Monitoring Radiotherapeutic Response in Prostate Cancer Patients Using High Throughput FTIR Spectroscopy of Liquid Biopsies

Radiation therapy (RT) is used to treat approximately 50% of all cancer patients. However, RT causes a wide range of adverse late effects that can affect a patient’s quality of life. There are currently no predictive assays in clinical use to identify patients at risk of normal tissue radiation toxicity. This study aimed to investigate the potential of Fourier transform infrared (FTIR) spectroscopy for monitoring radiotherapeutic response. Blood plasma was acquired from 53 prostate cancer patients at five different time points: prior to treatment, after hormone treatment, at the end of radiotherapy, two months post radiotherapy and eight months post radiotherapy. FTIR spectra were recorded from plasma samples at all time points and the data was analysed using MATLAB software. Discrimination was observed between spectra recorded at baseline versus follow up time points, as well as between spectra from patients showing minimal and severe acute and late toxicity using principal component analysis. A partial least squares discriminant analysis model achieved sensitivity and specificity rates ranging from 80% to 99%. This technology may have potential to monitor radiotherapeutic response in prostate cancer patients using non-invasive blood plasma samples and could lead to individualised patient radiotherapy.

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Development of a high throughput (HT) Raman spectroscopy method for rapid screening of liquid blood plasma from prostate cancer patients

The Analyst ◽

10.1039/c6an02100j ◽

2017 ◽

Vol 142 (8) ◽

pp. 1216-1226 ◽

Cited By ~ 26

Author(s):

Dinesh K. R. Medipally ◽

Adrian Maguire ◽

Jane Bryant ◽

John Armstrong ◽

Mary Dunne ◽

...

Keyword(s):

Prostate Cancer ◽

Raman Spectroscopy ◽

Blood Plasma ◽

Cancer Patients ◽

High Throughput ◽

Accurate Diagnosis ◽

Spectroscopy Method ◽

Rapid Screening ◽

Plasma Samples

High throughput Raman spectroscopy method for rapid and accurate diagnosis of prostate cancer using liquid plasma samples.

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Hydrolysis of ATP, ADP, and AMP is increased in blood plasma of prostate cancer patients

Purinergic Signalling ◽

10.1007/s11302-018-9642-3 ◽

2019 ◽

Vol 15 (1) ◽

pp. 95-105 ◽

Cited By ~ 4

Author(s):

Carla Fernanda Furtado Gardani ◽

Angélica Regina Cappellari ◽

Julia Brandt de Souza ◽

Bruna Tertuliano da Silva ◽

Paula Engroff ◽

...

Keyword(s):

Prostate Cancer ◽

Blood Plasma ◽

Cancer Patients ◽

Hydrolysis Of ◽

In Blood Plasma

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Glycans as Biomarkers in Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20061389 ◽

2019 ◽

Vol 20 (6) ◽

pp. 1389 ◽

Cited By ~ 18

Author(s):

Emma Scott ◽

Jennifer Munkley

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Liquid Biopsies ◽

Multifaceted Approach ◽

Disease Biomarkers ◽

High Profile ◽

Psa Testing ◽

Wide Range ◽

Multifocal Disease ◽

Core Fucosylation

Prostate cancer is the most commonly diagnosed malignancy in men, claiming over350,000 lives worldwide annually. Current diagnosis relies on prostate-specific antigen (PSA)testing, but this misses some aggressive tumours, and leads to the overtreatment of non-harmfuldisease. Hence, there is an urgent unmet clinical need to identify new diagnostic and prognosticbiomarkers. As prostate cancer is a heterogeneous and multifocal disease, it is likely that multiplebiomarkers will be needed to guide clinical decisions. Fluid-based biomarkers would be ideal, andattention is now turning to minimally invasive liquid biopsies, which enable the analysis oftumour components in patient blood or urine. Effective diagnostics using liquid biopsies willrequire a multifaceted approach, and a recent high-profile review discussed combining multipleanalytes, including changes to the tumour transcriptome, epigenome, proteome, and metabolome.However, the concentration on genomics-based paramaters for analysing liquid biopsies ispotentially missing a goldmine. Glycans have shown huge promise as disease biomarkers, anddata suggests that integrating biomarkers across multi-omic platforms (including changes to theglycome) can improve the stratification of patients with prostate cancer. A wide range ofalterations to glycans have been observed in prostate cancer, including changes to PSAglycosylation, increased sialylation and core fucosylation, increased O-GlcNacylation, theemergence of cryptic and branched N-glyans, and changes to galectins and proteoglycans. In thisreview, we discuss the huge potential to exploit glycans as diagnostic and prognostic biomarkersfor prostate cancer, and argue that the inclusion of glycans in a multi-analyte liquid biopsy test forprostate cancer will help maximise clinical utility.

