Novel panel of protein biomarkers to predict response to bortezomib-containing induction regimens in multiple myeloma patients

新型蛋白质生物标志物组合可预测多发性骨髓瘤患者对含硼替佐米诱导方案的反应

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作者:Kay Reen Ting, Michael Henry, Justine Meiller, Annemarie Larkin, Martin Clynes, Paula Meleady, Despina Bazou, Paul Dowling, Peter O'Gorman

Background

Multiple myeloma (MM) is a complex heterogeneous disease. Various risk stratification models have been recommended including cytogenetic and FISH analysis to identify high-risk patients who may benefit from novel treatments, but such facilities are not widely available. The International Scoring System (ISS) using beta-2-microglobulin and albumin remains a widely used prognostic scoring system in many clinical practices; however it is not useful in predicting response to treatment in MM. The

Conclusions

A combination of new and standard biomarkers consisting of CLU, ANG, C1Q, albumin, ß2M, paraprotein and K/L ratio may have potential as a novel panel of biomarkers to predict MM response to treatment containing bortezomib. General significance: Use of this biomarker panel could facilitate a more personalized therapy approach and to minimize unnecessary side effects from ineffective drugs.

Methods

17 MM patient serum samples (9 responders/8 non-responders) were used for the discovery phase (label-free mass spectrometry) and an additional 20 MM patient serum samples were used for the ELISA-based validation phase (14 responders/6 non-responders).

Results

CLU and ANG mean levels were higher in the responders group, while Complement C1q had lower concentrations. The combination of all standard biomarkers (albumin, beta-2-microglobulin (ß2M), paraprotein and kappa/lambda (K/L) ratio) had an AUC value of 0.71 with 65% correct classification, while an overall combination of new candidate protein biomarkers with standard biomarkers had an AUC value of 0.89 with 85.3% correct classification. Conclusions: A combination of new and standard biomarkers consisting of CLU, ANG, C1Q, albumin, ß2M, paraprotein and K/L ratio may have potential as a novel panel of biomarkers to predict MM response to treatment containing bortezomib. General significance: Use of this biomarker panel could facilitate a more personalized therapy approach and to minimize unnecessary side effects from ineffective drugs.

Significance

Use of this biomarker panel could facilitate a more personalized therapy approach and to minimize unnecessary side effects from ineffective drugs.

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