Receiver operating characteristic analysis

Klingenstein, Annemarie; Haritoglou, Ingrid; Schaumberger, Markus; Nentwich, Martin M.; Hein, Rüdiger; Schaller, U. C.

doi:10.1097/cmr.0b013e328347105e

Cited by 16 publications

(19 citation statements)

References 23 publications

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“…Receiver operating characteristic (ROC) curves provide a graphical tool to assess the diagnostic utility of markers, and are often applied to melanoma markers, recent examples including autoantibodies [24], circulating cell-free DNA amplicons [25], and MIA [26]. A Receiver Operating Characteristic analysis for MIF showed an Area Under the Curve of 0.987 (Figure 4), and a highly significant correlation was found between MIF and MLANA (Figure 5; p<0.0001).…”

Section: Resultsmentioning

confidence: 99%

Circulating Tumor Cells in Melanoma Patients

et al. 2012

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Circulating tumor cells (CTCs) are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X) from blood of melanoma patients using a simple centrifugation device (OncoQuick), and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF) were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively) compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001). There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001), and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50%) stained for both pan-cytokeratin (KRT) markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14). Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA) may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs). The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids, and their role in metastatic progression.

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Section: Resultsmentioning

confidence: 99%

Circulating Tumor Cells in Melanoma Patients

et al. 2012

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“…MIA was described as a diagnostic serum marker of melanoma progression in 1997, when it was shown that the MIA ELISA could classify 100% of the investigated sera of stage III and stage IV patients as positive for pathological MIA concentrations (18). The correlation of a high MIA serum level with a poor clinical prognosis was also confirmed by later studies for melanoma including uveal melanoma (19)(20)(21).…”

Section: Mia As a Serum Melanoma Marker Todaymentioning

confidence: 87%

Melanoma inhibitory activity in melanoma diagnostics and therapy – a small protein is looming large

Riechers

Bosserhoff

2013

Experimental Dermatology

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Malignant melanoma is a highly aggressive cancer with a very poor prognosis after the onset of metastasis. We have previously demonstrated that the protein melanoma inhibitory activity (MIA) is involved in the metastasis of and immunosuppression in malignant melanoma. Recently, we further established MIA as a therapeutic target to inhibit metastatic spread in malignant melanoma. We could show that an inhibition of MIA by a synthetic peptide decreased both the number of metastases as well as immunosuppression in a murine model of malignant melanoma. To control recurrence after surgical resection of a primary lesion, it is paramount to have diagnostic tools available that can detect a relapse due to the strong metastatic potential of melanoma. This follow-up is maintained with periodic re-examinations. Due to high cost and the associated radiation exposure, radiology examinations are avoided if possible. The analysis of prognostic markers in patient serum is therefore attractive. In this review, we focus on the quantitative analysis of the MIA protein as a prognostic tool because it has proven to be a useful serum marker for documenting disease progression of malignant melanoma. The MIA quantification assay itself is readily performed using an ELISA kit and common laboratory equipment. Because analysing MIA serum levels in combination with other established markers such as S100B improves their prognostic value, we feel that the quantification of MIA in the serum, among other markers, should be performed as a general standard of care in patients at risk of developing metastatic melanoma.

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“…Studies show that melanoma inhibitory activity (MIA), osteopontin (OPN) and tissue polypeptide-specific antigen cytokeratin 18 (TSP) are significantly elevated in serum of metastatic UM patients when compared with nonmetastatic patients (Table 5). They more than double in measurable concentration in serum, and a threshold has even been suggested for MIA of 8,3 ng/mL giving it a sensitivity of 82% and a negative predictive value of 97% as shown by Klingenstein et al [45], which is better than conventional serum markers. The size of the tested groups (503 UM patients in Klingenstein et al [45]) also makes it ready for clinical trials, and it is likely that the same goes for OPN and maybe even for TSP.…”

Section: Proteomicsmentioning

confidence: 99%

“…They more than double in measurable concentration in serum, and a threshold has even been suggested for MIA of 8,3 ng/mL giving it a sensitivity of 82% and a negative predictive value of 97% as shown by Klingenstein et al [45], which is better than conventional serum markers. The size of the tested groups (503 UM patients in Klingenstein et al [45]) also makes it ready for clinical trials, and it is likely that the same goes for OPN and maybe even for TSP. Vascular endothelial growth factor (VEGF) has not been shown to have a large increase with metastasis as one might expect, due to the wide interpersonal variability in serum VEGF levels [46].…”

Section: Proteomicsmentioning

confidence: 99%

“…Studies performed with the potential UM biomarkers of MIA and OPN show especially promising results in terms of increased sensitivity of detecting UM metastasis compared with conventional methods [45, 49]. However, there remains a need for an in-depth understanding of the UM metastasizing process and the identification of further potential biomarkers with proteomics centered upon

characterization of primary UM at differing stages including metastatic UM

prospective studies of biomarkers in UM patients using quick and hopefully cost effective tests

implementation into effective clinical practices.

…”

Section: Future Perspectivesmentioning

confidence: 99%

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Proteomics of Uveal Melanoma: A Minireview

Abildgaard

Vorum

2013

Journal of Oncology

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Uveal melanoma (UM) continues to be associated with a high mortality rate of up to 50% due to metastatic spread primarily to the liver. Currently there are relatively effective treatments for the primary tumor, though the management of the metastatic disease remains inadequate. Conventional diagnostic tools have a low sensitivity for detecting metastasis, and early detection of metastatic spread would allow more treatment options that could ultimately increase survival of UM patients. Advanced proteomic methods have already helped to find potential biomarkers associated with UM pathogenesis and metastasis. In the present review we discuss the field of proteomics in relation to studies elucidating biomarkers of UM, where proteins such as S-100β, osteopontin (OPN), and melanoma inhibitory activity (MIA) have been shown to be associated with metastasis.

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Receiver operating characteristic analysis

Cited by 16 publications

References 23 publications

Circulating Tumor Cells in Melanoma Patients

Circulating Tumor Cells in Melanoma Patients

Melanoma inhibitory activity in melanoma diagnostics and therapy – a small protein is looming large

Proteomics of Uveal Melanoma: A Minireview

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