Detection and characterization of lung cancer using cell-free DNA fragmentomes
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Detection and characterization of lung cancer using cell-free DNA fragmentomes. / Mathios, Dimitrios; Johansen, Jakob Sidenius; Cristiano, Stephen; Medina, Jamie E.; Phallen, Jillian; Larsen, Klaus R.; Bruhm, Daniel C.; Niknafs, Noushin; Ferreira, Leonardo; Adleff, Vilmos; Chiao, Jia Yuee; Leal, Alessandro; Noe, Michael; White, James R.; Arun, Adith S.; Hruban, Carolyn; Annapragada, Akshaya V.; Jensen, Sarah Østrup; Ørntoft, Mai Britt Worm; Madsen, Anders Husted; Carvalho, Beatriz; de Wit, Meike; Carey, Jacob; Dracopoli, Nicholas C.; Maddala, Tara; Fang, Kenneth C.; Hartman, Anne Renee; Forde, Patrick M.; Anagnostou, Valsamo; Brahmer, Julie R.; Fijneman, Remond J.A.; Nielsen, Hans Jørgen; Meijer, Gerrit A.; Andersen, Claus Lindbjerg; Mellemgaard, Anders; Bojesen, Stig E.; Scharpf, Robert B.; Velculescu, Victor E.
I: Nature Communications, Bind 12, Nr. 1, 5060, 12.2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Detection and characterization of lung cancer using cell-free DNA fragmentomes
AU - Mathios, Dimitrios
AU - Johansen, Jakob Sidenius
AU - Cristiano, Stephen
AU - Medina, Jamie E.
AU - Phallen, Jillian
AU - Larsen, Klaus R.
AU - Bruhm, Daniel C.
AU - Niknafs, Noushin
AU - Ferreira, Leonardo
AU - Adleff, Vilmos
AU - Chiao, Jia Yuee
AU - Leal, Alessandro
AU - Noe, Michael
AU - White, James R.
AU - Arun, Adith S.
AU - Hruban, Carolyn
AU - Annapragada, Akshaya V.
AU - Jensen, Sarah Østrup
AU - Ørntoft, Mai Britt Worm
AU - Madsen, Anders Husted
AU - Carvalho, Beatriz
AU - de Wit, Meike
AU - Carey, Jacob
AU - Dracopoli, Nicholas C.
AU - Maddala, Tara
AU - Fang, Kenneth C.
AU - Hartman, Anne Renee
AU - Forde, Patrick M.
AU - Anagnostou, Valsamo
AU - Brahmer, Julie R.
AU - Fijneman, Remond J.A.
AU - Nielsen, Hans Jørgen
AU - Meijer, Gerrit A.
AU - Andersen, Claus Lindbjerg
AU - Mellemgaard, Anders
AU - Bojesen, Stig E.
AU - Scharpf, Robert B.
AU - Velculescu, Victor E.
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.
AB - Non-invasive approaches for cell-free DNA (cfDNA) assessment provide an opportunity for cancer detection and intervention. Here, we use a machine learning model for detecting tumor-derived cfDNA through genome-wide analyses of cfDNA fragmentation in a prospective study of 365 individuals at risk for lung cancer. We validate the cancer detection model using an independent cohort of 385 non-cancer individuals and 46 lung cancer patients. Combining fragmentation features, clinical risk factors, and CEA levels, followed by CT imaging, detected 94% of patients with cancer across stages and subtypes, including 91% of stage I/II and 96% of stage III/IV, at 80% specificity. Genome-wide fragmentation profiles across ~13,000 ASCL1 transcription factor binding sites distinguished individuals with small cell lung cancer from those with non-small cell lung cancer with high accuracy (AUC = 0.98). A higher fragmentation score represented an independent prognostic indicator of survival. This approach provides a facile avenue for non-invasive detection of lung cancer.
U2 - 10.1038/s41467-021-24994-w
DO - 10.1038/s41467-021-24994-w
M3 - Journal article
C2 - 34417454
AN - SCOPUS:85113257362
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5060
ER -
ID: 286314755