancer). Serum CEA and CYFRA 21-1 were examined and followed with LDCT in the indeterminate and positive LDCT groups and defined as positive with an abnormal level of either CEA or CYFRA 21-1. RESULTS: A total of 17 lung cancer cases were diagnosed (9 from initial screening and 8 from follow-up cycles). Seventy and 22 patients had indeterminate and positive baseline LDCT, respectively. Among indeterminate baseline LDCT, the LHR+ for lung cancer diagnosed after initial screening with a positive marker was 6.61 (p = .039) and 1.51 (p = .502) with a negative marker. After 2 years follow up, the LHR+ was 6.31 (p = .004) and 0.86 (p = .677), respectively. Among positive baseline LDCT, the LHR+ for lung cancer diagnosed after initial round with positive and negative markers was 69.44 (p < 0.001) and 11.57 (p = .015), respectively. The corresponding LHR+ after 2-year round was 13.61 (p = .002) and 18.15 (p = .001), respectively. The combinations of CEA/CYFRA 21-1 and LDCT, and CEA and LDCT had crude and adjusted added value beyond LDCT alone (crude: 8%, p = .033 and 7%, p = .038; adjusted: 4%, p = .019 and 4%, p = .029, respectively). CONCLUSIONS: CEA in combination with LDCT significantly increases the value of lung cancer screening compared with using LDCT alone particularly in participants with indeterminate baseline LDCT in both initial and 2-year screening outcomes.

Systematic review of CYFRA 21-1 as a prognostic indicator and its predictive correlation with clinicopathological features in Non-small Cell Lung Cancer: A meta-analysis.

AIM: To evaluate the value of Cytokeratin 19 fragment for its survival prognostic indicator and predictive correlation with clinicopathological features in Non-small Cell Lung Cancer. METHODS: Eligible studies or databases for articles were retrieved via search systematically. Pooled effect was calculated to evaluate the association between Cytokeratin 19 fragment level and long-term overall survival, as well as the tumor clinicopathological features in Non-small Cell Lung Cancer patients. A fixed-effects or random-effects model was used to calculate the Pooled risk ratios (RRs) and corresponding 95 % confidence intervals (CIs). RESULTS: Six studies were up to the selection criteria. This meta-analysis indicated that Cytokeratin 19 fragment high level expression correlated with lower 2-year overall survival (RR =0.47; 95%CI: 0.28-0.79), higher Tumor Node Metastasis stage (II+III+IV) (RR =1.43; 95%CI: 1.15-1.76) in Non-small Cell Lung Cancer. The pooled RR estimates indicated that there is no statistical significance of Cytokeratin 19 fragment level expression in the advanced Non-small Cell Lung Cancer (IIIB+IV) (RR =1.43, 95% CI: 0.85-2.43). CONCLUSION: Cytokeratin 19 fragment is a negative prognosis indicator and its high level expression indicates higher Tumor Node Metastasis pathological stage (II+III+IV) in Non-small Cell Lung Cancer. In advanced Non-small Cell Lung Cancer, the level of serum Cytokeratin 19 fragment appears to provide more prognostic information than it does for clinical Tumor Node Metastasis stage information. Further studies are required to confirm our results.

Decreased levels of serum cytokeratin 19 fragment CYFRA 21-1 predict objective response to chemotherapy in patients with non-small cell lung cancer.

Diagnostic tools capable of predicting early responses to chemotherapy are required to improve the individual management of cancer patients. The present study aimed to evaluate the prognostic significance of the serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen (CA) 125, and CA 19-9 for predicting responses to different chemotherapy regimens in patients with non-small cell lung cancer (NSCLC). A total of 276 patients with postoperative stage I-IV NSCLC were retrospectively reviewed. The five tumor markers were measured before and after at least two cycles of chemotherapy using an electrochemiluminescent assay. Multivariate analysis revealed that performance status, age, postoperative stage and surgery were significantly associated with the response to chemotherapy. High baseline CYFRA 21-1 and CA 19-9 levels were associated with poor effectiveness of chemotherapy. Significant reductions in CYFRA 21-1 levels were associated with a positive response to various chemotherapy regimens. CEA, CA 125 and CA 19-9 expression was only associated with a positive response in patients receiving paclitaxel, docetaxel, pemetrexed and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). NSE expression was only associated with a positive response to gemcitabine. Receiver operating characteristic (ROC) curve analysis indicated that CYFRA 21-1 is the most sensitive of the tumor markers in predicting the response to chemotherapy. Serum CYFRA 21-1 is a useful surrogate marker for predicting the response to different chemotherapy regimens used to treat NSCLC and is a more sensitive marker than CEA, CA125, CA19-9 and NSE.

Pathologic correlation of serum carcinoembryonic antigen and cytokeratin 19 fragment in resected nonsmall cell lung cancer.

