Prognostic panel for urinary bladder cancer
Patent Number: US8293880
Executive Summary:
General Description:
Multiple alterations in major cancer pathways are responsible for urothelial carcinoma progression. The inventors profiled the expression of genes involved in crucial cancer pathways by standardized competitive reverse transcriptase-polymerase chain reaction (StaRT-PCR). The absolute expressions of these biomarkers were measured in relation to a fixed quantity of the housekeeping gene β-actin. The inventors sought to determine if alterations in molecular pathways could supplement TNM staging in order to more accurately predict clinical outcome in patients with urothelial carcinoma (UC). They established that the expression of a few proteins regulating cell division accurately predicts clinical outcome and therapeutic response.
Scientific Progress:
The predictive panel was trimmed to three genes using machine learning algorithms (ref. 1).
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Publications:
Bartsch G Jr, Mitra AP, Mitra SA, Almal AA, Steven KE, Skinner DG, Fry DW, Lenehan PF, Worzel WP, Cote RJ. Use of Artificial Intelligence and Machine Learning Algorithms with Gene Expression Profiling to Predict Recurrent Nonmuscle Invasive Urothelial Carcinoma of the Bladder. J Urol. 2016 Feb;195(2):493-8. doi:10.1016/j.juro.2015.09.090. Epub 2015 Oct 13. PubMed PMID: 26459038.
Mitra AP, Castelao JE, Hawes D, Tsao-Wei DD, Jiang X, Shi SR, Datar RH, Skinner EC, Stein JP, Groshen S, Yu MC, Ross RK, Skinner DG, Cortessis VK, Cote RJ. Combination of molecular alterations and smoking intensity predicts bladder cancer outcome: a report from the Los Angeles Cancer Surveillance Program. Cancer. 2013 Feb 15;119(4):756-65. doi: 10.1002/cncr.27763. Epub 2013 Jan 14. PubMed PMID: 23319010; PubMed Central PMCID: PMC3565093.
Mitra AP, Hansel DE, Cote RJ. Prognostic value of cell-cycle regulation biomarkers in bladder cancer. Semin Oncol. 2012 Oct;39(5):524-33. doi:10.1053/j.seminoncol.2012.08.008. Review. PubMed PMID: 23040249; PubMed Central PMCID: PMC3478886.
Mitra AP, Jordà M, Cote RJ. Pathological possibilities and pitfalls in detecting aggressive bladder cancer. Curr Opin Urol. 2012 Sep;22(5):397-404. doi:10.1097/MOU.0b013e328356ade6. Review. PubMed PMID: 22825461.
Bartsch G, Mitra AP, Cote RJ. Expression profiling for bladder cancer: strategies to uncover prognostic factors. Expert Rev Anticancer Ther. 2010 Dec;10(12):1945-54. doi: 10.1586/era.10.131. Review. PubMed PMID: 21110760; PubMed Central PMCID: PMC3030446.
Mitra AP, Cote RJ. Molecular screening for bladder cancer: progress and potential. Nat Rev Urol. 2010 Jan;7(1):11-20. doi: 10.1038/nrurol.2009.236. Review. PubMed PMID: 20062071.
Mitra AP, Bartsch CC, Cote RJ. Strategies for molecular expression profiling in bladder cancer. Cancer Metastasis Rev. 2009 Dec;28(3-4):317-26. doi:10.1007/s10555-009-9196-5. Review. PubMed PMID: 19997771.
Shariat SF, Chade DC, Karakiewicz PI, Ashfaq R, Isbarn H, Fradet Y, Bastian PJ, Nielsen ME, Capitanio U, Jeldres C, Montorsi F, Lerner SP, Sagalowsky AI, Cote RJ, Lotan Y. Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer. J Urol. 2010 Jan;183(1):68-75. doi: 10.1016/j.juro.2009.08.115. PubMed PMID: 19913255.
Birkhahn M, Mitra AP, Williams AJ, Lam G, Ye W, Datar RH, Balic M, Groshen S, Steven KE, Cote RJ. Predicting recurrence and progression of noninvasive papillary bladder cancer at initial presentation based on quantitative gene expression profiles. Eur Urol. 2010 Jan;57(1):12-20. doi:10.1016/j.eururo.2009.09.013. Epub 2009 Sep 9. PubMed PMID: 19762144; PubMed Central PMCID: PMC2828516.
Mitra AP, Pagliarulo V, Yang D, Waldman FM, Datar RH, Skinner DG, Groshen S, Cote RJ. Generation of a concise gene panel for outcome prediction in urinary bladder cancer. J Clin Oncol. 2009 Aug 20;27(24):3929-37. doi:10.1200/JCO.2008.18.5744. Epub 2009 Jul 20. PubMed PMID: 19620494; PubMed Central PMCID: PMC2799152.
