Serum CYFRA Research Articles

Detecting Lung Cancer Stages Earlier By Appropriate Markers Rather Than Biopsy And Other Techniques

Abstract Introduction/Objective Early detection of lung cancer stages is deeply under consideration of scientists. By day, high rate of mortality might be caused by cancer of lung over the world. The biopsy is still the golden standard as a histological predictor to determine lung cancer worldwide. However, a biopsy has various complications and hardness especially in collecting tissue samples. Therefore, detecting appropriate tools to determine the early stages of lung cancer is urgently needed. Some biomarkers levels have been determined in patient’s serum. The correlation between studied biomarkers and lung cancer has been studied by current research to avoid biopsy and other techniques. Methods The various biomarkers such as (CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4) were measured and calculated in 379 infected cases with lung cancer. Also, the same parameters were determined in 113 healthy persons as controls. Alternative markers’ levels were determined by using ELISA technique. Noninvasive markers were approved by comparison with CT chest scan and Biopsy techniques. Results Our research has indicated that Some of the studied biomarkers such as cytoskeleton-associated protein 4 (CKAP4), pro-gastrin-releasing peptide (ProGRP) and Prolactin (PRL) have high sensitivity from 77.05% to 96.72% and accuracy from 89.71% to 97.79% as well as their cut off which approved the aim of this study. However, other indicators (CEA, SCCA and CYFRA21-1) have low sensitivity from 62.49 % to 87.31% and accuracy between 71.27 % and 88.43 %. Meanwhile, CT scan has high sensitivity around 83% with specificity about 71%. Conclusion Alternative biomarkers (CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4) are considered as prospective markers to differentiate healthy individuals from lung cancer disease by their significant results in early stages detection. Thence, if serum CEA, SCCA, CYFRA21-1, ProGRP, Prolactin and CKAP4 are measured together, it would be the precise criterion of early levels of lung cancer rather than the lung biopsy definitely. However, further researches are needed to prove more reliable noninvasive markers of lung cancer.

Prognostic significance of pre-treatment serum Cyfra21-1 as a tumor marker in patients with oropharyngeal squamous cell carcinoma treated with concurrent chemoradiotherapy.

BackgroundOropharyngeal squamous cell carcinoma (OPSCC) is a kind of squamous cell carcinoma of head and neck, and its incidence is on the rise in recent years. A variety of prognostic markers for OPSCC have been reported in many studies, but they are expensive or difficult to obtain. So, we retrospectively studied the prognostic significance of cytokeratin 19 soluble fragment (Cyfra21-1) in patients with OPSCC, in order to provide theoretical basis for accurate prognosis assessment.MethodsA retrospective analysis of the clinicopathological data of 85 OPSCC patients with concurrent radiotherapy and chemotherapy (CRT) admitted from January 2010 to June 2017. Serum Cyfra21-1 levels were measured before treatment. Analyze the relationship between Cyfra21-1 and clinical pathological characteristics of patients. The receiver operating characteristic (ROC) curve was used to calculate the cut-off value of Cyfra21-1. The Cox proportional hazard model was used to conduct univariate and multivariate analysis of related prognostic factors, and to determine the factors related to overall survival (OS) and progression-free survival (PFS).ResultsThe cutoff value for Cyfra21-1 was 2.93 ng/mL. The baseline data of patients in different Cyfra21-1 groups were balanced and comparable. In the univariate and multivariate analyses, it was found that Cyfra21-1 was associated with OS and PFS. A measurement of Cyfra21-1 ≥2.93 ng/mL indicated poor OS (P<0.001) and PFS (P=0.001). After adjusting for age and disease stage, Cyfra21-1 can independently affect the OS (HR =3.57, 95% CI: 1.60–7.99, P=0.002) and PFS (HR =2.89, 95% CI: 1.41–5.91, P=0.004) of patients with OPSCC treated with CRT.ConclusionsPre-treatment Cyfra21-1 can be used as a prognostic marker for patients with OPSCC treated with CRT, which has important clinical significance.

