Quantitative SWATH-based proteomic profiling of urine for the identification of endometrial cancer biomarkers in symptomatic women
Research output: Contribution to journal › Article › peer-review
Standard Standard
In: British Journal of Cancer, Vol. 128, No. 9, 18.05.2023, p. 1723-1732.
Research output: Contribution to journal › Article › peer-review
HarvardHarvard
APA
CBE
MLA
VancouverVancouver
Author
RIS
TY - JOUR
T1 - Quantitative SWATH-based proteomic profiling of urine for the identification of endometrial cancer biomarkers in symptomatic women
AU - Njoku, Kelechi
AU - Pierce, Andrew
AU - Geary, Bethany
AU - Campbell, Amy E.
AU - Kelsall, Janet
AU - Reed, Rachel
AU - Armit, Alexander
AU - Da Sylva, Rachel
AU - Zhang, Liqun
AU - Agnew, Heather
AU - Baricevic-Jones, Ivona
AU - Chiasserini, Davide
AU - Whetton, Anthony D.
AU - Crosbie, Emma J.
N1 - © 2023. The Author(s).
PY - 2023/5/18
Y1 - 2023/5/18
N2 - BACKGROUND: A non-invasive endometrial cancer detection tool that can accurately triage symptomatic women for definitive testing would improve patient care. Urine is an attractive biofluid for cancer detection due to its simplicity and ease of collection. The aim of this study was to identify urine-based proteomic signatures that can discriminate endometrial cancer patients from symptomatic controls.METHODS: This was a prospective case-control study of symptomatic post-menopausal women (50 cancers, 54 controls). Voided self-collected urine samples were processed for mass spectrometry and run using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning techniques were used to identify important discriminatory proteins, which were subsequently combined in multi-marker panels using logistic regression.RESULTS: The top discriminatory proteins individually showed moderate accuracy (AUC > 0.70) for endometrial cancer detection. However, algorithms combining the most discriminatory proteins performed well with AUCs > 0.90. The best performing diagnostic model was a 10-marker panel combining SPRR1B, CRNN, CALML3, TXN, FABP5, C1RL, MMP9, ECM1, S100A7 and CFI and predicted endometrial cancer with an AUC of 0.92 (0.96-0.97). Urine-based protein signatures showed good accuracy for the detection of early-stage cancers (AUC 0.92 (0.86-0.9)).CONCLUSION: A patient-friendly, urine-based test could offer a non-invasive endometrial cancer detection tool in symptomatic women. Validation in a larger independent cohort is warranted.
AB - BACKGROUND: A non-invasive endometrial cancer detection tool that can accurately triage symptomatic women for definitive testing would improve patient care. Urine is an attractive biofluid for cancer detection due to its simplicity and ease of collection. The aim of this study was to identify urine-based proteomic signatures that can discriminate endometrial cancer patients from symptomatic controls.METHODS: This was a prospective case-control study of symptomatic post-menopausal women (50 cancers, 54 controls). Voided self-collected urine samples were processed for mass spectrometry and run using sequential window acquisition of all theoretical mass spectra (SWATH-MS). Machine learning techniques were used to identify important discriminatory proteins, which were subsequently combined in multi-marker panels using logistic regression.RESULTS: The top discriminatory proteins individually showed moderate accuracy (AUC > 0.70) for endometrial cancer detection. However, algorithms combining the most discriminatory proteins performed well with AUCs > 0.90. The best performing diagnostic model was a 10-marker panel combining SPRR1B, CRNN, CALML3, TXN, FABP5, C1RL, MMP9, ECM1, S100A7 and CFI and predicted endometrial cancer with an AUC of 0.92 (0.96-0.97). Urine-based protein signatures showed good accuracy for the detection of early-stage cancers (AUC 0.92 (0.86-0.9)).CONCLUSION: A patient-friendly, urine-based test could offer a non-invasive endometrial cancer detection tool in symptomatic women. Validation in a larger independent cohort is warranted.
KW - Humans
KW - Female
KW - Biomarkers, Tumor
KW - Case-Control Studies
KW - Proteomics/methods
KW - Biomarkers
KW - Mass Spectrometry/methods
KW - Endometrial Neoplasms/diagnosis
KW - Fatty Acid-Binding Proteins
KW - Extracellular Matrix Proteins
U2 - 10.1038/s41416-022-02139-0
DO - 10.1038/s41416-022-02139-0
M3 - Article
C2 - 36807337
VL - 128
SP - 1723
EP - 1732
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 9
ER -