title: Expression of CD147, BIGH3 and Stathmin and their potential role as diagnostic marker in patients with urothelial carcinoma of the bladder.
abstract: BACKGROUND
  Urothelial carcinoma of the bladder is characterised by very high recurrence rate, followed up by cystoscopy which being invasive technique makes the need for non-invasive markers important for Transitional Cell Carcinoma (TCC) detection. CD147 is a transmembrane protein highly expressed in tumour cells which aids in tumour invasion and growth. BIGH3, an Extracellular matrix protein (ECM) which interacts with various ECM component in different tissue system and Stathmin(STMN1) is cytosolic microtubule destabilising protein also called as Oncoprotein18 due to its role in tumour promotion. So far the expression of BIGH3 and STMN1 remains undetermined in cancer subjects including TCC. We therefore studied the levels and molecular expression of these molecules in TCC patients, to evaluate their usefulness as diagnostic markers.
  
  
  METHODS
  Thirty consecutive TCC patients and two sets of control- 15 Benign prostatic hyperplasia (BPH) patient and 15 healthy were taken. Serum and urine levels of these molecules were estimated by ELISA and relative mRNA expression by Q-PCR from tumour and normal urothelium. Post-Hoc analysis and ROC curve were determined to evaluate the significance and sensitivity and specificity.
  
  
  RESULTS
  The mean concentrations of these molecules were found to be significantly increased (p<0.001) in the serum and urine of TCC patients, with varying significance in each grade for different molecules. The urinary levels of CD147 (67 pg/ml) and serum STMN1 concentration (1.38 ng/ml) showed a specific increase as compared to the controls, while BIGH3 was elevated in both serum and urine samples. Molecular (mRNA) expression was elevated in the high grade (Muscle Invasive) stage of the disease for all the molecules, with a significant 3-fold increase that correlated with disease severity being observed for STMN1. ROC analysis gave optimal combination of sensitivity and specificity for diagnosis of the disease in urine and serum sample for STMN1.
  
  
  CONCLUSIONS
  Of CD147, BIGH3 and STMN1, significant results were obtained for STMN1 and it could serve as the best possible diagnostic marker for TCC detection in future.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences-AIIMS, New Delhi, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Bhagirath
authors.forename: Nitin
authors.initials: N
authors.lastname: Abrol
authors.forename: Rehan
authors.initials: R
authors.lastname: Khan
authors.forename: Manoj
authors.initials: M
authors.lastname: Sharma
authors.forename: Amlesh
authors.initials: A
authors.lastname: Seth
authors.forename: Alpana
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000368:Aged; D051926:Basigin / Q000097:blood / Q000235:genetics* / Q000652:urine; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics* / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000235:genetics* / Q000652:urine; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012333:RNA, Messenger / Q000096:biosynthesis; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D050777:Stathmin / Q000097:blood / Q000235:genetics* / Q000652:urine; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics* / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000652:urine; D000099222:betaIG-H3 Protein
chemical_list: D051926:Basigin; D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D050777:Stathmin; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C497886:BSG protein, human; C493995:STMN1 protein, human