Advanced pneumonic type of lung adenocarcinoma: survival predictors and treatment efficacy of the tumor

To retrospectively explore the survival predictors and treatment efficacy of advanced pneumonic-type lung adenocarcinoma (P-ADC). Retrospective analysis of clinical data and survival follow-up was undertaken on 41 patients with advanced P-ADC from January 1, 2009, to April 30, 2019. Analysis on tumor biomarkers such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and the cytokeratin-19-fragment (Cyfra21-1) were undertaken. The patients in this study were divided into three groups based on usage of tyrosine kinase inhibitor (TKI): TKI therapy group (including combination with chemotherapy), non-TKI therapy group (chemotherapy alone), and palliative care group. More than half of the patients had higher levels of tumor biomarkers and the incidence of NSE was highest (81.8%), followed by CEA (74.4%) and Cyfra21-1 (74.1%). All patients had abnormal findings on chest computed tomography and with adenocarcinoma pathology. The overall survival (OS) time was 10.4 months in TKI group, 8.8 months in the non-TKI group, and 2.1 months in the palliative care group. Patients with higher level of serum Cyfra21-1 had insignificantly shorter survival time compared to those with normal Cyfra21-1 (p = 0.067). TKI therapy and non-TKI therapy provided a better prognosis prediction compared to palliative care. TKI therapy improved prognosis compared to non-TKI therapy. The comprehensive based TKI therapy provided improved OS vs the non-TKI therapy. TKI-based therapy could improve the prognosis and OS for advanced P-ADC. This study recommends the analysis of EGFR mutations for all patients with advanced P-ADC.

Long intergenic noncoding RNA LINC00173 as a potential serum biomarker for diagnosis of non-small-cell lung cancer.

Long intergenic non-coding RNA (lincRNA) belongs to a special type of RNA that is unable to encode proteins but has been proved to play a role in gene regulation and differentially expressed in various malignant tumors. In this study, we aimed to identify whether lincRNA LINC00173 was differentially expressed in non-small-cell lung cancer (NSCLC) and whether it could serve as a potential diagnostic biomarker. The quantification real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00173 in serum and cultured cells. For large sample analysis, the lncRNA expression matrix in TCGA database were generated via R software. To evaluate the diagnostic performance of serum LINC00173, the receiver operating characteristic (ROC) curve was used. The qRT-PCR analysis showed that the serum LINC00173 expression level in 108 NSCLC patients was higher than that in 91 healthy donors and 55 patients with benign pulmonary disease (BPD). And the area under the curve (AUC) of serum LINC00173 was 0.809 for the diagnosis of NSCLC (95% CI: 0.750-0.868, p< 0.001), 0.670 for BPD (95% CI: 0.584-0.756, P< 0.001), and 0.730 for small-cell lung cancer (SCLC, 95% CI: 0.636-0.825, P< 0.001). Besides, we established a diagnostic model of combined detection of LINC00173, CEA and Cyfra21-1, and found that combined detection of these indicators significantly improved the diagnostic efficiency. Analysis of the Clinicopathological parameters showed that high LINC00173 expression was correlated with histological typing of tumor, tumor metastasis and serum Cyfra21-1 levels. In addition, serum LINC00173 expression decreased in patients who received chemotherapy and rebound in recurrent NSCLC patients. Serum LINC00173 may prove to be a potential non-invasive auxiliary diagnostic biomarker for NSCLC patients.

Dynamics of Serum Tumor Markers Can Serve as a Prognostic Biomarker for Chinese Advanced Non-small Cell Lung Cancer Patients Treated With Immune Checkpoint Inhibitors.

