A Validation Study of a Multiple Reaction Monitoring-Based Proteomic Assay to Diagnose Breast Cancer

Abstract

PurposeCurrently, the standard screening tool for breast cancer is screening mammography. There have been many efforts to develop a blood-based diagnostic assay for breast cancer diagnosis; however, none have been approved for clinical use at this time. The purpose of this study was to determine the accuracy of a novel blood-based proteomic test for aiding breast cancer diagnosis in a relatively large cohort of cancer patients.MethodsA blood-based test using multiple reaction monitoring (MRM) measured by mass spectrometry to quantify 3 peptides (apolipoprotein C-1, carbonic anhydrase 1, and neural cell adhesion molecule L1-like protein) present in human plasma was investigated. A total of 1,129 blood samples from 575 breast cancer patients, 454 healthy controls, and 100 patients with other malignancies were used to verify and optimize the assay.ResultsThe diagnostic sensitivity, specificity, and accuracy of the MRM-based proteomic assay were 71.6%, 85.3%, and 77%, respectively; the area under the receiver operating characteristic curve was 0.8323. The proteomic assay did not demonstrate diagnostic accuracy in patients with other types of malignancies including thyroid, pancreatic, lung, and colon cancers. The diagnostic performance of the proteomic assay was not associated with the timing of blood sampling before or after anesthesia.ConclusionThe data demonstrated that an MRM-based proteomic assay that measures plasma levels of three specific peptides can be a useful tool for breast cancer screening and its accuracy is cancer-type specific.

Diagnostic performance improvement with combined use of proteomics biomarker assay and breast ultrasound

“…Thus, they suggested that their algorithm with higher performance in early stage breast cancers was bene cial for detecting breast cancers in the asymptomatic phase [33]. In a prior study from the same study group, total of 460 plasma samples, 228 from breast cancer patients and 232 from healthy controls, was used to validate their algorithm and reported diagnostic accuracy with AUC of 0.88 [31]. Mastocheck® was also useful in patients with dense breasts, showing increased sensitivity from 59.2% (mammography alone) to 93.0% (mammography and Mastocheck®) [32,33].…”

“…A previous study reported 0.0668 as an optimal cut-off value of Mastocheck® for breast cancer diagnosis, with a sensitivity and speci city of 67.0% and 82.0%, respectively. Further validation studies showed sensitivity and speci city of 71.6% and 85.3%, respectively, with the cut-off value mentioned above (31,32). Based on this, a positive result was de ned as a Mastocheck® value of ≥ 0.0668 and a negative result of < 0.0668 [32].…”

“…H-1807-057-957) and underwent bilateral whole-breast US within at least 6 months from the sampling period. The subgroup of this study population has been reported in previous studies [31][32][33]. Patients were excluded for the following reasons: undergone breast surgery within the previous 12 months, personal history of breast cancer, and no follow-up for at least 12 months to con rm the stability of the lesion.…”

“…However, the data on using liquid biopsy as a screening tool in breast cancer are limited [27][28][29][30]. According to a recent publication, a blood-based 3-protein signature derived from multiple reaction monitoring (MRM)-based proteomic assay showed sensitivity, speci city, and accuracy of 71.6 %, 85.3%, and 77.0%, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.83, which is speci c for breast cancers and no other types of malignancies including thyroid, pancreatic, lung, and colon cancers [31]. In addition, the results of a blood-based 3-protein signature alone were superior compared to that of only mammography, as interpreted by non-dedicated general radiologists; furthermore, the diagnostic performance was improved by using a combination of mammography and a blood-based 3-protein signature [32].…”

Targeted liquid chromatography‐tandem mass spectrometry analysis of proteins: Basic principles, applications, and perspectives

“…cerebrospinal fluid [131], urine [132][133][134], and formalin-fixed paraffinembedded (FFPE) samples [135][136][137]. These analyses have sought to quantify the protein biomarkers of breast cancer [21,[137][138][139][140], colorectal cancer [141][142][143][144][145], lung cancer [146][147][148][149], oral cancer [150,151], multiple sclerosis [131,152], cardiovascular diseases [153][154][155][156][157][158],…”