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Wark, L., Klonisch, T., Awe, J., LeClerc, C., Dyck, B., Quon, H. & Mai, S. (2017). Dynamics of three-dimensional telomere profiles of circulating tumor cells in patients with high-risk prostate cancer who are undergoing androgen deprivation and radiation therapies. Urologic Oncology, 35(3), 112.e1-112.e11
Open this publication in new window or tab >>Dynamics of three-dimensional telomere profiles of circulating tumor cells in patients with high-risk prostate cancer who are undergoing androgen deprivation and radiation therapies
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2017 (English)In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 35, no 3, p. 112.e1-112.e11Article in journal (Refereed) Published
Abstract [en]

Introduction: Accurate assessment and monitoring of the therapeutic efficacy of locally advanced prostate cancer remains a major clinical challenge. Contrary to prostate biopsies, circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling and could serve as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate and enumerate CTCs from the blood of 20 patients with high-risk (any one of cT3, Gleason 810, or prostate-specific antigen>20 ng/ml), nonmetastatic, and treatment-naive prostate cancer before and after androgen deprivation therapy (ADT) and radiation therapy (RT).

Materials and methods: We performed 3D telomere-specific quantitative fluorescence in situ hybridization on isolated CTCs to determine 3D telomere profiles for each patient before and throughout the course of both ADT and RT.

Results: Based on the distinct 3D telomere signatures of CTC before treatment, patients were divided into 3 groups. ADT and RT resulted in distinct changes in 3D telomere signatures of CTCs, which were unique for each of the 3 patient groups.

Conclusion: The ability of 3D telomere analysis of CTCs to identify disease heterogeneity among a clinically homogeneous group of patients, which reveals differences in therapeutic responses, provides a new opportunity for better treatment monitoring and management of patients with high-risk prostate cancer. 

Keywords
High-risk prostate cancer, Telomeres, Circulating tumor cells, Biomarkers
National Category
Clinical Medicine
Identifiers
urn:nbn:se:his:diva-13794 (URN)10.1016/j.urolonc.2016.10.018 (DOI)000401092000007 ()27956006 (PubMedID)2-s2.0-85008154395 (Scopus ID)
Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2018-10-31Bibliographically approved
Awe, J. A., Saranchuk, J., Drachenberg, D. & Mai, S. (2017). Filtration-based enrichment of circulating tumor cells from all prostate cancer risk groups. Urologic Oncology, 35(5), 300-309
Open this publication in new window or tab >>Filtration-based enrichment of circulating tumor cells from all prostate cancer risk groups
2017 (English)In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 35, no 5, p. 300-309Article in journal (Refereed) Published
Abstract [en]

Objective: To combine circulating tumor cell (CTC) isolation by filtration and immunohistochemistry to investigate the presence of CTCs in low, intermediate, and high-risk prostate cancer (PCa). CTCs isolated from these risk groups stained positive for both cytokeratin and androgen receptors, but negative for CD45.

Patients and methods: Blood samples from 41 biopsy confirmed patients with PCa at different clinical stages such as low, intermediate, and high risk were analyzed. The samples were processed with the ScreenCell filtration device and PCa CTCs were captured for all patients. The isolated CTCs were confirmed PCa CTCs by the presence of androgen receptors and cytokeratins 8, 18, and 19 that occurred in the absence of CD45 positivity. PCa CTC nuclear sizes were measured using the TeloView program.

Results: The filtration-based isolation method used permitted the measurement of the average nuclear size of the captured CTCs. CTCs were identified by immunohistochemistry in low, intermediate, and high-risk groups of patients with PCa.

Conclusion: CTCs may be found in all stages of PCa. These CTCs can be used to determine the level of genomic instability at any stage of PCa; this will, in the future, enable personalized patient management. 