Inventor Bio: Richard J. Cote
https://www.chem.uci.edu/sites/chem.uci.edu/files/Dr.%20Richard%20Cote%20Bio%20.pdf
Executive Summary:
- Invention Type: Prognostic
- Patent Status: US grant, Active
- Patent Link: https://patents.google.com/patent/US8293880/
- Research Institute: University of Southern California
- Disease Focus: Bladder cancer
- Basis of Invention: The inventors quantified expression of 69 genes from urinary carcinoma patients and health individuals. Six and ten genes were significantly associated with time to recurrence and overall survival, respectively. Four genes, expression of which reliably predicts both parameters, were also identified
- How it works: RNA is isolated from the tumor, and the amount of RNA encoding the biomarkers is determined by quantitative standardized reverse transcription – polymerase chain reaction. The treatment strategy and the potential clinical outcome are predicted based on the expression level of the biomarkers
- Lead Challenge Inventor: Richard J. Cote
- Inventors: Richard J. Cote, Anirban P. Mitra
- Development Stage: Validated on patient samples from an independent cohort
- Novelty:
- Use of a limited amount of pre-determined biomarkers instead of microarrays
- Use of a reproducible polymerase chain reaction protocol instead of microarrays
- Clinical Applications:
- Prognosis of urinary carcinoma outcome
- Determination of the treatment strategy
General Description:
Multiple alterations in major cancer pathways are responsible for urothelial carcinoma progression. The inventors profiled the expression of genes involved in crucial cancer pathways by standardized competitive reverse transcriptase-polymerase chain reaction (StaRT-PCR). The absolute expressions of these biomarkers were measured in relation to a fixed quantity of the housekeeping gene β-actin. The inventors sought to determine if alterations in molecular pathways could supplement TNM staging in order to more accurately predict clinical outcome in patients with urothelial carcinoma (UC). They established that the expression of a few proteins regulating cell division accurately predicts clinical outcome and therapeutic response.
Scientific Progress:
The predictive panel was trimmed to three genes using machine learning algorithms (ref. 1).
Future Directions:
- Additional independent validation
- Introduction into the clinical practice
Strengths:
- Robust validation on independent cohort of patients
Weaknesses:
- The technology is limited to a single type of cancer
Patent Status:
- Filing date: 2009-03-25
- Publication date and Grant date: 2012-10-23
- Other version: US20090246790A1 (Application)
Publications:
Bartsch G Jr, Mitra AP, Mitra SA, Almal AA, Steven KE, Skinner DG, Fry DW, Lenehan PF, Worzel WP, Cote RJ. Use of Artificial Intelligence and Machine Learning Algorithms with Gene Expression Profiling to Predict Recurrent Nonmuscle Invasive Urothelial Carcinoma of the Bladder. J Urol. 2016 Feb;195(2):493-8. doi:10.1016/j.juro.2015.09.090. Epub 2015 Oct 13. PubMed PMID: 26459038.
Mitra AP, Castelao JE, Hawes D, Tsao-Wei DD, Jiang X, Shi SR, Datar RH, Skinner EC, Stein JP, Groshen S, Yu MC, Ross RK, Skinner DG, Cortessis VK, Cote RJ. Combination of molecular alterations and smoking intensity predicts bladder cancer outcome: a report from the Los Angeles Cancer Surveillance Program. Cancer. 2013 Feb 15;119(4):756-65. doi: 10.1002/cncr.27763. Epub 2013 Jan 14. PubMed PMID: 23319010; PubMed Central PMCID: PMC3565093.
Mitra AP, Hansel DE, Cote RJ. Prognostic value of cell-cycle regulation biomarkers in bladder cancer. Semin Oncol. 2012 Oct;39(5):524-33. doi:10.1053/j.seminoncol.2012.08.008. Review. PubMed PMID: 23040249; PubMed Central PMCID: PMC3478886.
Mitra AP, Jordà M, Cote RJ. Pathological possibilities and pitfalls in detecting aggressive bladder cancer. Curr Opin Urol. 2012 Sep;22(5):397-404. doi:10.1097/MOU.0b013e328356ade6. Review. PubMed PMID: 22825461.
Bartsch G, Mitra AP, Cote RJ. Expression profiling for bladder cancer: strategies to uncover prognostic factors. Expert Rev Anticancer Ther. 2010 Dec;10(12):1945-54. doi: 10.1586/era.10.131. Review. PubMed PMID: 21110760; PubMed Central PMCID: PMC3030446.
Mitra AP, Cote RJ. Molecular screening for bladder cancer: progress and potential. Nat Rev Urol. 2010 Jan;7(1):11-20. doi: 10.1038/nrurol.2009.236. Review. PubMed PMID: 20062071.
Mitra AP, Bartsch CC, Cote RJ. Strategies for molecular expression profiling in bladder cancer. Cancer Metastasis Rev. 2009 Dec;28(3-4):317-26. doi:10.1007/s10555-009-9196-5. Review. PubMed PMID: 19997771.
Shariat SF, Chade DC, Karakiewicz PI, Ashfaq R, Isbarn H, Fradet Y, Bastian PJ, Nielsen ME, Capitanio U, Jeldres C, Montorsi F, Lerner SP, Sagalowsky AI, Cote RJ, Lotan Y. Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer. J Urol. 2010 Jan;183(1):68-75. doi: 10.1016/j.juro.2009.08.115. PubMed PMID: 19913255.
Birkhahn M, Mitra AP, Williams AJ, Lam G, Ye W, Datar RH, Balic M, Groshen S, Steven KE, Cote RJ. Predicting recurrence and progression of noninvasive papillary bladder cancer at initial presentation based on quantitative gene expression profiles. Eur Urol. 2010 Jan;57(1):12-20. doi:10.1016/j.eururo.2009.09.013. Epub 2009 Sep 9. PubMed PMID: 19762144; PubMed Central PMCID: PMC2828516.
Mitra AP, Pagliarulo V, Yang D, Waldman FM, Datar RH, Skinner DG, Groshen S, Cote RJ. Generation of a concise gene panel for outcome prediction in urinary bladder cancer. J Clin Oncol. 2009 Aug 20;27(24):3929-37. doi:10.1200/JCO.2008.18.5744. Epub 2009 Jul 20. PubMed PMID: 19620494; PubMed Central PMCID: PMC2799152.
Inventor Bio: Richard J. Cote
https://www.chem.uci.edu/sites/chem.uci.edu/files/Dr.%20Richard%20Cote%20Bio%20.pdf