Background: Serum tumor markers carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cytokeratin 19 fragment (CYFRA21-1) and squamous-cell carcinoma-related antigen (SCC-Ag) are routinely used for monitoring the response to chemotherapy or targeted therapy in advanced-stage non-small cell lung cancer (NSCLC), however their role in immunotherapy remains unclear. The aim of this study was to investigate whether dynamics of these serum markers were associated with the efficacy and prognosis of Chinese late-stage NSCLC patients treated with programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors.Methods: We initiated a longitudinal prospective study on advanced NSCLC patients treated with PD-1/PD-L1 inhibitors in Chinese PLA general hospital (Beijing, China). Blood samples of baseline and after 6 weeks' treatment were collected. CT scan were used by all patients to evaluate treatment efficacy according to RECIST 1.1. Serum tumor markers levels were measured with an electrochemical luminescence for SCC-Ag and with a chemiluminescent microparticle immunoassay for serum CEA, CA125, and CYFRA21-1. At least 20% decreases of the biomarkers from baseline were considered as meaningful improvements after 6 weeks of treatment with immune checkpoint inhibitors (ICIs). Optimization-based method was used to balance baseline covariates between different groups. Associations between serum tumor biomarker improvements and objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were analyzed.Results: A total of 308 Chinese patients with advanced NSCLC were enrolled in the study. After balancing baseline covariates, patients with meaningful improvements in <2 out of 4 biomarkers (CEA, CA125, CYFRA21-1, and SCC-Ag) was ended up with lower ORR (0.08 vs. 0.35, p < 0.001), shorten PFS (median: 5.4 vs. 12.5 months, p < 0.001), and OS (median: 11.7 vs. 25.6 months, p < 0.001) in the total population. Subgroup analysis of patients with adenocarcinoma revealed that patients with meaningful improvements in <2 out of 4 biomarkers had significant lower ORR (0.06 vs. 0.36, p < 0.001), shorten PFS (median: 4.1 vs. 11.9 months, p < 0.001), and OS (median: 11.9 vs. 24.2 months, p < 0.001). So as in patients with squamous cell carcinoma, meaningful improvements in at least 2 out of 4 biomarkers were linked to better ORR (0.42 vs. 0.08, p = 0.014), longer PFS (median: 13.1 vs. 5.6 months, p = 0.001), and OS (median: 25.6 vs. 10.9 months, p = 0.06).Conclusions: The dynamic change of CEA, CA125, CYFRA21-1, and SCC-Ag from baseline have prognostic value for late-stage NSCLC patients treated with PD-1/PD-L1 inhibitors. Decrease of associated biomarkers serum levels were associated with favorable clinical outcomes.

Prediction of Pleural Invasion in Challenging Non-Small-Cell Lung Cancer Patients Using Serum and Imaging Markers.

Introduction. Preoperative detection of pleural invasion in lung cancer patients is key to curative surgical treatment. We tried to predict pleural invasion in non-small-cell lung cancer patients with <100 ml pleural fluid. Methods Patients admitted from August 1, 2011, to December 31, 2018, were retrospectively retrieved. Records of serum and imaging markers were analyzed. Results Among 7004 patients who received surgery, 43 cases with <100 ml pleural fluid who had pleural invasion were included, and another 108 cases without pleural invasion were enrolled as controls. There were no differences in squamous cell carcinoma antigen (SCC) or neuron-specific enolase (NSE) values between the pleural invasion and noninvasion groups (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (p = 0.30 and 0.14, respectively), but there were significant differences in carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) values (Conclusions Serum CEA and CYFRA21-1, location of original lung cancer (right mid lobe), maximum diameter, CT-detectable pleural fluid, pleural sign by CT, and PET/CT-predicted pleural invasion were good markers for the prediction of pleural invasion in non-small-cell lung cancer patients.

A surgical case of pulmonary actinomycosis with elevated serum CYFRA21-1 levels

A surgical case of pulmonary actinomycosis with elevated serum CYFRA21-1 levels

Expression and Clinical Significance of miR-152 and CYFRA21-1 in Ovarian Cancer Tissues

To investigate the expression and clinical significance of miR-152 and CYFRA21-1 in ovarian cancer (OC) tissues. Seventy-four OC patients diagnosed in our hospital from March 2016 to April 2019 (research group, RG) and 30 patients with benign ovarian tumor at the same time (control group, CG) were collected as research objects in this experiment. qRT-PCR and ELISA were used to detect and observe the expression levels of miR-152 in patient tissues and CYFRA21-1 in serum. ROC curves were drawn to analyze the diagnostic value of miR-152 and CYFRA21-1 in OC. The clinicopathological correlation analysis was observed, Pearson was used to examine the correlation between the expression levels of miR- 152 and CYFRA21-1 and carcinoembryonic antigen (CEA), and the 3-year survival rate of patients was observed according to the high and low expression of miR-152 and CYFRA21-1. qRT-PCR and ELISA showed that the miR-152 expression in the RG was dramatically lower than that in the CG, while CYFRA21-1 (μg/L) was remarkably higher than that in the CG (<i>p</i> < 0.05). ROC was drawn based on the miR- 152 and CYFRA21-1 expression levels. The area under miR-152 curve was 0.724 (<i>p</i> < 0.05), and the area under CYFRA21-1 curve was 0.714 (<i>p</i> < 0.05). The expression levels of miR-152 and CYFRA21-1 were relevant to lymph metastasis, differentiation degree and pathological stage of OC patients (<i>p</i> < 0.05). Pearson test analysis identified that miR-152 and CYFRA21-1 were positively correlated with CEA (<i>p</i> < 0.001). The 3-year overall survival rate of miR-152 Low Expression Group (LEG) was 61.54%, that of high expression group (HEG) was 84.85%, that of CYFRA21-1 LEG was 83.75%, and that of HEG was 60.54%. miR-152 shows low expression in the tissues of patients and CYFRA21-1 shows high expression in serum, and both indexes have good diagnostic efficacy. The higher the miR-152 expression is, the higher the survival rate is, while the higher the CYFRA21-1 expression is, the lower the survival rate is.

