A Multi-Analyte Approach for Improved Sensitivity of Liquid Biopsies in Prostate Cancer

Hofmann, Lilli; Sallinger, Katja; Haudum, Christoph; Smolle, Maria Anna; Heitzer, Ellen; Moser, Tina; Novy, Michael; Gesson, Kevin; Kroneis, Thomas; Bauernhofer, Thomas; El‐Heliebi, Amin

doi:10.3390/cancers12082247

Cited by 24 publications

(23 citation statements)

References 55 publications

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“…After applying all the selection criteria, the final sample comprised 46 articles on metastatic PC [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ] ( Supplementary Table S1 ) and 15 articles on localized PC [ 55 , 56 , 57 , 58 , 59 , 60 …”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis

Enikeev

Morozov

Babaevskaya

et al. 2022

Cancers

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The purpose of the review is to summarize the recent data on circulating tumor cells (CTC) use in clinical practice. We performed a systematic literature search using two databases (Medline and Scopus) over the past five years and the following terms: (CTC OR “circulating tumor cells” OR “liquid biopsy”) AND prostate. The primary outcome was CTC predictive value for prostate cancer (PC) progression and survival. The secondary outcomes were the CTC predictive value for therapy response and the results of CTC detection depending on the assessment method. In metastatic PC, the CTC count showed itself to be a prognostic marker in terms of clinically important features, namely survival rates and response to treatment. CTC concentration was significantly associated with the overall survival and progression-free survival rates. A strong association between the overall survival or progression-free survival rate and CTC concentration could be observed. Variant-7 androgen receptors-positive (AR-V7-positive) patients showed a poor response to androgen receptor signaling (ARS) inhibitors, but this did not compromise their response to taxanes. In localized PC, only positive Cluster of Differentiantion 82 protein (CD82+) correlated with a higher survival rate. CTC count and AR-V7 expression showed itself to be a valuable biomarker for survival in metastatic PC and response to ARS-inhibitors. CTC diagnostic performance for localized PC or for screening and early detection is not high enough to show additional value over the other biomarkers.

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Section: Resultsmentioning

confidence: 99%

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis

Enikeev

Morozov

Babaevskaya

et al. 2022

Cancers

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“…It is worth emphasizing that the ELIMA project examined not just tumor-specific variants but also variants in germline controls, e.g., 48% of cfDNA and 35% of the CTCgDNA variants were detected in the germline control (Additional file 4 : Table S3). Another recent multi-analyte liquid biopsy study using 12.5 ml blood from 19 prostate cancer patients showed an increase in the probability of obtaining tumor-related information [ 55 ]. Combinational analysis of transcripts in CTCs, the same transcripts in whole blood, and focal amplifications in cfDNA led to the identification of resistance mechanisms against prior therapy in a larger fraction of patients when compared to the evaluation using a single analyte [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…Another recent multi-analyte liquid biopsy study using 12.5 ml blood from 19 prostate cancer patients showed an increase in the probability of obtaining tumor-related information [ 55 ]. Combinational analysis of transcripts in CTCs, the same transcripts in whole blood, and focal amplifications in cfDNA led to the identification of resistance mechanisms against prior therapy in a larger fraction of patients when compared to the evaluation using a single analyte [ 55 ]. The reported sensitivity of only one analyte was around 50% and the sensitivity of the multi-analyte strategy was 89% and is similar to the results in this paper from 26 MBC patients and four LBAs.…”

Section: Discussionmentioning

confidence: 99%

Integrative statistical analyses of multiple liquid biopsy analytes in metastatic breast cancer

