Quantification of CYFRA 21-1 and a CYFRA 21-1–anti-CYFRA 21-1 autoantibody immune complex for detection of early stage lung cancer

Song, Ki-Bong; Nimse, Satish Balasaheb; Warkad, Shrikant Dashrath; Oh, Ae-Chin; Kim, Taisun; Hong, Young Jun

doi:10.1039/c9cc03620b

Cited by 13 publications

(16 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the use of the PIC/Tp53 ratio allows the detection of lung cancer with 78.7% sensitivity and a specificity of 93.3%. We recently reported a detection method for the CYFRA 21-1 antigen and CYFRA 21-1-Anti-CYFRA 21-1 autoantibody immune complex (CIC) [ 40 ]. The levels of these markers can be used to determine the CIC/CYFRA21-1 ratio, as shown in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

Detection and Quantification of Tp53 and p53-Anti-p53 Autoantibody Immune Complex: Promising Biomarkers in Early Stage Lung Cancer Diagnosis

Song¹,

Nimse

Warkad³

et al. 2022

Biosensors

Self Cite

View full text Add to dashboard Cite

Lung cancer is a leading cause of death worldwide, claiming nearly 1.80 million lives in 2020. Screening with low-dose computed tomography (LDCT) reduces lung cancer mortality by about 20% compared to standard chest x-rays among current or heavy smokers. However, several reports indicate that LDCT has a high false-positive rate. In this regard, methods based on biomarker detection offer excellent potential for developing noninvasive cancer diagnostic tests to complement LDCT for detecting stage 0∼IV lung cancers. Herein, we have developed a method for detecting and quantifying a p53-anti-p53 autoantibody complex and the total p53 antigen (wild and mutant). The LOD for detecting Tp53 and PIC were 7.41 pg/mL and 5.74 pg/mL, respectively. The detection ranges for both biomarkers were 0–7500 pg/mL. The known interfering agents in immunoassays such as biotin, bilirubin, intra-lipid, and hemoglobin did not detect Tp53 and PIC, even at levels that were several folds higher levels than their normal levels. Furthermore, the present study provides a unique report on this preliminary investigation using the PIC/Tp53 ratio to detect stage I–IV lung cancers. The presented method detects lung cancers with 81.6% sensitivity and 93.3% specificity. These results indicate that the presented method has high applicability for the identification of lung cancer patients from the healthy population.

show abstract

Section: Resultsmentioning

confidence: 99%

Detection and Quantification of Tp53 and p53-Anti-p53 Autoantibody Immune Complex: Promising Biomarkers in Early Stage Lung Cancer Diagnosis

Song¹,

Nimse

Warkad³

et al. 2022

Biosensors

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interestingly, in our previous study, we found that the plasma levels of CYFRA 21-1-Anti-CYFRA 21-1 autoantibody immune complex (CIC) were at higher levels in lung cancer patients than in the healthy population. However, CIC's plasma levels were at lower levels compared to the free CYFRA 21-1 in a healthy population than in lung cancer patients [37]. Therefore, it was assumed that using these two biomarkers in lung cancer detection could allow high sensitivity and specificity.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently reported on the quantification of CYFRA 21-1 and CYFRA 21-1-Anti-CYFRA 21-1 autoantibody immune complex (CIC) to detect early-stage lung cancer [37]. Based on our findings, we have developed a 9G test TM Cancer/Lung, a test that allows the diagnosis of stage 0~IV lung cancers.…”