Evaluation of the value of preoperative CYFRA21-1 in the diagnosis and prognosis of epithelial ovarian cancer in conjunction with CA125

Growing evidence indicates that the tumor biomarker cytokeratin 19 fragment (CYFRA21-1) is significant for a variety of cancers. However, its role in epithelial ovarian cancer (EOC) has rarely been reported. In this study, a receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CYFRA21-1. The correlation between the CYFRA21-1 level and prognosis was analyzed by Kaplan-Meier survival analysis and univariable and multivariable analyses. The relationship between serum CYFRA21-1 levels and different clinicopathological variables was also analyzed. At the same time, the standard serum marker cancer antigen 125 (CA125) was measured. The results demonstrated that CYFRA21-1 expression was significantly increased in EOC compared with expression in benign ovarian diseases and healthy controls, which was similar to CA125 (P < 0.001). CYFRA21-1 expression was positively correlated with CA125 (r = 0.201; P = 0.0032). CYFRA21-1 expression was significantly correlated with lymph node metastasis and ascites (P < 0.001). Furthermore, the median survival time of EOC patients with high CYFRA21-1 expression was 42 months, compared with 54 months in the low CYFRA21-1 expression patients by Kaplan-Meier analysis (P < 0.05), while the high and low CA125 expression groups had no difference in median survival time. Univariate and multivariate analyses indicated that CYFRA21-1 was a poor prognostic factor associated with overall survival (OS), while CA125 was not. Our study indicates that CYFRA21-1 acts as a good complementary diagnostic biomarker and may be superior to CA125 as a prognostic indicator in EOC.

Valuable Serum Markers in Pulmonary Alveolar Proteinosis.

Objective Several serum markers were reported to reflect the severity of pulmonary alveolar proteinosis (PAP). The aim of this study is to investigate a reliable and facile marker to access and monitor the clinical course of PAP in a large cohort. Methods PAP patients from January 2010 to June 2018 were enrolled. Hospital records were used as data sources. The levels of various serum indicators were detected. We evaluated the correlation between pulmonary function test results and clinical variables. Results Diffusion capacity for carbon monoxide (DLCO) level was positively correlated with the level of high-density lipoprotein cholesterol (HDL-C) (P < 0.05) in 122 patients of PAP at baseline. The levels of HDL-C and DLCO significantly increased while carcinoembryonic antigen (CEA), CYFRA21-1, neuron-specific enolase (NSE), and lactic dehydrogenase (LDH) levels decreased six months after granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation therapy between 14 patients with PAP. Nevertheless, the increased DLCO was significantly correlated with decreased CEA (r = ‐0.579, P = 0.031) and CYFRA 21-1 (r = ‐0.632, P = 0.015). In 10 PAP patients without GM-CSF inhalation therapy, HDL-C and DLCO significantly decreased while NSE and LDH levels increased after six months of follow-up. The decreased DLCO was significantly correlated with increased LDH (r = ‐0.694, P = 0.026). Conclusions Serum CEA, CYFRA21-1, and LDH are valuable serum markers for the evaluation of disease activity of PAP and may predict the response to treatment of PAP.

The Application Value of Serum HE4 in the Diagnosis of Lung Cancer.