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Prostate Cancer Patients with Late Radiation Toxicity Exhibit Reduced Expression of Genes Involved in DNA Double-Strand Break Repair and Homologous Recombination

Cancer Research ◽

10.1158/0008-5472.can-16-1966 ◽

2017 ◽

Vol 77 (6) ◽

pp. 1485-1491 ◽

Cited By ~ 7

Author(s):

Bregje van Oorschot ◽

Lon Uitterhoeve ◽

Ilja Oomen ◽

Rosemarie ten Cate ◽

Jan Paul Medema ◽

...

Keyword(s):

Prostate Cancer ◽

Homologous Recombination ◽

Cancer Patients ◽

Strand Break ◽

Double Strand Break ◽

Double Strand Break Repair ◽

Radiation Toxicity ◽

Expression Of Genes ◽

Dna Double Strand Break ◽

Break Repair

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hsa_circ_0001275 Is One of a Number of circRNAs Dysregulated in Enzalutamide Resistant Prostate Cancer and Confers Enzalutamide Resistance In Vitro

Cancers ◽

10.3390/cancers13246383 ◽

2021 ◽

Vol 13 (24) ◽

pp. 6383

Author(s):

Marvin C. J. Lim ◽

Anne-Marie Baird ◽

John Greene ◽

Ciara McNevin ◽

Karine Ronan ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Line ◽

Quantitative Polymerase Chain Reaction ◽

Statistical Significance ◽

Control Cell ◽

Plasma Samples ◽

Castration Resistant Prostate Cancer ◽

Liquid Biopsies ◽

Control Cell Line

Background: Enzalutamide is part of the treatment regimen for metastatic castration-resistant prostate cancer (MCRPC). However, both intrinsic and acquired resistance to the drug remain substantial clinical quandaries. circRNAs, a novel type of non-coding RNA, have been identified in a number of cancers including prostate cancer and have been associated with cancer development and progression. circRNAs have shown great potential as clinically useful blood-based ‘liquid biopsies’ and as therapeutic targets in prostate cancer. The aim of this study was to examine the role of circRNA transcripts in enzalutamide-resistant prostate cancer cells and assess their utility as biomarkers. Methods: An isogenic cell line model of enzalutamide resistance was subjected to circRNA microarray profiling. Several differentially expressed circRNAs, along with their putative parental genes were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). circRNAs of interest were stably overexpressed in the control cell line and drug sensitivity was assessed using an ELISA-based proliferation assay. The candidate circRNA, hsa_circ_0001275, was measured in patient plasma samples using RT-droplet digital PCR (RT-ddPCR). Results: hsa_circ_0001275 and its parental gene, PLCL2, were significantly up-regulated in strongly resistant clones vs. control (p < 0.05). Overexpression of hsa_circ_0001275 in the control cell line resulted in increased resistance to enzalutamide (p < 0.05). While RT-ddPCR analysis of hsa_circ_0001275 expression in plasma samples of 44 clinical trial participants showed a trend that mirrored the stages of disease activity (as defined by PSA level), the association did not reach statistical significance. Conclusions: Our data suggest that increased levels of hsa_circ_0001275 contribute to enzalutamide resistance. hsa_circ_0001275 plasma expression showed a trend that mirrors the PSA level at specific disease time points, indicating that circRNAs mirror disease recurrence and burden and may be associated with enzalutamide resistance.

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Detection of AR-V7 in Liquid Biopsies of Castrate Resistant Prostate Cancer Patients: A Comparison of AR-V7 Analysis in Circulating Tumor Cells, Circulating Tumor RNA and Exosomes

Cells ◽

10.3390/cells8070688 ◽

2019 ◽

Vol 8 (7) ◽

pp. 688 ◽

Cited By ~ 8

Author(s):

Mohammed Nimir ◽

Yafeng Ma ◽

Sarah A. Jeffreys ◽

Thomas Opperman ◽

Francis Young ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Digital Pcr ◽

Liquid Biopsies ◽

Tumor Biopsy ◽

Highly Sensitive ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

Detection of androgen receptor (AR) variant 7 (AR-V7) is emerging as a clinically important biomarker in castrate resistant prostate cancer (CRPC). Detection is possible from tumor tissue, which is often inaccessible in the advanced disease setting. With recent progress in detecting AR-V7 in circulating tumor cells (CTCs), circulating tumor RNA (ctRNA) and exosomes from prostate cancer patients, liquid biopsies have emerged as an alternative to tumor biopsy. Therefore, it is important to clarify whether these approaches differ in sensitivity in order to achieve the best possible biomarker characterization for the patient. In this study, blood samples from 44 prostate cancer patients were processed for CTCs and ctRNA with subsequent AR-V7 testing, while exosomal RNA was isolated from 16 samples and tested. Detection of AR and AR-V7 was performed using a highly sensitive droplet digital PCR-based assay. AR and AR-V7 RNA were detectable in CTCs, ctRNA and exosome samples. AR-V7 detection from CTCs showed higher sensitivity and has proven specificity compared to detection from ctRNA and exosomes. Considering that CTCs are almost always present in the advanced prostate cancer setting, CTC samples should be considered the liquid biopsy of choice for the detection of this clinically important biomarker.

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