A novel detection method of non–small cell lung cancer using multiplexed bead-based serum biomarker profiling

Lee, Hyun Joo; Kim, Young Tae; Park, Pil Je; Shin, Yong Sam; Kang, Kyung Nam; Kim, Yongdai; Kim, Chul Woo

doi:10.1016/j.jtcvs.2011.10.046

Cited by 30 publications

(28 citation statements)

References 22 publications

(22 reference statements)

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“…Among the validated proteins, we have confirmed the previously reported over-expression of CRP and HPT acutephase proteins in lung cancer patients, 2,24 as well as CO4A complement factor, 25 indicating a chronic active inflammation state and immune response. Recent proteomic studies showed alterations of different acute-phase proteins in distinct tumor types, which enhanced their usefulness as specific cancer biomarkers.…”

Section: Discussionsupporting

confidence: 82%

A New Biomarker Panel in Bronchoalveolar Lavage for an Improved Lung Cancer Diagnosis

Uribarri¹,

Hormaeche²,

Zalacaín

et al. 2014

Journal of Thoracic Oncology

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Section: Discussionsupporting

confidence: 82%

A New Biomarker Panel in Bronchoalveolar Lavage for an Improved Lung Cancer Diagnosis

Uribarri¹,

Hormaeche²,

Zalacaín

et al. 2014

Journal of Thoracic Oncology

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“…Comparing BSI to the bead-based assay is difficult in this case, but the BSI LOQ (not the LOD at 2σ) exhibits >1.5-fold improvement and is performed as a free-solution and label-free method. 49,50 Electrochemiluminescence assays have demonstrated detection limits comparable to ours reported here, 25,49,50 yet these assays are expensive and require substantial chemical complexity in both the assay discovery and analytical validation phase.…”

Section: Results and Discussionsupporting

confidence: 63%

“…For example Lee et al recently reported the quantification of Cyfra 21-1 using Luminex at levels as low as 0.01 ng/mL. 49 They present data for healthy patients ranging from 0.01 to 0.73 ng/mL and cancer patients having 0.66 to 2.4 ng/mL, yet the manufacturer reports a minimum detection concentration at 2 times the standard deviation of 0.059 ng/mL. Here we use a more conservative measure of performance, the LOQ, which is based on 3 times the standard deviation of the assay run over 5 days.…”

Section: Results and Discussionmentioning

confidence: 99%

Toward Rapid, High-Sensitivity, Volume-Constrained Biomarker Quantification and Validation using Backscattering Interferometry

et al. 2014

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Realizing personalized medicine, which promises to enable early disease detection, efficient diagnostic staging, and therapeutic efficacy monitoring, hinges on biomarker quantification in patient samples. Yet, the lack of a sensitive technology and assay methodology to rapidly validate biomarker candidates continues to be a bottleneck for clinical translation. In our first direct and quantitative comparison of backscattering interferometry (BSI) to fluorescence sensing by ELISA, we show that BSI could aid in overcoming this limitation. The analytical validation study was performed against ELISA for two biomarkers for lung cancer detection: Cyfra 21-1 and Galectin-7. Spiked serum was used for calibration and comparison of analytical figures of merit, followed by analysis of blinded patient samples. Using the ELISA antibody as the probe chemistry in a mix-and-read assay, BSI provided significantly lower detection limits for spiked serum samples with each of the biomarkers. The limit of quantification (LOQ) for Cyrfa-21-1 was measured to be 230 pg/mL for BSI versus 4000 pg/mL for ELISA, and for Galectin-7, it was 13 pg/mL versus 500 pg/mL. The coefficient of variation for 5 day, triplicate determinations was <15% for BSI and <10% for ELISA. The two techniques correlated well, ranging from 3–29% difference for Cyfra 21-1 in a blinded patient sample analysis. The label-free and free-solution operation of BSI allowed for a significant improvement in analysis speed, with greater ease, improved LOQ values, and excellent day-to-day reproducibility. In this unoptimized format, BSI required 5.5-fold less sample quantity needed for ELISA (a 10 point calibration curve measured in triplicate required 36 μL of serum for BSI vs 200 μL for ELISA). The results indicate that the BSI platform can enable rapid, sensitive analytical validation of serum biomarkers and should significantly impact the validation bottleneck of biomarkers.

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“…Such biomarkers are available and will be studied in the future for lung cancer detection (Choi et al, 2012; Takenaka et al, 2011; Tretiakova et al, 2011; Pesta et al, 2011; Lee et al, 2012; Tong et al, 2012; Ohira et al, 2003). Physical methods to further increase PC microcavity sensitivity are being investigated including optimization of PC microcavity length, the slow light effect in coupled PC waveguides and PC microcavity resonance mode quality factors (Chakravarty et al, 2012; Lai et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors

Chakravarty¹,

Lai²,

Zou³

et al. 2013

Biosensors and Bioelectronics

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We experimentally demonstrate label-free photonic crystal (PC) microcavity biosensors in silicon-on-insulator (SOI) to detect the epithelial-mesenchymal transition (EMT) transcription factor, ZEB1, in minute volumes of sample. Multiplexed specific detection of ZEB1 in lysates from NCI-H358 lung cancer cells down to an estimated concentration of 2 cells per micro-liter is demonstrated. L13 photonic crystal microcavities, coupled to W1 photonic crystal waveguides, are employed in which resonances show high Q in the bio-ambient phosphate buffered saline (PBS). When the sensor surface is derivatized with a specific antibody, the binding of the corresponding antigen from a complex whole-cell lysate generates a change in refractive index in the vicinity of the photonic crystal microcavity, leading to a change in the resonance wavelength of the resonance modes of the photonic crystal microcavity. The shift in the resonance wavelength reveals the presence of the antigen. The sensor cavity has a surface area of ~11 μm2. Multiplexed sensors permit simultaneous detection of many binding interactions with specific immobilized antibodies from the same bio-sample at the same instant of time. Specificity was demonstrated using a sandwich assay which further amplifies the detection sensitivity at low concentrations. The device represents a proof-of-concept demonstration of label-free, high throughput, multiplexed detection of cancer cells with specificity and sensitivity on a silicon chip platform.

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A novel detection method of non–small cell lung cancer using multiplexed bead-based serum biomarker profiling

Abstract: We confirmed that a new diagnostic method using 5 serum biomarkers profiling constructed by multivariate classification algorithms could distinguish NSCLC from healthy controls with high accuracy.

Cited by 30 publications

References 22 publications

A New Biomarker Panel in Bronchoalveolar Lavage for an Improved Lung Cancer Diagnosis

A New Biomarker Panel in Bronchoalveolar Lavage for an Improved Lung Cancer Diagnosis

Toward Rapid, High-Sensitivity, Volume-Constrained Biomarker Quantification and Validation using Backscattering Interferometry

Multiplexed specific label-free detection of NCI-H358 lung cancer cell line lysates with silicon based photonic crystal microcavity biosensors

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