title: Quantitative proteomics revealed novel proteins associated with molecular subtypes of breast cancer.
abstract: The early diagnosis and successful treatment of breast cancer (BC) is still a challenging task due to the diverse origin and functional heterogeneity of cancer cells. The heterogeneity of BC may likely to explained by molecular BC subtypes, comprises Luminal-A (LA), Luminal-B (LB), Triple-negative (TN) and HER2-positive (HP), which are governed by a variety of cancer associated pathways. To identify protein signatures in different BC subtypes, we performed isobaric tag for absolute and relative quantitation (iTRAQ) of enriched blood plasma samples of BC subtypes (N=32) and healthy subjects (N=8). After analyses of data, 58 proteins were found to be modulated in BC subtypes from healthy subjects (p<0.05) and among these; Fibronectin (FN1), Alpha-2-macroglobulin (A2M), and Complement component-4-binding protein-alpha (C4BPA) and Complement factor-B (CFB) were selected for validation in BC subtypes and healthy subjects in the independent set of blood plasma (N=100) and tissue samples (N=25). Statistical analysis showed the significant modulation of FN1 and C4BPA in LB, and A2M in TN patients in both plasma as well as tissues comparatively control (p<0.05). Further, FN1 and C4BPA in LB subtype revealed a good diagnostic accuracy in plasma level validation. The receiver operating characteristic (ROC) curve and regression analysis demonstrated that these proteins with associated criterion of expression could act as discriminating signatures among BC subtypes with diagnostic and prognostic relevance.
  
  
  
  The heterogeneity of breast cancer (BC) has gained many challenges for successful management of BC, thus, the delineating proteomic alterations BC subtypes may provide great clinical values in diagnostic, prognostic and therapeutics of BC. The findings from the present quantitative proteomic study have deciphered the altered proteomic patterns and their possible molecular interactions in each BC subtype. The study showed a strong association of FN1, A2M, C4BPA and CFB in molecular subtypes of BC, in which, C4BPA and A2M demonstrated a potent signature in blood plasma and tissue samples of LB and TN subtypes in BC patients, respectively. The findings also revealed the altered level expressions of these selected proteins could classify BC subtypes through plasma and tissue based expression analysis in patients and control samples. Hence, these proteins could have clinical importance for the diagnosis and prognosis purposes among molecular BC subtypes.
authors: Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, Uttar Pradesh, India.
authors: Shankar
authors: S
authors: Suman
authors: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, Uttar Pradesh, India.
authors: Trayambak
authors: T
authors: Basak
authors: Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, Uttar Pradesh, India.
authors: Prachi
authors: P
authors: Gupta
authors: Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, Uttar Pradesh, India.
authors: Sanjay
authors: S
authors: Mishra
authors: Department of Surgical Oncology, King George Medical University, Lucknow, Uttar Pradesh, India.
authors: Vijay
authors: V
authors: Kumar
authors: Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, Uttar Pradesh, India.
authors: Shantanu
authors: S
authors: Sengupta
authors: Proteomics and Environmental Carcinogenesis Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Campus, Lucknow, Uttar Pradesh, India. Electronic address: yshukla@iitr.res.in.
authors: Yogeshwer
authors: Y
authors: Shukla
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000145:classification / Q000175:diagnosis*; D016022:Case-Control Studies; D050716:Complement C4b-Binding Protein / Q000032:analysis; D005260:Female; D005353:Fibronectins / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008562:Membrane Glycoproteins; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases; D064726:Triple Negative Breast Neoplasms; D000511:alpha-Macroglobulins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D050716:Complement C4b-Binding Protein; D005353:Fibronectins; D008562:Membrane Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000511:alpha-Macroglobulins; C578813:A2M protein, human; C055609:C4BPA protein, human; C067625:FN1 protein, human; C504584:LEA-135 protein, human; C086262:LEA-92 protein, human
keywords: Alpha-2-macroglobulin; BC subtypes; Complement component-4-binding protein-alpha; Complement factor-B; Fibronectin; iTRAQ