Grading Breast Cancer Tissues Using Molecular Portraits

Abstract

Tumor progression and prognosis in breast cancer patients are difficult to assess using current clinical and laboratory parameters, where a pathological grading is indicative of tumor aggressiveness. This grading is based on assessments of nuclear grade, tubule formation, and mitotic rate. We report here the first protein signatures associated with histological grades of breast cancer, determined using a novel affinity proteomics approach. We profiled 52 breast cancer tissue samples by combining nine antibodies and label-free LC-MS/MS, which generated detailed quantified proteomic maps representing 1,388 proteins. The results showed that we could define in-depth molecular portraits of histologically graded breast cancer tumors. Consequently, a 49-plex candidate tissue protein signature was defined that discriminated between histological grades 1, 2, and 3 of breast cancer tumors with high accuracy. Highly biologically relevant proteins were identified, and the differentially expressed proteins indicated further support for the current hypothesis regarding remodeling of the tumor microenvironment during tumor progression. The protein signature was corroborated using meta-analysis of transcriptional profiling data from an independent patient cohort. In addition, the potential for using the markers to estimate the likelihood of long-term metastasis-free survival was also indicated. Taken together, these molecular portraits could pave the way for improved classification and prognostication of breast cancer.

Tumor tissue protein signatures reflect histological grade of breast cancer

“…This work indicated a candidate 49-plex protein signature [24], refined and extended to a tentative 21-plex peptide signature (Olsson et al, submitted), for discriminating between histological grade 1,2 and 3 classified breast cancer, and for outlining the heterogeneity among grade 2 tumors. Importantly, these candidate biomarker signatures are completely different from the biomarker panels presented in this study, but they were found to provide similar biological information.…”

Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer

“…Therefore, proteomics has emerged as an integral part of modern biomedicine. For example, proteomics tools have been used for both cancer diagnosis and therapy selection as well as for researching the underlying mechanisms of disease pathogenesis and progression 12–14 . Specifically, one recent proteomic-based breast cancer study uncovered clinically distinct protein signatures for different histologically graded tumors 12 .…”

“…For example, proteomics tools have been used for both cancer diagnosis and therapy selection as well as for researching the underlying mechanisms of disease pathogenesis and progression 12–14 . Specifically, one recent proteomic-based breast cancer study uncovered clinically distinct protein signatures for different histologically graded tumors 12 . Another study developed a triple-negative breast cancer-specific protein profile 13 and a study by Tyanova et al characterised functional differences between different breast cancer subtypes 14 .…”

A Novel Strategy to Investigate Tissue‐Secreted Tumor Microenvironmental Proteins in Serum toward Development of Breast Cancer Early Diagnosis Biomarker Signature

“…These patients are mostly diagnosed with node positive disease, larger tumor size (T3/T4), undifferentiated tumor grade 3 (70%), minimal level of hormone receptor positivity, and overall poorer prognosis and survival . Prognosis prediction and treatment decision depend on the conventional histopathological tests, which often fail for discrimination of risk group and early diagnosis …”