Section: Introductionmentioning

confidence: 99%

9G TestTM Cancer/Lung: A Desirable Companion to LDCT for Lung Cancer Screening

Choe

Chae

Lee

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

A complimentary biomarker test that can be used in combination with LDCT for lung cancer screening is highly desirable to improve the diagnostic capacity of LDCT and reduce the false-positive rates. Most importantly, the stage I lung cancer detection rate can be dramatically increased by the simultaneous use of a biomarker test with LDCT. The present study was conducted to evaluate 9G testTM Cancer/Lung’s sensitivity and specificity in detecting Stage 0~IV lung cancer. The obtained results indicate that the 9G testTM Cancer/Lung can detect lung cancer with overall sensitivity and specificity of 75.0% (69.1~80.3) and 97.3% (95.0~98.8), respectively. The detection of stage I, stage II, stage III, and stage IV cancers with sensitivities of 77.5%, 78.1%, 67.4%, and 33.3%, respectively, at the specificity of 97.3% have never been reported before. The receiver operating characteristic curve analysis allowed us to determine the population-weighted AUC of 0.93 (95% CI, 0.91–0.95). These results indicate that the 9G testTM Cancer/Lung can be used in conjunction with LDCT to screen lung cancer. Furthermore, obtained results indicate that the use of 9G testTM Cancer/Lung with LDCT for lung cancer screening can increase stage I cancer detection, which is crucial to improve the currently low 5-year survival rates.

show abstract

“…Blood tumor biomarkers are potential for early diagnosis of LC as they have advantages of non-invasion and convenient to access (10,11). However, multiple tumor biomarkers utilized in clinical practice show low diagnostic accuracy for cancer, such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin-19 fragment (CYFRA 21-1) (12)(13)(14). Tumor-associated antigens (TAAs) refer to antigen molecules that exist on tumor cells or normal cells, but they are abnormally expressed in diverse cancers (15).…”

Section: Introductionmentioning

confidence: 99%

Discovering Panel of Autoantibodies for Early Detection of Lung Cancer Based on Focused Protein Array

et al. 2021

View full text Add to dashboard Cite

Substantial studies indicate that autoantibodies to tumor-associated antigens (TAAbs) arise in early stage of lung cancer (LC). However, since single TAAbs as non-invasive biomarkers reveal low diagnostic performances, a panel approach is needed to provide more clues for early detection of LC. In the present research, potential TAAbs were screened in 150 serum samples by focused protein array based on 154 proteins encoded by cancer driver genes. Indirect enzyme-linked immunosorbent assay (ELISA) was used to verify and validate TAAbs in two independent datasets with 1,054 participants (310 in verification cohort, 744 in validation cohort). In both verification and validation cohorts, eight TAAbs were higher in serum of LC patients compared with normal controls. Moreover, diagnostic models were built and evaluated in the training set and the test set of validation cohort by six data mining methods. In contrast to the other five models, the decision tree (DT) model containing seven TAAbs (TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1), built in the training set, yielded the highest diagnostic value with the area under the receiver operating characteristic curve (AUC) of 0.897, the sensitivity of 94.4% and the specificity of 84.9%. The model was further assessed in the test set and exhibited an AUC of 0.838 with the sensitivity of 89.4% and the specificity of 78.2%. Interestingly, the accuracies of this model in both early and advanced stage were close to 90%, much more effective than that of single TAAbs. Protein array based on cancer driver genes is effective in screening and discovering potential TAAbs of LC. The TAAbs panel with TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1 is excellent in early detection of LC, and they might be new target in LC immunotherapy.

show abstract

Quantification of CYFRA 21-1 and a CYFRA 21-1–anti-CYFRA 21-1 autoantibody immune complex for detection of early stage lung cancer

Abstract: Population-based screening of stage 0–I lung cancer is crucial for saving lives. The CIC/CYFRA 21-1 ratio allows the detection of stage I lung cancer with 76.0% sensitivity and 87.5% specificity.

Cited by 13 publications

References 27 publications

Detection and Quantification of Tp53 and p53-Anti-p53 Autoantibody Immune Complex: Promising Biomarkers in Early Stage Lung Cancer Diagnosis

Detection and Quantification of Tp53 and p53-Anti-p53 Autoantibody Immune Complex: Promising Biomarkers in Early Stage Lung Cancer Diagnosis

9G TestTM Cancer/Lung: A Desirable Companion to LDCT for Lung Cancer Screening

Discovering Panel of Autoantibodies for Early Detection of Lung Cancer Based on Focused Protein Array

Contact Info

Product

Resources

About