Keywords
Prostate cancer, Circulating tumor cells, Androgen receptors, Cytokeratin, Filter isolation
National Category
Clinical Medicine
Identifiers
urn:nbn:se:his:diva-13792 (URN)10.1016/j.urolonc.2016.12.008 (DOI)000401095200019 ()28202223 (PubMedID)2-s2.0-85011983770 (Scopus ID)
Available from: 2017-06-20 Created: 2017-06-20 Last updated: 2018-10-31Bibliographically approved
Horning, A. M., Awe, J. A., Wang, C.-M., Liu, J., Lai, Z., Wang, V. Y., . . . Huang, T.-M. H. (2015). DNA Methylation Screening of Primary Prostate Tumors Identifies SRD5A2 and CYP11A1 as Candidate Markers for Assessing Risk of Biochemical Recurrence. The Prostate, 75(15), 1790-1801
Open this publication in new window or tab >>DNA Methylation Screening of Primary Prostate Tumors Identifies SRD5A2 and CYP11A1 as Candidate Markers for Assessing Risk of Biochemical Recurrence
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2015 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 75, no 15, p. 1790-1801Article in journal (Refereed) Published
Abstract [en]

BACKGROUND. Altered DNA methylation in CpG islands of gene promoters has been implicated in prostate cancer (PCa) progression and can be used to predict disease outcome. In this study, we determine whether methylation changes of androgen biosynthesis pathway (ABP)-related genes in patients' plasma cell-free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR). METHODS. Methyl-binding domain capture sequencing (MBDCap-seq) was used to identify differentially methylated regions (DMRs) in primary tumors of patients who subsequently developed BCR or not, respectively. Methylation pyrosequencing of candidate loci was validated in cfDNA samples of 86 PCa patients taken at and/or post-radical prostatectomy (RP) using univariate and multivariate prediction analyses. RESULTS. Putative DMRs in 13 of 30 ABP-related genes were found between tumors of BCR (n = 12) versus no evidence of disease (NED) (n = 15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci-SRD5A2 and CYP11A1, which also correlated with their decreased expression, in tumors with subsequent BCR development. Their aberrant cfDNA methylation was also associated with detectable levels of PSA taken after patients' post-RP. Multivariate analysis of the change in cfDNA methylation at all of CpG sites measured along with patient's treatment history predicted if a patient will develop BCR with 77.5% overall accuracy. CONCLUSIONS. Overall, increased DNA methylation of SRD5A2 and CYP11A1 related to androgen biosynthesis functions may play a role in BCR after patients' RP. The correlation between aberrant cfDNA methylation and detectable PSA in post-RP further suggests their utility as predictive markers for PCa recurrence. (C) 2015 Wiley Periodicals, Inc.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
Keywords
prostate cancer, DNA methylation, plasma, biochemical recurrence
National Category
Medical Genetics Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:his:diva-13580 (URN)10.1002/pros.23052 (DOI)000363219200013 ()26332453 (PubMedID)2-s2.0-84942830759 (Scopus ID)
Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2019-02-19Bibliographically approved
Awe, J. A., Xu, M. C., Wechsler, J., Benali-Furet, N., Cayre, Y. E., Saranchuk, J., . . . Mai, S. (2013). Three-Dimensional Telomeric Analysis of Isolated Circulating Tumor Cells (CTCs) Defines CTC Subpopulations. Translational Oncology, 6(1), 51-65
Open this publication in new window or tab >>Three-Dimensional Telomeric Analysis of Isolated Circulating Tumor Cells (CTCs) Defines CTC Subpopulations
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2013 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 6, no 1, p. 51-65Article in journal (Refereed) Published
Abstract [en]

Circulating tumor cells (CTCs) have been identified with the potential to serve as suitable biomarkers for tumor stage and progression, but the availability of effective isolation technique(s) coupled with detailed molecular characterization have been the challenges encountered in making CTCs clinically relevant. For the first time, we combined isolation of CTCs using the ScreenCell filtration technique with quantitative analysis of CTC telomeres by TeloView. This resulted in the identification and molecular characterization of different subpopulations of CTCs in the same patient. Three-dimensional (3D) telomeric analysis was carried out on isolated CTCs of 19 patients that consisted of four different tumor types, namely, prostate, colon, breast, melanoma, and one lung cancer cell line. With telomeric analysis of the filter-isolated CTCs, the level of chromosomal instability (CIN) of the CTCs can be determined. Our study shows that subpopulations of CTCs can be identified on the basis of their 3D telomeric properties.

Place, publisher, year, edition, pages
Neoplasia Press, 2013
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-8851 (URN)10.1593/tlo.12361 (DOI)000318620200008 ()23418617 (PubMedID)2-s2.0-84874727652 (Scopus ID)
Available from: 2014-02-14 Created: 2014-02-14 Last updated: 2019-02-19Bibliographically approved
Organisations
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ORCID iD: ORCID iD iconorcid.org/0000-0002-4524-0783

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