Nucleosomes and CYFRA 21-1 indicate tumor response after one cycle of chemotherapy in recurrent non-small cell lung cancer

Holdenrieder, Stefan; Pawel, Joachim von; Dankelmann, Elke; Duell, Thomas; Faderl, Bernhard; Markus, Andreas; Siakavara, Maria; Wagner, Helmut; Feldmann, Knut; Hoffmann, Harald; Raith, Hannelore; Nagel, Dorothea; Stieber, P.

doi:10.1016/j.lungcan.2008.05.001

Cited by 63 publications

(45 citation statements)

References 48 publications

(93 reference statements)

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“…However, for most markers we could achieve the corresponding coefficients of variation considering the results of the quality controls provided by the manufacturer. CYFRA 21-1, a highly valuable tumor marker for non small cell lung cancer [16,23,24] , was found to be the only marker exceeding the 20% limit of CV concurring with the given imprecision by the manufacturer where it also yields the maximum coefficient of variation in the panel.…”

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confidence: 60%

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Methodical and pre-analytical characteristics of a multiplex cancer biomarker immunoassay

Hermann

Dressen

Schildberg

et al. 2014

WJM

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AIM:To test the methodical and pre-analytical performance of a new multiplex cancer biomarker panel using magnetic beads. METHODS: The MILLIPLEX® MAP Human Circulating Cancer Biomarker Magnetic Bead Panel 1 comprises the tumor markers carcinoembryonic antigen, alpha-fetoprotein, total prostate-specific antigen, cancer antigen 15-3, cancer antigen 19-9, cancer antigen 125, cytokeratine 19-fragment, β-human chorionic gonadotropin, human epididymis protein 4, osteopontin, prolactin, the cell death and angiogenesis markers soluble Fas, soluble Fas-ligand, tumor necrosis factor related apoptosisinducing ligand, vascular endothelial growth factor and the immunological markers interleukin-6 (IL-6), IL-8, tumor necrosis factor-α, transforming growth factor α, fibroblast growth factor-2, macrophage migration inhibitory factor, leptin, hepatocyte growth factor, and stem cell factor. We determined intra-and inter-assay imprecision as well as dilution linearity using quality controls and serum pools. Furthermore, the stability of the 24 biomarkers examined in this panel was ascertained by testing the influence of different storage temperatures and time span before centrifugation. RESULTS:For all markers measured in the synthetic internal quality controls, the intra-assay imprecision ranged between 2.26% and 9.41%, while for 20 of 24 measured markers in the physiological serum pools, it ranged between 1.68% and 12.87%. The inter-assay imprecision ranged between 1.48%-17.12% for 23 biomarkers in synthetic, and between 4.59%-23.88% for 18 biomarkers in physiological quality controls. Here, single markers with very low concentration levels had increased imprecision rates. Dilution linearity was acceptable (70%-130% recovery) for 20 biomarkers. Regarding pre-analytical influencing factors, most markers were stable if blood centrifugation was delayed or if serum was stored for up to 24 h at 4 ℃ and 25 ℃ after centrifugation. Comparable results were obtained in serum and plasma for most markers. However, great changes were observed for single markers. CONCLUSION: MILLIPLEX® MAP Human Circulating Cancer Biomarker Magnetic Bead Panel 1 assay is a stable and precise method for detection of most biomarkers included in the kit. However, single markers have to be interpreted with care.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Multiplex immunoassay; Tumor marker; Cytokines; Cell death markers; Methodical evaluation Core tip: In this study, the methodological quality of a new research-use-only multiplex magnetic bead assay,

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confidence: 60%

“…The same applied to 24 biomarkers in standard 5. The corresponding ranges were 2.44% (Leptin) to 27.37% (CYFRA 21-1), 1.48% (β-HCG) to 40.96% (CYFRA 21-1) and 0.32% (total PSA) to 4.15%…”

Section: Observed Concentration Based Imprecisionmentioning

confidence: 99%

Methodical and pre-analytical characteristics of a multiplex cancer biomarker immunoassay