Background:To investigate the clinical value of HE4 detection in the diagnosis of lung cancer and the clinical significance of combined detection with CEA, NSE and CYFRA21-1. Methods:90 cases of lung cancer, 30 cases of pulmonary tuberculosis, 30 cases of pneumonia and 30 cases of health physical examination were selected. The levels of serum HE4, CYFRA21-1, CEA and NSE were detected by electrochemiluminescence method. Statistical analysis was performed to observe the sensitivity and specificity. Results:The levels of serum HE4, CEA, NSE and CYFRA21-1 in lung cancer group were significantly higher than those in tuberculosis group and health physical examination group. There was no significant difference in the levels of HE4, CEA and NSE between the lung cancer group and the pneumonia group, the difference of CYFRA21-1 level was statistically significant (p<0.05).With health physical examination group as normal controls, the sensitivity and specificity of combined detection of HE4, CEA, NSE and CYFRA21-1 in the diagnosis of lung cancer were 82.2% and 90.0%,and the area under the curve (AUC) was 0.907, followed by HE4 (0.867), CYFRA21-1 (0.787), CEA (0.752) and NSE (0.747). Conclusion: HE4 can be used as a serological marker for the diagnosis of lung cancer. The combined detection of HE4, CEA, NSE and CYFRA21-1 can improve the diagnosis of lung cancer. Serum HE4 levels are highly specific in distinguishing between lung cancer patients and normal population, and are equivalent to CYFRA21-1; but they are less specific than CYFRA21-1 in distinguishing lung cancer patients from pneumonia patients.

Serum thrombospondin-2 is a candidate diagnosis biomarker for early non-small-cell lung cancer

Thrombospondin-2 (THBS2) is a secreted protein overexpressed in numerous cancers and may function as a diagnostic tumor marker. The objective of the present study was to investigate the diagnostic performance of serum THBS2 in early stage non-small-cell lung cancer (NSCLC). Serum THBS2 and Cyfra21-1 level were evaluated in blood samples of 112 patients from NSCLC groups and 51 healthy control (HC) groups. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic significance. Serum THBS2 level was significantly up-regulated in NSCLC patients compared with healthy control subjects (P<0.0001), and the postoperative THBS2 level decreased significantly (P<0.0001). ROC curves analysis demonstrated that THBS2 was a comparable biomarker as Cyfra21-1 to distinguish early stage NSCLC or lung squamous cell carcinoma (SC) from healthy control subjects. And Cyfra21-1 was observed with significantly improved performances by the combination of THBS2 to distinguish early stage NSCLC (P<0.05) as well as SC (P<0.05) from the control subjects. In addition, THBS2 was estimated to perform well in the diagnosis of patients with Cyfra21-1-negative NSCLC (area under the curve [AUC] = 0.73). In summary, the present study suggested that serum THBS2 might be an early diagnostic biomarker for NSCLC.

Serum CYFRA 21-1 but not Vimentin is Associated with Poor Prognosis in Advanced Lung Cancer Patients.

Background:Cytokeratins and Vimentin are intermediate filament proteins. Vimentin expression in tissue samples has been reported to be associated with a poor prognosis in non-small cell lung cancer patients who underwent surgery. CYFRA 21-1 (Cytokeratin 19 Fragment) is a well known tumor marker.Objective:This study aimed to investigate the usefulness of serum vimentin as a tumor marker and significance of CYFRA 21-1 and vimentin expression on prognosis of advanced lung cancer patients.Methods:One hundred and four advanced lung cancer patients and 19 non-lung cancer patients were included. A total of 157 clinical samples obtained from 113 patients was used for immunostaining of vimentin and measurements of CYFRA 21-1 and vimentin concentrations.Results:Compared to low concentration, high concentration of serum CYFRA 21-1 was associated with shorter overall survival in lung cancer patients. However, there was no difference in the serum vimentin concentration between the patients with lung cancer and those with non-lung cancer. No difference in vimentin concentration was observed between the malignant and non-malignant pleural effusions. Immunostaining revealed that of the 43 tumor samples, 21 were positive and 22 were negative for vimentin. No significant difference was found in overall survival between patients with positive and negative for vimentin.Conclusion:An elevated serum CYFRA 21-1 concentration was associated with shorter overall survival in advanced lung cancer patients. However, serum vimentin was not as useful as a tumor marker of lung cancer. The vimentin positivity in tumor samples might not predict patients’ prognosis in patients with advanced lung cancer.

