title: Quantitative tissue proteomic investigation of invasive ductal carcinoma of breast with luminal B HER2 positive and HER2 enriched subtypes towards potential diagnostic and therapeutic biomarkers.
abstract: Worldwide, breast cancer is one of the frequently diagnosed cancers in women with high mortality if not diagnosed at early stage. Although biomarker discoveries through various proteomic approaches have been studied in breast cancer, a limited number of studies have explored the invasive ductal carcinoma with Luminal B HER2 positive (LB) and HER2 enriched (HE) subtypes. The present study employed the complementary quantitative proteomic approaches to find a panel of markers that could discriminate LB and HE subtypes as well as early (ES) and late stages (LS) of these subtypes. A total of 67 and 68 differentially expressed proteins were identified by DIGE for the subtype and stage wise categories, respectively. Multivariate statistical analysis was employed to identify the set of most significant proteins, which could discriminate between these two subtypes and also early and late stages under study. Immunoblotting and MRM based validation in a separate cohort of samples confirmed that panel of biosignatures for LB are APOA1, GELS, HS90B, EF1A1, NHRF1 and PRDX3 and for HE are PRDX1, CATD, CALR, ATPB and CH60. For the diagnosis of early and late stages the potential markers are TPM4, CATD, PRDX3, ANXA3, HSPB1 and CALR, TRFE, GELS, CH60, CAPG, NHRF1, 1433G, GRP78 respectively.
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune 411007, MH, India; B. J. Medical College, Sassoon Hospital, Pune 411001, MH, India.
authors.forename: Namita
authors.initials: N
authors.lastname: Pendharkar
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune 411007, MH, India.
authors.forename: Akshada
authors.initials: A
authors.lastname: Gajbhiye
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune 411007, MH, India.
authors.forename: Khushman
authors.initials: K
authors.lastname: Taunk
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, WB, India.
authors.forename: Sourav
authors.initials: S
authors.lastname: RoyChoudhury
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune 411007, MH, India.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Dhali
authors.affiliation: Wipro GE Healthcare, Mumbai, MH, India.
authors.forename: Shubhendu
authors.initials: S
authors.lastname: Seal
authors.affiliation: Grant Medical Foundation, Ruby Hall Clinic, Pune 411001, MH, India.
authors.forename: Anupama
authors.initials: A
authors.lastname: Mane
authors.affiliation: B. J. Medical College, Sassoon Hospital, Pune 411001, MH, India.
authors.forename: Subodhini
authors.initials: S
authors.lastname: Abhang
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune 411007, MH, India.
authors.forename: Manas K
authors.initials: MK
authors.lastname: Santra
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, WB, India.
authors.forename: Koel
authors.initials: K
authors.lastname: Chaudhury
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune 411007, MH, India. Electronic address: rsrikanth@nccs.res.in.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Rapole
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006801:Humans; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D009363:Neoplasm Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D009363:Neoplasm Proteins; D020543:Proteome; D018719:Erb-b2 Receptor Tyrosine Kinases; C000717247:HSPA5 protein, human; C508053:ERBB2 protein, human
keywords: 2-D DIGE; Breast cancer; HER2 enriched; Luminal B; Quantitative proteomics; iTRAQ