Expression of CD147, BIGH3 and Stathmin and their potential role as diagnostic marker in patients with urothelial carcinoma of the bladder

Divya Bhagirath, Nitin Abrol, Rehan Khan, Manoj Sharma, Amlesh Seth, Alpana Sharma

Research output: Contribution to journalArticle

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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1641-1646
Number of pages6
JournalClinica Chimica Acta
Volume413
Issue number19-20
DOIs
StatePublished - Oct 9 2012
Externally publishedYes

Fingerprint

Stathmin
Transitional Cell Carcinoma
Urinary Bladder
Tumors
Carcinoma
Molecules
Urine
Extracellular Matrix Proteins
Serum
Neoplasms
ROC Curve
Cells
Messenger RNA
Microtubule Proteins
Sensitivity and Specificity
Urothelium
Cystoscopy
Prostatic Hyperplasia
Muscle
Proteins

Keywords

  • BIGH3
  • Bladder cancer
  • CD147
  • Diagnostic marker
  • Stathmin

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Expression of CD147, BIGH3 and Stathmin and their potential role as diagnostic marker in patients with urothelial carcinoma of the bladder. / Bhagirath, Divya; Abrol, Nitin; Khan, Rehan; Sharma, Manoj; Seth, Amlesh; Sharma, Alpana.

In: Clinica Chimica Acta, Vol. 413, No. 19-20, 09.10.2012, p. 1641-1646.

Research output: Contribution to journalArticle

Bhagirath, Divya ; Abrol, Nitin ; Khan, Rehan ; Sharma, Manoj ; Seth, Amlesh ; Sharma, Alpana. / Expression of CD147, BIGH3 and Stathmin and their potential role as diagnostic marker in patients with urothelial carcinoma of the bladder. In: Clinica Chimica Acta. 2012 ; Vol. 413, No. 19-20. pp. 1641-1646.
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AU - Sharma, Manoj

AU - Seth, Amlesh

AU - Sharma, Alpana

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AB - 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. Conclusion: 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.

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