BACKGROUND: This study focused on the association between preoperative serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (Cyfra 21-1) levels and pathologic parameters in patients with resected non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The records of 527 patients who underwent pulmonary resection of NSCLC were reviewed. The association between preoperative serum CEA and Cyfra 21-1 levels and variables that had p-values of less than 0.05 in a t-test or one-way analyses of variance was analyzed by multiple linear regression. RESULTS: The mean serum CEA and Cyfra 21-1 levels prior to surgery were 6.8±23.1 mg/dL (range, 0.01 to 390.8 mg/dL) and 5.4±12.3 mg/dL (range, 0.65 to 140.2 mg/dL). The serum CEA levels were associated with tumor (T) and lymph node (N) stage and histology. The serum Cyfra 21-1 levels were associated with T stage, tumor size, and histology. Multiple linear regression indicated that serum CEA levels were associated with T (T3/4 vs. T1: ß=8.463, p=0.010) and N stage (N2/3 vs. N0: ß=9.208, p<0.001) and histology (adenocarcinoma vs. squamous cell: ß=6.838, p=0.001), and serum Cyfra 21-1 levels were associated with tumor size (ß=2.579, p<0.001) and histology (squamous cell vs. adenocarcinoma: ß=4.420, p=0.020). CONCLUSION: Serum CEA level was correlated with T and N stage, and Cyfra 21-1 with tumor size. CEA and Cyfra 21-1 showed histologic correlation. CEA is mainly elevated in adenocarcinoma and Cyfra 21-1 in squamous cell carcinoma. These results might be helpful for predicting pathologic status in preoperative NSCLC.

Pathologic Correlation of Serum Carcinoembryonic Antigen and Cytokeratin 19 Fragment in Resected Nonsmall Cell Lung Cancer

BACKGROUND: This study focused on the association between preoperative serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (Cyfra 21-1) levels and pathologic parameters in patients with resected non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The records of 527 patients who underwent pulmonary resection of NSCLC were reviewed. The association between preoperative serum CEA and Cyfra 21-1 levels and variables that had p-values of less than 0.05 in a t-test or one-way analyses of variance was analyzed by multiple linear regression. RESULTS: The mean serum CEA and Cyfra 21-1 levels prior to surgery were 6.8+/-23.1 mg/dL (range, 0.01 to 390.8 mg/dL) and 5.4+/-12.3 mg/dL (range, 0.65 to 140.2 mg/dL). The serum CEA levels were associated with tumor (T) and lymph node (N) stage and histology. The serum Cyfra 21-1 levels were associated with T stage, tumor size, and histology. Multiple linear regression indicated that serum CEA levels were associated with T (T3/4 vs. T1: beta=8.463, p=0.010) and N stage (N2/3 vs. N0: beta=9.208, p<0.001) and histology (adenocarcinoma vs. squamous cell: beta=6.838, p=0.001), and serum Cyfra 21-1 levels were associated with tumor size (beta=2.579, p<0.001) and histology (squamous cell vs. adenocarcinoma: beta=4.420, p=0.020). CONCLUSION: Serum CEA level was correlated with T and N stage, and Cyfra 21-1 with tumor size. CEA and Cyfra 21-1 showed histologic correlation. CEA is mainly elevated in adenocarcinoma and Cyfra 21-1 in squamous cell carcinoma. These results might be helpful for predicting pathologic status in preoperative NSCLC.

Pathologic Correlation of Serum Carcinoembryonic Antigen and Cytokeratin 19 Fragment in Resected Nonsmall Cell Lung Cancer

BACKGROUND: This study focused on the association between preoperative serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (Cyfra 21-1) levels and pathologic parameters in patients with resected non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The records of 527 patients who underwent pulmonary resection of NSCLC were reviewed. The association between preoperative serum CEA and Cyfra 21-1 levels and variables that had p-values of less than 0.05 in a t-test or one-way analyses of variance was analyzed by multiple linear regression. RESULTS: The mean serum CEA and Cyfra 21-1 levels prior to surgery were 6.8+/-23.1 mg/dL (range, 0.01 to 390.8 mg/dL) and 5.4+/-12.3 mg/dL (range, 0.65 to 140.2 mg/dL). The serum CEA levels were associated with tumor (T) and lymph node (N) stage and histology. The serum Cyfra 21-1 levels were associated with T stage, tumor size, and histology. Multiple linear regression indicated that serum CEA levels were associated with T (T3/4 vs. T1: beta=8.463, p=0.010) and N stage (N2/3 vs. N0: beta=9.208, p<0.001) and histology (adenocarcinoma vs. squamous cell: beta=6.838, p=0.001), and serum Cyfra 21-1 levels were associated with tumor size (beta=2.579, p<0.001) and histology (squamous cell vs. adenocarcinoma: beta=4.420, p=0.020). CONCLUSION: Serum CEA level was correlated with T and N stage, and Cyfra 21-1 with tumor size. CEA and Cyfra 21-1 showed histologic correlation. CEA is mainly elevated in adenocarcinoma and Cyfra 21-1 in squamous cell carcinoma. These results might be helpful for predicting pathologic status in preoperative NSCLC.