TY - JOUR
T1 - Selected reaction monitoring approach for validating peptide biomarkers
AU - Wang, Qing
AU - Zhang, Ming
AU - Tomita, Tyler
AU - Vogelstein, Joshua T.
AU - Zhou, Shibin
AU - Papadopoulos, Nickolas
AU - Kinzler, Kenneth W.
AU - Vogelstein, Bert
N1 - Funding Information:
ACKNOWLEDGMENTS. This work was supported by The Virginia and D. K. Ludwig Fund for Cancer Research, The Lustgarten Foundation for Pancreatic Cancer Research, The Conrad N. Hilton Foundation, and National Institutes of Health Grants P50-CA62924, CA06973, and GM07309.
PY - 2017/12/19
Y1 - 2017/12/19
N2 - We here describe a selected reaction monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate peptides were identified through this method, providing challenges for choosing and validating the small number of peptides that might prove diagnostically useful. To accomplish this validation, we used 2D chromatography coupled with SRM of candidate peptides. We applied this approach, called sequential analysis of fractionated eluates by SRM (SAFE-SRM), to plasma from cancer patients and discovered two peptides encoded by the peptidyl-prolyl cis-trans isomerase A (PPIA) gene whose abundance was increased in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels of at least one of these two peptides was detected in 43 (68.3%) of 63 women with ovarian cancer but in none of 50 healthy controls. In addition to providing a potential biomarker for ovarian cancer, this approach is generally applicable to the discovery of peptides characteristic of various disease states.
AB - We here describe a selected reaction monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate peptides were identified through this method, providing challenges for choosing and validating the small number of peptides that might prove diagnostically useful. To accomplish this validation, we used 2D chromatography coupled with SRM of candidate peptides. We applied this approach, called sequential analysis of fractionated eluates by SRM (SAFE-SRM), to plasma from cancer patients and discovered two peptides encoded by the peptidyl-prolyl cis-trans isomerase A (PPIA) gene whose abundance was increased in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels of at least one of these two peptides was detected in 43 (68.3%) of 63 women with ovarian cancer but in none of 50 healthy controls. In addition to providing a potential biomarker for ovarian cancer, this approach is generally applicable to the discovery of peptides characteristic of various disease states.
KW - Cancer diagnostics
KW - Clinical proteomics
KW - Peptide biomarker
KW - Plasma biomarker
KW - Selected reaction monitoring
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U2 - 10.1073/pnas.1712731114
DO - 10.1073/pnas.1712731114
M3 - Article
C2 - 29203663
AN - SCOPUS:85038882572
VL - 114
SP - 13519
EP - 13524
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 51
ER -