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A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer.

ABSTRACT: Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, and showed a good diagnostic performance across a range of lung tumor types, emphasizing its high specificity and positive predictive value. We next tested its utility in two clinically relevant contexts: assessment of lung cancer risk and nodule malignancy. The scores derived from the model were associated with a significantly higher risk of having lung cancer in asymptomatic individuals enrolled in a computed tomography (CT)-screening program (OR = 1.89; 95% CI = 1.20-2.97). Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80-0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up.

SUBMITTER: Ajona D

PROVIDER: S-EPMC8931205 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer.

Ajona Daniel D Remirez Ana A Sainz Cristina C Bertolo Cristina C Gonzalez Alvaro A Varo Nerea N Lozano María D MD Zulueta Javier J JJ Mesa-Guzman Miguel M C Martin Ana A Perez-Palacios Rosa R Perez-Gracia Jose Luis JL Massion Pierre P PP Montuenga Luis M LM Pio Ruben R

Translational research : the journal of laboratory and clinical medicine 20210219

Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, a ...[more]

PMID: 33618009

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Project description:Serum cytokeratin 19 fragment (CYFRA21-1) has been found to be a useful prognostic marker in lung cancer. Previous studies have revealed that change in CYFRA21-1 synchronously predicted therapeutic effectiveness in advanced nonsmall cell lung cancer (NSCLC) after the second cycle of chemotherapy. The objective of this study was to investigate the early predictive value of percentage change in serum CYFRA21-1 from pretreatment to completion of the first cycle of chemotherapy for chemotherapeutic effectiveness in advanced NSCLC patients.Ninety-seven advanced NSCLC patients with elevated serum CYFRA21-1 level (?3.8??g/L), who received 2 platinum-containing drugs, were included in this retrospective study. Serum CYFRA21-1 had been assayed before and after the first cycle of chemotherapy. To evaluate the effectiveness of chemotherapy, patients were allocated to disease control (DC) and progressive disease groups. The percentage changes of serum CYFRA21-1 concentration before and after first-cycle chemotherapy that occurred in each group were evaluated for their ability to predict achievement of radiologic DC, that is, to predict therapeutic effectiveness.The percentage change of serum CYFRA21-1 and the prevalence of ?5% weight loss were higher in patients with progressive disease than in those with DC. The differences in other clinical and pathological variables including age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, cigarette smoking, histological type, gross type, clinical stage, and chemotherapy regimens of the 2 groups were not significant. Both multiple generalized linear model analysis and linear trend tests indicated that the percentage change of serum CYFRA21-1 concentration was independently and negatively linked to the effectiveness of chemotherapy for NSCLC (P?<?0.01). The area under the receiver-operating characteristic curve of the percentage change in prediction of DC was 0.84 and the optimal cut-off value was17.5% (P?<?0.001).The percentage change of serum CYFRA21-1 after completing the first cycle of chemotherapy was predictive of treatment effects and might be helpful in making early decisions to change chemotherapy regimens in patients with advanced NSCLC.

Project description:PURPOSE: Among diverse tumor markers, pretreatment evaluation and follow-up detection of recurrence in colorectal cancer are generally evaluated by serum carcinoembryonic antigen (CEA) levels. However, there have been some reports about the low accuracy and high false-positive results of CEA in colorectal cancer. We investigated the clinical utilities of CYFRA 21-1 by comparing CEA and cancer antigen 19-9 (CA 19-9) in pretreatment and recurrent colorectal cancer. METHODS: Using a solid-phase immunoradiometric assay, serum levels of CYFRA 21-1, CEA and CA 19-9 were analyzed in 132 patients with primary colorectal cancer, 124 healthy controls, 104 patients with benign colorectal disease and 19 patients with recurrent colorectal cancer. We determined three different cutoff values to evaluate the sensitivity of diagnostic performance in pretreatment and recurrent colorectal cancer. RESULTS: CYFRA 21-1 (? 1.13 ng/ml) had a sensitivity of 47 %, compared with 37 % for CEA (? 3.05 ng/ml) and 32.6 % for CA 19-9 (? 23.1 ng/ml) in the initial staging of primary colorectal cancer. Using different cutoff values, CYFRA 21-1 showed higher sensitivity for pretreatment colorectal cancer than CEA and CA 19-9 in adenocarcinoma and adenosquamous carcinoma of this study. A mildly significant correlative relationship was noted between Dukes' stages and three tumor markers (p?<?0.01). The areas under the receiver operating characteristic curves of CYFRA 21-1, CEA and CA 19-9 were 0.81?±?0.03, 0.74?±?0.03 and 0.62?±?0.04, respectively, for discriminating colorectal cancer patients from patients with benign colorectal disease. In addition, CYFRA 21-1 was determined as the most sensitive tumor marker for evaluating recurrent colorectal cancer for all cutoff values. CONCLUSION: This study showed that CYFRA 21-1 could be a useful and dependable tumor marker for pretreatment and recurrent colorectal cancer. Further prospective studies on its usefulness with respect to the prognosis and utility of combined tumor markers are needed.

Dataset Information

A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer.

Publications

A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer.

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