Cell-free DNA concentration and fragment size as a biomarker for prostate cancer
Abstract Prostate cancer is the most commonly diagnosed neoplasm in American men. Although existing biomarkers may detect localized prostate cancer, additional strategies are necessary for improving detection and identifying aggressive disease that may require further intervention. One promising, mi...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/3bda01622d5a48dca54ff3356e239cb8 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:3bda01622d5a48dca54ff3356e239cb8 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:3bda01622d5a48dca54ff3356e239cb82021-12-02T13:20:22ZCell-free DNA concentration and fragment size as a biomarker for prostate cancer10.1038/s41598-021-84507-z2045-2322https://doaj.org/article/3bda01622d5a48dca54ff3356e239cb82021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84507-zhttps://doaj.org/toc/2045-2322Abstract Prostate cancer is the most commonly diagnosed neoplasm in American men. Although existing biomarkers may detect localized prostate cancer, additional strategies are necessary for improving detection and identifying aggressive disease that may require further intervention. One promising, minimally invasive biomarker is cell-free DNA (cfDNA), which consist of short DNA fragments released into circulation by dying or lysed cells that may reflect underlying cancer. Here we investigated whether differences in cfDNA concentration and cfDNA fragment size could improve the sensitivity for detecting more advanced and aggressive prostate cancer. This study included 268 individuals: 34 healthy controls, 112 men with localized prostate cancer who underwent radical prostatectomy (RP), and 122 men with metastatic castration-resistant prostate cancer (mCRPC). Plasma cfDNA concentration and fragment size were quantified with the Qubit 3.0 and the 2100 Bioanalyzer. The potential relationship between cfDNA concentration or fragment size and localized or mCRPC prostate cancer was evaluated with descriptive statistics, logistic regression, and area under the curve analysis with cross-validation. Plasma cfDNA concentrations were elevated in mCRPC patients in comparison to localized disease (OR5ng/mL = 1.34, P = 0.027) or to being a control (OR5ng/mL = 1.69, P = 0.034). Decreased average fragment size was associated with an increased risk of localized disease compared to controls (OR5bp = 0.77, P = 0.0008). This study suggests that while cfDNA concentration can identify mCRPC patients, it is unable to distinguish between healthy individuals and patients with localized prostate cancer. In addition to PSA, average cfDNA fragment size may be an alternative that can differentiate between healthy individuals and those with localized disease, but the low sensitivity and specificity results in an imperfect diagnostic marker. While quantification of cfDNA may provide a quick, cost-effective approach to help guide treatment decisions in advanced disease, its use is limited in the setting of localized prostate cancer.Emmalyn ChenClinton L. CarioLancelote LeongKaren LopezCésar P. MárquezCarissa ChuPatricia S. LiErica OropezaImelda TenggaraJanet CowanJeffry P. SimkoJune M. ChanTerence FriedlanderAlexander W. WyattRahul AggarwalPamela L. ParisPeter R. CarrollFelix FengJohn S. WitteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Emmalyn Chen Clinton L. Cario Lancelote Leong Karen Lopez César P. Márquez Carissa Chu Patricia S. Li Erica Oropeza Imelda Tenggara Janet Cowan Jeffry P. Simko June M. Chan Terence Friedlander Alexander W. Wyatt Rahul Aggarwal Pamela L. Paris Peter R. Carroll Felix Feng John S. Witte Cell-free DNA concentration and fragment size as a biomarker for prostate cancer |
| description |
Abstract Prostate cancer is the most commonly diagnosed neoplasm in American men. Although existing biomarkers may detect localized prostate cancer, additional strategies are necessary for improving detection and identifying aggressive disease that may require further intervention. One promising, minimally invasive biomarker is cell-free DNA (cfDNA), which consist of short DNA fragments released into circulation by dying or lysed cells that may reflect underlying cancer. Here we investigated whether differences in cfDNA concentration and cfDNA fragment size could improve the sensitivity for detecting more advanced and aggressive prostate cancer. This study included 268 individuals: 34 healthy controls, 112 men with localized prostate cancer who underwent radical prostatectomy (RP), and 122 men with metastatic castration-resistant prostate cancer (mCRPC). Plasma cfDNA concentration and fragment size were quantified with the Qubit 3.0 and the 2100 Bioanalyzer. The potential relationship between cfDNA concentration or fragment size and localized or mCRPC prostate cancer was evaluated with descriptive statistics, logistic regression, and area under the curve analysis with cross-validation. Plasma cfDNA concentrations were elevated in mCRPC patients in comparison to localized disease (OR5ng/mL = 1.34, P = 0.027) or to being a control (OR5ng/mL = 1.69, P = 0.034). Decreased average fragment size was associated with an increased risk of localized disease compared to controls (OR5bp = 0.77, P = 0.0008). This study suggests that while cfDNA concentration can identify mCRPC patients, it is unable to distinguish between healthy individuals and patients with localized prostate cancer. In addition to PSA, average cfDNA fragment size may be an alternative that can differentiate between healthy individuals and those with localized disease, but the low sensitivity and specificity results in an imperfect diagnostic marker. While quantification of cfDNA may provide a quick, cost-effective approach to help guide treatment decisions in advanced disease, its use is limited in the setting of localized prostate cancer. |
| format |
article |
| author |
Emmalyn Chen Clinton L. Cario Lancelote Leong Karen Lopez César P. Márquez Carissa Chu Patricia S. Li Erica Oropeza Imelda Tenggara Janet Cowan Jeffry P. Simko June M. Chan Terence Friedlander Alexander W. Wyatt Rahul Aggarwal Pamela L. Paris Peter R. Carroll Felix Feng John S. Witte |
| author_facet |
Emmalyn Chen Clinton L. Cario Lancelote Leong Karen Lopez César P. Márquez Carissa Chu Patricia S. Li Erica Oropeza Imelda Tenggara Janet Cowan Jeffry P. Simko June M. Chan Terence Friedlander Alexander W. Wyatt Rahul Aggarwal Pamela L. Paris Peter R. Carroll Felix Feng John S. Witte |
| author_sort |
Emmalyn Chen |
| title |
Cell-free DNA concentration and fragment size as a biomarker for prostate cancer |
| title_short |
Cell-free DNA concentration and fragment size as a biomarker for prostate cancer |
| title_full |
Cell-free DNA concentration and fragment size as a biomarker for prostate cancer |
| title_fullStr |
Cell-free DNA concentration and fragment size as a biomarker for prostate cancer |
| title_full_unstemmed |
Cell-free DNA concentration and fragment size as a biomarker for prostate cancer |
| title_sort |
cell-free dna concentration and fragment size as a biomarker for prostate cancer |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/3bda01622d5a48dca54ff3356e239cb8 |
| work_keys_str_mv |
AT emmalynchen cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT clintonlcario cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT lanceloteleong cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT karenlopez cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT cesarpmarquez cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT carissachu cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT patriciasli cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT ericaoropeza cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT imeldatenggara cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT janetcowan cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT jeffrypsimko cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT junemchan cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT terencefriedlander cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT alexanderwwyatt cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT rahulaggarwal cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT pamelalparis cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT peterrcarroll cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT felixfeng cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer AT johnswitte cellfreednaconcentrationandfragmentsizeasabiomarkerforprostatecancer |
| _version_ |
1718393204225605632 |