Serum cytokeratin 19 fragment 21-1 and carcinoembryonic antigen combination assay as a biomarker of tumour progression and treatment response in extramammary Paget disease.

Extramammary Paget disease (EMPD) is a rare intraepithelial adenocarcinoma affecting the genitals and axillary regions. As metastasis of these tumours is itself rare, solid disease management strategies have not been established. Serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 21-1 (CYFRA 21-1) levels have been identified as candidate biomarkers for tumour progression in EMPD. To determine the accuracy of and the correlation between these markers in patients with EMPD. Serum CEA and CYFRA 21-1 levels were examined in 30 patients with EMPD treated at Keio University Hospital, and compared against clinical information. Both assays were performed at the time of diagnosis, during the postoperative observation period, and following systemic treatment in those with confirmed metastasis. Serum levels were then correlated with tumour progression status and treatment responses. Normal levels for both assays were observed in all 11 patients with primary localized disease (100%). In patients with metastatic disease the CEA positivity rate was 79% (15 of 19 patients), with a rate of 63% (12 of 19 patients) for CYFRA 21-1. Changes in CEA and CYFRA 21-1 levels were statistically independent; however, using a combined view, elevated levels of either marker improved the positivity rate to 95% (18 of 19 patients). Use of both markers also correlated well with treatment responses. The combination of CEA and CYFRA 21-1 is useful for predicting metastasis and treatment response in patients with EMPD, especially in those who only have elevation of a single marker. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokine 19 fragment 21-1 (CYFRA 21-1) have been shown to be elevated in patients with extramammary Paget disease (EMPD). Elevation of serum CEA levels is associated with tumour progression of EMPD. A single small study reported that serum CYFRA 21-1 levels are elevated in patients with EMPD with lymph node metastasis. What does this study add? Serum CEA and CYFRA 21-1 were present in 79% and 63% of 19 cases of metastatic EMPD, respectively. Elevations of CEA and CYFRA 21-1 were statistically independent. CEA and CYFRA 21-1 combination assays were positive in 95% of cases of metastatic EMPD. What is the translational message? Combination assays with CEA and CYFRA 21-1 are useful for monitoring treatment response in patients with metastatic EMPD, particularly in those with elevation of either marker.

Carcinoembryonic antigen and CYFRA 21-1 responses as prognostic factors in advanced non-small cell lung cancer

It is unclear whether changes in serum tumor marker expression post-treatment are of prognostic value. We investigated the associations between changes in serum carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA 21-1) after first-line treatment and overall survival (OS) in non-small cell lung cancer (NSCLC). Advanced NSCLC patients (April 2010 to December 2015) with elevated serum CEA or CYFRA 21-1 were included. The associations between tumor marker changes after treatment initiation and OS were analyzed. Ninety-six and 55 patients were CEA- and CYFRA 21-1-positive, respectively. The serum CEA response at 4 months and CYFRA 21-1 responses at 1 and 4 months were significantly associated with OS in the univariate analyses (P=0.025, P=0.016 and P<0.001, respectively). Moreover, in the multivariate analyses, serum CYFRA 21-1 response at 4 months was significantly associated with improved OS (P=0.038). In NSCLC patients, serum CEA and CYFRA 21-1 responses after treatment initiation may predict longer OS.

Clinical characteristics and prognosis of nonsurgically treated patients with pneumonic-type adenocarcinoma.

Pneumonic-type adenocarcinoma (P-ADC) is a subtype of lung adenocarcinoma with high mortality, which often requires lobectomy surgery. Nonsurgically treated P-ADC patients usually have more advanced or complex conditions, which remain poorly understood and pose a major challenge in clinical management. We aimed to describe the clinical profiles and prognosis of non-surgically treated P-ADC patients. We enrolled 71 patients with pathologically proven P-ADC from a university hospital in China. Clinical and laboratory data were retrieved from medical record. Their median age was 62 years, including 45% men and 35% smokers. Clinical manifestations were dominated by cough, sputum, and dyspnea. Main chest imaging features included nodules, shadow, consolidation, and air bronchogram. Nearly half or more of patients showed higher levels of inflammation and cancer biomarkers including cytokeratin-19-fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA). Majority of patients were classified at the stage IIIB or IV. Palliative care was the most popular treatment option but provided a shorter overall survival compared to tyrosine kinase inhibitor therapy, standard chemotherapy, and sequential therapy while there were no significant differences in the survival among the latter 3 options. Higher serum CEA was associated with longer survival and better prognosis while higher serum CYFRA 21-1 could predict a poor prognosis. Detailed understanding the clinical characteristics and prognostic factors in nonsurgically treated P-ADC may allow the identification of patients with particular risk factors and initiation of early and specific treatment in order to optimize outcomes.