et al. 2021

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Background Single liquid biopsy analytes (LBAs) have been utilized for therapy selection in metastatic breast cancer (MBC). We performed integrative statistical analyses to examine the clinical relevance of using multiple LBAs: matched circulating tumor cell (CTC) mRNA, CTC genomic DNA (gDNA), extracellular vesicle (EV) mRNA, and cell-free DNA (cfDNA). Methods Blood was drawn from 26 hormone receptor-positive, HER2-negative MBC patients. CTC mRNA and EV mRNA were analyzed using a multi-marker qPCR. Plasma from CTC-depleted blood was utilized for cfDNA isolation. gDNA from CTCs was isolated from mRNA-depleted CTC lysates. CTC gDNA and cfDNA were analyzed by targeted sequencing. Hierarchical clustering was performed within each analyte, and its results were combined into a score termed Evaluation of multiple Liquid biopsy analytes In Metastatic breast cancer patients All from one blood sample (ELIMA.score), which calculates the contribution of each analyte to the overall survival prediction. Singular value decomposition (SVD), mutual information calculation, k-means clustering, and graph-theoretic analysis were conducted to elucidate the dependence between individual analytes. Results A combination of two/three/four LBAs increased the prevalence of patients with actionable signals. Aggregating the results of hierarchical clustering of individual LBAs into the ELIMA.score resulted in a highly significant correlation with overall survival, thereby bolstering evidence for the additive value of using multiple LBAs. Computation of mutual information indicated that none of the LBAs is independent of the others, but the ability of a single LBA to describe the others is rather limited—only CTC gDNA could partially describe the other three LBAs. SVD revealed that the strongest singular vectors originate from all four LBAs, but a majority originated from CTC gDNA. After k-means clustering of patients based on parameters of all four LBAs, the graph-theoretic analysis revealed CTC ERBB2 variants only in patients belonging to one particular cluster. Conclusions The additional benefits of using all four LBAs were objectively demonstrated in this pilot study, which also indicated a relative dominance of CTC gDNA over the other LBAs. Consequently, a multi-parametric liquid biopsy approach deconvolutes the genomic and transcriptomic complexity and should be considered in clinical practice.

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“…Considering the high accessibility and non-invasiveness of blood sampling, bloodbased predictive and prognostic models are expanding in the clinically relevant PCa research. To this end, Hofmann et al described a new multi-analyte assay, including CTCs enumeration and characterisation by mRNA-based in situ padlock probe technology, mRNA expression analysis of androgen receptor splice variant 7 (AR-V7), androgen receptor full length (AR-FL), and kallikrein related peptidase 3 (KLK3) transcripts from whole blood lysates by RT-qPCR, and detection of AR amplification by plasma-Seq [141].…”

Section: Liquid Biopsy Biomarker Panels For Pca Prediction Prognosis and Patient Stratification: Status Quo And Outlookmentioning

confidence: 99%

Systemic Effects Reflected in Specific Biomarker Patterns Are Instrumental for the Paradigm Change in Prostate Cancer Management: A Strategic Paper

Golubnitschaja

Kubatka

Mazuráková

et al. 2022

Cancers

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Prostate cancer (PCa) is reported as the most common malignancy and second leading cause of death in America. In Europe, PCa is considered the leading type of tumour in 28 European countries. The costs of treating PCa are currently increasing more rapidly than those of any other cancer. Corresponding economic burden is enormous, due to an overtreatment of slowly developing disease on one hand and underestimation/therapy resistance of particularly aggressive PCa subtypes on the other hand. The incidence of metastatic PCa is rapidly increasing that is particularly characteristic for young adults. PCa is a systemic multi-factorial disease resulting from an imbalanced interplay between risks and protective factors. Sub-optimal behavioural patterns, abnormal stress reactions, imbalanced antioxidant defence, systemic ischemia and inflammation, mitochondriopathies, aberrant metabolic pathways, gene methylation and damage to DNA, amongst others, are synergistically involved in pathomechanisms of PCa development and progression. To this end, PCa-relevant systemic effects are reflected in liquid biopsies such as blood patterns which are instrumental for predictive diagnostics, targeted prevention and personalisation of medical services (PPPM / 3P medicine) as a new paradigm in the overall PCa management. This strategic review article highlights systemic effects in prostate cancer development and progression, demonstrates evident challenges in PCa management and provides expert recommendations in the framework of 3P medicine.

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A Multi-Analyte Approach for Improved Sensitivity of Liquid Biopsies in Prostate Cancer

Cited by 24 publications

References 55 publications

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis

Integrative statistical analyses of multiple liquid biopsy analytes in metastatic breast cancer

Systemic Effects Reflected in Specific Biomarker Patterns Are Instrumental for the Paradigm Change in Prostate Cancer Management: A Strategic Paper

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