TY - JOUR
T1 - Using tears as a non-invasive source for early detection of breast cancer
AU - Daily, Anna
AU - Ravishankar, Prashanth
AU - Harms, Steve
AU - Klimberg, V. Suzanne
N1 - Funding Information:
Namida Lab Inc. is a privately funded company and provided funds for conducting this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AED and PR are employees of Namida Lab Inc. AED is an inventor on the patent and serves as the Vice President of Product Development and Innovation and owns shares of Namida Lab Inc. PR serves as the Research and Development Scientist at Namida Lab Inc. SH and VSK are on the clinical advisory board of Namida Lab Inc. The authors appreciate the work of the Proteomic Core Lab at University of Arkansas for Medical Sciences. We would also like to acknowledge the work of Kamila Kozlowski MD, Knoxville Comprehensive Breast Center, TN; LaNette Smith MD, Breast Surgery of Tulsa, OK; Brad Jensen MD, PeaceHealth Southwest, Vancouver, WA; Sheila Lynam PeaceHealth St. John Medical Center, Longview, WA for their assistance with the samples. We also appreciate the work by Christopher Ghast and Andy Mavromoustakos, University of Arkansas, for their statistical contributions; and the Proteomic core facility at UAMS Little Rock, AR for their support with Mass Spectrometry analysis.
Publisher Copyright:
Copyright: © 2022 Daily et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/4
Y1 - 2022/4
N2 - The changing expression levels of ocular proteins in response to systemic disease has been well established in literature. In this study, we examined the ocular proteome to identify protein biomarkers with altered expression levels in women diagnosed with breast cancer. Tear samples were collected from 273 participants using Schirmer strip collection methods. Following protein elution, proteome wide trypsin digestion with Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was used to identify potential protein biomarkers with altered expression levels in breast cancer patients. Selected biomarkers were further validated by enzyme linked immunosorbent assay (ELISA). A total of 102 individual tear samples (51 breast cancer, 51 control) were analyzed by LC-MS/MS which identified 301 proteins. Spectral intensities between the groups were compared and 14 significant proteins (p-value <0.05) were identified as potential biomarkers in breast cancer patients. Three biomarkers, S100A8 (p-value = 0.0069, 7.8-fold increase), S100A9 (p-value = 0.0048, 10.2-fold increase), and Galectin-3 binding protein (p-value = 0.01, 3.0-fold increase) with an increased expression in breast cancer patients were selected for validation using ELISA. Validation by ELISA was conducted using 171 individual tear samples (75 Breast Cancer and 96 Control). Similar to the observed LC-MS/MS results, S100A8 (p-value <0.0001) and S100A9 (p-value <0.0001) showed significantly higher expression in breast cancer patients. However, galectin-3 binding protein had increased expression in the control group. Our results provide further support for using tear proteins to detect non-ocular systemic diseases such as breast cancer. Our work provides crucial details to support the continued evaluation of tear samples in the screening and diagnosis of breast cancer and paves the way for future evaluation of the tear proteome for screening and diagnosis of systemic diseases.
AB - The changing expression levels of ocular proteins in response to systemic disease has been well established in literature. In this study, we examined the ocular proteome to identify protein biomarkers with altered expression levels in women diagnosed with breast cancer. Tear samples were collected from 273 participants using Schirmer strip collection methods. Following protein elution, proteome wide trypsin digestion with Liquid chromatography/tandem mass spectrometry (LC-MS/MS) was used to identify potential protein biomarkers with altered expression levels in breast cancer patients. Selected biomarkers were further validated by enzyme linked immunosorbent assay (ELISA). A total of 102 individual tear samples (51 breast cancer, 51 control) were analyzed by LC-MS/MS which identified 301 proteins. Spectral intensities between the groups were compared and 14 significant proteins (p-value <0.05) were identified as potential biomarkers in breast cancer patients. Three biomarkers, S100A8 (p-value = 0.0069, 7.8-fold increase), S100A9 (p-value = 0.0048, 10.2-fold increase), and Galectin-3 binding protein (p-value = 0.01, 3.0-fold increase) with an increased expression in breast cancer patients were selected for validation using ELISA. Validation by ELISA was conducted using 171 individual tear samples (75 Breast Cancer and 96 Control). Similar to the observed LC-MS/MS results, S100A8 (p-value <0.0001) and S100A9 (p-value <0.0001) showed significantly higher expression in breast cancer patients. However, galectin-3 binding protein had increased expression in the control group. Our results provide further support for using tear proteins to detect non-ocular systemic diseases such as breast cancer. Our work provides crucial details to support the continued evaluation of tear samples in the screening and diagnosis of breast cancer and paves the way for future evaluation of the tear proteome for screening and diagnosis of systemic diseases.
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U2 - 10.1371/journal.pone.0267676
DO - 10.1371/journal.pone.0267676
M3 - Article
C2 - 35471994
AN - SCOPUS:85128934341
SN - 1932-6203
VL - 17
JO - PLoS One
JF - PLoS One
IS - 4 April
M1 - e0267676
ER -