Compensated Interferometry Measures of CYFRA 21-1 Improve Diagnosis of Lung Cancer.

Diagnosis of lung cancer patients with indeterminate pulmonary nodules (IPNs) presents a significant clinical challenge, with morbidity and management costs of $28 billion/year. We show that a quantitative free-solution assay (FSA), coupled with a compensated interferometric reader (CIR), improves the diagnostic performance of CYFRA 21-1 as a lung cancer biomarker. FSA-CIR is a rapid, mix-and-read, isothermal, label- and enzyme-free, matrix-insensitive, and target and probe-agnostic assay. Operating FSA-CIR at ∼40, 0.75 μL samples/day delivered a serum CYFRA 21-1 limit of quantification (LOQ) of 81 pg/mL with intra-assay and interassay CVs of 4.9% and 9.6% for four-day replicate determinations. Blinded analysis of a 225 patient cohort, consisting of 75 nonmalignant nodules, 45 adenocarcinomas, 44 squamous cell carcinomas, and 61 small cell lung cancers, gave a clear separation of cases and controls, not observed in the Cobas ECL analysis. The area under the curve (AUC) for the Mayo model increased from 0.595 to 0.923 when combined with the FSA-CIR CYFRA 21-1 measurements. In a population with nodules between 6 and 30 mm, the AUC increased from 0.567 to 0.943. In this subgroup, the positive predictive value (PPV) for all tumors by the CYFRA 21-1 assay was 98.7%. Our results demonstrate increased performance of the CYFRA 21-1 assay using FSA-CIR and represents a proof of concept for redefining the performance characteristics of this important candidate biomarker.

Potential for the blood-based biomarkers cytokeratin 19 fragment (CYFRA 21-1) and human epididymal protein 4 (HE4) to detect recurrence during monitoring after surgical resection of adenocarcinoma of the lung

ObjectivesThe biomarkers cytokeratin 19 fragment (CYFRA 21-1) and human epididymis protein 4 (HE4) are useful in the diagnosis, prognosis, and monitoring of non-small cell lung cancer (NSCLC), but their combination has not been investigated yet. The objective of this analysis was to evaluate the ability of CYFRA 21-1 and HE4 to predict recurrence as part of follow-up monitoring in patients with adenocarcinoma (ADC) of the lung. Materials and methodsSerum samples were collected from patients with stage I-IIIA ADC preoperatively and during follow-up at 3, 6, 12, 18, and 24 months and then every 6–12 months up to 5 years post-R0 resection. Samples were analyzed for CYFRA 21-1 and HE4 via electrochemiluminescence immunoassay. All cases of disease recurrence were verified by imaging. The diagnostic performance of CYFRA 21-1, HE4, and their combination to predict recurrence was assessed by Receiver Operating Characteristic (ROC) and corresponding area under the curve (AUC). Results115 patients with ADC were included (N = 612 biomarker measurements); median age was 63 years; most had stage I–II disease (n = 97; 84.3%). All patients underwent surgical resection; 44 patients (38%) also received adjuvant chemotherapy and 16 (14%) received radiation therapy. At the median timepoint for the last blood sample collection (37 months), 31 patients (27%) had experienced recurrence. Both CYFRA 21-1 and HE4 were able to detect recurrence (AUC and 95% confidence interval [CI]): 75.9% (66.0–85.8%) and 75.4% (65.9–84.8%), respectively, but this increased with the combination (78.8% [69.0–88.6%]). At a sensitivity of 80%, the respective specificities (95% CI) for CYFRA 21-1, HE4, and the combination were 57.1% (53.0–61.2%), 57.1% (53.0–61.2%), and 69.7% (65.8–73.4%). ConclusionSerial measurements of serum CYFRA 21-1 and HE4 levels could provide a valuable method for follow-up monitoring of patients with ADC to detect recurrence.

