title: Investigation of serum proteome alterations in human endometriosis.
abstract: Endometriosis is a common benign gynecological disease, characterized by proliferation of functional endometrial glands and stroma outside the uterine cavity. The present study involves investigation of alterations in the serum proteome of endometriosis patients compared to healthy controls using 2DE and 2D-DIGE combined with MALDI TOF/TOF-MS. Comparison of serum proteome of endometriosis patients and healthy subjects revealed 25 significant differentially expressed proteins. Gene ontology and network analysis, performed using PANTHER, DAVID, WebGestalt and STRING, revealed that the differentially expressed proteins are majorly involved in response to stimulus, immune system, metabolic, localization and cellular processes. For serum diagnostic marker identification, several robust statistical screening procedures were applied to identify the set of the most significant proteins responsible for successful diagnosis of different endometriosis stages. Partial least squares (PLS) based marker selection tool and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to identify the most significant proteins for disease prediction. Western blotting validation in a separate cohort of patients revealed that haptoglobin (HP), Ig kappa chain C region (IGKC), alpha-1B-glycoprotein (A1BG) can be considered effective serum protein markers for the diagnosis of Stage II, III and IV endometriosis. For diagnosis of Stage I, only IGKC and HP seemed promising.
  
  
  CONCLUSIONS
  Globally, about 12 in 100 women of reproductive age are diagnosed with endometriosis. The pathogenesis of the disease still remains unclear, leading to non-specific therapeutic approaches for disease management. Moreover, there is a delay of 8-12years in correct diagnosis after the initial onset of symptoms leading to a considerable impact on the woman's lifestyle. Also, the gold standard for diagnosis of endometriosis, laparoscopy, is an invasive procedure. The value of a noninvasive or semi-invasive diagnostic test for endometriosis with easily accessible fluids such as plasma, serum, urine, and saliva is, therefore, rightfully recognized. The present study is expected to considerably improve the understanding of the disease pathogenesis along with improved diagnostics and therapeutic approaches leading to better management of the disease.
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India.
authors.forename: Mainak
authors.initials: M
authors.lastname: Dutta
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India.
authors.forename: Elavarasan
authors.initials: E
authors.lastname: Subramani
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, India.
authors.forename: Khushman
authors.initials: K
authors.lastname: Taunk
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, India.
authors.forename: Akshada
authors.initials: A
authors.lastname: Gajbhiye
authors.affiliation: Wipro GE Healthcare, Mumbai, India.
authors.forename: Shubhendu
authors.initials: S
authors.lastname: Seal
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, India.
authors.forename: Namita
authors.initials: N
authors.lastname: Pendharkar
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, India.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Dhali
authors.affiliation: Institute of Post Graduate Medical Education & Research, Obstetrics & Gynecology, Kolkata, West Bengal, India.
authors.forename: Chaitali Datta
authors.initials: CD
authors.lastname: Ray
authors.affiliation: Institute of Reproductive Medicine, Sector-III, Kolkata, West Bengal, India.
authors.forename: Indrani
authors.initials: I
authors.lastname: Lodh
authors.affiliation: Institute of Reproductive Medicine, Sector-III, Kolkata, West Bengal, India.
authors.forename: Baidyanath
authors.initials: B
authors.lastname: Chakravarty
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Kharagpur, West Bengal, India.
authors.forename: Swagata
authors.initials: S
authors.lastname: Dasgupta
authors.affiliation: Proteomics Lab, National Centre for Cell Science, Ganeshkhind, Pune, Maharashtra, India.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Rapole
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, India. Electronic address: koel@smst.iitkgp.ernet.in.
authors.forename: Koel
authors.initials: K
authors.lastname: Chaudhury
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism*; D016022:Case-Control Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D004715:Endometriosis / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020543:Proteome
keywords: 2D-DIGE; Endometriosis; Pathogenesis; Protein markers; Serum