Prachi Gupta1,2, Shankar Suman1,2, Manisha Mishra3,2, Sanjay Mishra1,2, Nidhi Srivastava4,2, Vijay Kumar5, Pradhyumna Kumar Singh3, Yogeshwer Shukla1. 1. Proteomics and Environment Carcinogenesis Laboratory, Food, Drug and Chemical Toxicology, Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India. 2. Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, Uttar Pradesh, India. 3. Plant Molecular Biology Laboratory, CSIR-National Botanical Research Institute, Lucknow, Uttar Pradesh, India. 4. Environment Toxicology Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India. 5. Department of Surgical Oncology, King George's Medical University, Lucknow, Uttar Pradesh, India.
Abstract
PURPOSE: Breast cancer (BC) is the most common invasive cancer in women worldwide. Autoantibodies (AAbs) to tumor-associated antigens (TAAs) have a great potential for the development of diagnostic biomarkers in cancer. This study was performed to identify AAbs and cognate TAAs that may improve detection of this deadly disease. EXPERIMENTAL DESIGN: Serological proteome analysis of plasma samples of BC patients (N = 30) and healthy controls (N = 30) was performed to identify TAAs. Expressions of selected TAAs were also determined in breast tumor tissues (N = 10) by immunohistochemistry. An independent validation cohort (N = 124) was tested to determine diagnostic accuracy of selected AAbs titer by ELISA. RESULTS: Thymidylate synthase (TYMS) and C-terminal LIM domain protein 1 (PDLIM1) were found to react more specifically with plasma samples of BC patients. Both TAAs were also found to be significantly over expressed (p < 0.001) in breast tumor tissues compared to adjacent normal tissues. TYMS AAbs response was positively correlated (r = 0.778, p < 0.008) with TYMS overexpression in BC tissues. TYMS and PDLIM1 AAbs titers discriminated BC from controls with a sensitivity/specificity of 57.81%/95% and 73.44%/58.33%, respectively. CONCLUSION AND CLINICAL RELEVANCE: High titers of both TYMS and PDLIM1 AAbs were significantly more prevalent in BC cases than controls. Our data recommends further investigations for evaluating their potential for BC detection.
PURPOSE:Breast cancer (BC) is the most common invasive cancer in women worldwide. Autoantibodies (AAbs) to tumor-associated antigens (TAAs) have a great potential for the development of diagnostic biomarkers in cancer. This study was performed to identify AAbs and cognate TAAs that may improve detection of this deadly disease. EXPERIMENTAL DESIGN: Serological proteome analysis of plasma samples of BC patients (N = 30) and healthy controls (N = 30) was performed to identify TAAs. Expressions of selected TAAs were also determined in breast tumor tissues (N = 10) by immunohistochemistry. An independent validation cohort (N = 124) was tested to determine diagnostic accuracy of selected AAbs titer by ELISA. RESULTS:Thymidylate synthase (TYMS) and C-terminal LIM domain protein 1 (PDLIM1) were found to react more specifically with plasma samples of BC patients. Both TAAs were also found to be significantly over expressed (p < 0.001) in breast tumor tissues compared to adjacent normal tissues. TYMS AAbs response was positively correlated (r = 0.778, p < 0.008) with TYMS overexpression in BC tissues. TYMS and PDLIM1 AAbs titers discriminated BC from controls with a sensitivity/specificity of 57.81%/95% and 73.44%/58.33%, respectively. CONCLUSION AND CLINICAL RELEVANCE: High titers of both TYMS and PDLIM1 AAbs were significantly more prevalent in BC cases than controls. Our data recommends further investigations for evaluating their potential for BC detection.