Hermann

Dressen

Schildberg

et al. 2014

WJM

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“…However, the difference between the healthy individuals and the CRC patients did not reach statistical significance (p=0.5), while for the difference between the healthy group and MM patients there was a trend towards significance (p=0.075). The finding that CRC and MM patients have higher levels of cNUCs than healthy subjects is consistent with previous reports (3,13). ChIP assays were performed to precipitate H3K9me3 and H4K20me3-related cNUCs and qPCR to quantitate satellite 2.…”

Section: Resultssupporting

confidence: 90%

Correlation of histone methyl marks with circulating nucleosomes in blood plasma of cancer patients

et al. 2012

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Abstract.Circulating DNA is present in plasma/serum, mainly complexed with histones as nucleosomes. The detection of circulating nucleosomes (cNUCs) in the peripheral blood may be a diagnostic modality for cancer-associated changes of modified histone tails in blood circulation. In the present study, we investigated the correlation between the trimethylation of H3 lysine 9 (H3K9me3) and H4 lysine 20 (H4K20me3), which are hallmarks of pericentric heterochromatin, and cNUCs in healthy subjects and patients with colorectal cancer (CRC) and multiple myeloma (MM). The plasma concentration of cNUCs was measured using the Cell-Death Detection ELISA kit. Histone methylation marks were detected using chromatin immunoprecipitation (ChIP), followed by quantitative PCR with pericentric satellite 2 as the target sequence. The results showed a high variation in the concentrations of cNUCs, with healthy subjects exhibiting the lowest levels (median 0.194), the CRC patients intermediate (median 0.25) and the MM patients the highest levels (median 0.648). However, the differences between the groups did not reach statistical significance (p>0.05). Analysis using the Pearson's correlation test revealed a significant positive correlation between the concentration of cNUCs and H3K9me3 and H4K20me3 in the whole study group (N=57, p<0.001 for both histone marks). A study of the correlation between cNUCs and histone marks in the individual study groups demonstrated the correlation between cNUCs and H3K9me3 in CRC patients to be weak (p=0.046), indicating that circulating H3K9me3 may be modified in CRC patients. The histone marks were normalized using the values of cNUCs. In agreement with the weak correlation between cNUCs and H3K9me3 in CRC patients, H3K9me3 levels (median 0.047) were lowest in this group compared with the other two groups (0.06 in healthy subjects, 0.2 in MM patients, p = not significant). For H4K20me3, the median values were 0.022 in healthy subjects, 0.052 in CRC patients and 0.056 in MM patients. In conclusion, our findings indicate a marked correlation between cNUCs and histone methyl marks.

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“…If there were a simple method to predict the efficacy at an earlier stage, patients not responding to the treatment could be identified earlier, allowing discontinuation of the drugs or switching to other treatment options as soon as possible. Holdenrieder et al (Holdenrieder et al, 2009) reported that the detection of CYFRA 21-1 before the second chemotherapy cycle allowed the objective response to chemotherapy in advanced lung cancer to be assessed earlier than by imaging examinations. We performed subgroup analyses for patients with abnormally elevated baseline CEA or CA199 levels and calculated the serum CEA and CA199 changes after one chemotherapy cycle.…”

Section: Discussionmentioning

confidence: 99%

Changing patterns of Serum CEA and CA199 for Evaluating the Response to First-line Chemotherapy in Patients with Advanced Gastric Adenocarcinoma

Zhang¹,

Xiong²,

Lu³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Nucleosomes and CYFRA 21-1 indicate tumor response after one cycle of chemotherapy in recurrent non-small cell lung cancer

Cited by 63 publications

References 48 publications

Methodical and pre-analytical characteristics of a multiplex cancer biomarker immunoassay

Methodical and pre-analytical characteristics of a multiplex cancer biomarker immunoassay

Correlation of histone methyl marks with circulating nucleosomes in blood plasma of cancer patients

Changing patterns of Serum CEA and CA199 for Evaluating the Response to First-line Chemotherapy in Patients with Advanced Gastric Adenocarcinoma

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