CYFRA 21-1 and Placental Growth Factor as Screening Markers for Endometriosis.

BackgroundThis study evaluated the performance of serum CYFRA 21-1 and placental growth factor (PIGF) as screening markers for endometriosis.Material/MethodsIn this prospective study included 81 female patients who underwent laparoscopy to treat benign ovarian tumors. Serum samples were obtained from all study patients before surgery. Serum marker levels, including CYFRA 21-1, PIGF, cancer antigen (CA)125, CA19-9, and human epididymis protein 4 (HE4) were measured using a fluorescence immunoassay technique.ResultsForty of the patients were diagnosed with endometriosis (the study group) and 41 women were diagnosed with other benign ovarian tumors (the control group). Mean serum CYFRA 21-1 and PIGF levels were not different between these 2 groups (P=0.179 and P=0.865, respectively). Elevated serum CA125 levels (>35 U/mL) and lower CYFRA 21-1 levels (≤2.29 ng/mL) were more frequently observed in the endometriosis study group than in the control group (P<0.0001, and P=048, respectively). High serum PIGF levels (>14.2 pg/mL) were observed in both groups (P=0.226). Mean serum CA19-9 levels and HE4 levels, as well as the ROMA (risk of ovarian malignancy Algorithm) score were similar between the 2 groups. Sensitivity (95.0%) and negative predictive value (NPV) (80.0%) of CYFRA 21-1 for diagnosing endometriosis were higher than those of CA125 (sensitivity 67.5%, NPV 74.5%) and PIGF (sensitivity 20.0%, NPV 53.6%). However, the specificity (PIGF 90.2%, CA125 92.7%) and positive predictive value (PPV) (PIGF 66.7%, CA125 87.1%) of PIGF and CA125 for diagnosing endometriosis were higher than those of CYFRA 21-1 (specificity 19.5%, PPV 53.5%).ConclusionsCYFRA 21-1 and PIGF may be promising markers to identify patients with and without ovarian endometriosis.

Establishment and Verification of A Novel Predictive Model of Malignancy for Non-solid Pulmonary Nodules

背景与目的数学预测模型是判断肺小结节恶性概率的有效工具。伴随肺癌流行病学趋势的改变，以非实性肺小结节为影像学表现的早期肺癌检出率逐年升高，准确鉴别并及时治疗干预可有效改善预后。本研究旨在专门针对非实性肺小结节构建新型恶性概率预测模型，为有创诊疗提供客观依据，并尽量避免不必要的侵袭性操作及其可能造成的严重后果。方法回顾性分析自2013年1月-2018年4月，单中心经穿刺活检或手术切除获得明确病理诊断的362例非实性肺小结节病例资料，包括临床基本资料、血清肿瘤标记物和影像学特征等。病例分两组，应用建模组数据做单因素分析和二分类Logistic回归，判定独立危险因素，建立预测模型；应用验证组数据验证模型预测价值并与其他模型比较。结果362例非实性肺小结节病例中，313例（86.5%）确诊为非典型腺瘤样增生（atypical adenomatous hyperplasia, AAH）/原位腺癌（adenocarcinoma in situ, AIS）、微浸润腺癌（minimally invasive adenocarcinoma, MIA）或浸润性腺癌，49例诊断为良性病变。年龄、血清肿瘤标记物癌胚抗原（carcino-embryonic antigen, CEA）和Cyfra21-1、肿瘤实性成分比值（consolidation tumor ratio, CTR）、分叶征和钙化被确定为独立危险因素。模型受试者工作曲线下面积为0.894。预测灵敏度为87.6%，特异度为69.7%，阳性预测94.8%，阴性预测值为46.9%。经验证模型预测价值显著优于VA、Brock和GMUFH模型。结论本研究建立的新型非实性肺小结节恶性概率预测模型具备较高的诊断灵敏度和阳性预测值。经初步验证，其预测价值优于传统模型。未来经大样本验证后，可用作高危非实性肺小结节活检或手术切除前的初筛方法，具备临床应用价值。