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PREDICTING BLADDER CANCER BEHAVIOR BY MOLECULAR
EXPRESSION PROFILING
by
Anirban Pradip Mitra
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PATHOBIOLOGY)
August 2009
Copyright 2009 Anirban Pradip Mitra
Object Description
| Title | Predicting bladder cancer behavior by molecular expression profiling |
| Author | Mitra, Anirban Pradip |
| Author email | amitra@usc.edu; apmitra123@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Pathobiology |
| School | Keck School of Medicine |
| Date defended/completed | 2009-05-11 |
| Date submitted | 2009 |
| Restricted until | Unrestricted |
| Date published | 2009-06-14 |
| Advisor (committee chair) |
Cote, Richard J. Taylor, Clive R. |
| Advisor (committee member) |
Triche, Timothy J. Groshen, Susan |
| Abstract | Urothelial carcinoma of the urinary bladder is the seventh most common type of cancer worldwide. In the western world, cigarette smoke is the most commonly implicated carcinogen for this disease. Bladder cancer presents itself as two prognostic variants -- the more common noninvasive Ta tumors that frequently recur but rarely invade the basement membrane, and the less common invasive tumors that tend to progress and metastasize. Traditional prognostic metrics, including tumor and nodal stage, are currently the best clinical predictors of subsequent behavior.; While lymph node metastasis forebodes a poor prognosis, early detection can allow for radical lymphadenectomy with a curative intent. This manuscript begins by describing a study that used gene expression profiles generated from primary bladder tumors to construct signatures that could identify nodal metastasis. Genetic programming was used to identify classifiers that showed a strong predilection for ICAM1, MAP2K6 and KDR, and could detect nodal metastasis with reasonable sensitivity and specificity. Using similar pathway-based profiling approaches, this manuscript further describes studies that sought to determine if such molecular alterations could supplement traditional pathologic staging to better predict clinical outcome. The manuscript documents the identification and validation of a concise, biologically relevant gene panel comprising of JUN, MAP2K6, STAT3, and ICAM1 that could predict recurrence and survival in bladder cancer. Another study highlights attempts to identify genes profiled from primary noninvasive Ta tumors at first presentation that could predict local recurrence and tumor progression. The final study describes efforts to semi-quantitatively profile expressions of select proteins from primary bladder cancer tissues to analyze associations of their alterations with cigarette smoking, nonsteroidal anti-inflammatory drug use, and clinical outcome across all disease stages in a population-based cohort.; These studies underscore the concept that a pathway-specific approach to profiling relevant biomolecules in bladder cancer can identify markers of prognostic significance, and patients who will recur and/or progress despite definitive surgery alone. Such identification of specific molecular alterations in individual tumors will allow for a more accurate and personalized prediction of prognosis, and also identify potential therapeutic targets. |
| Keyword | urothelial carcinoma; prognosis; quantitative expression profiling; genetic programming; microarray; immunohistochemistry |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2293 |
| Rights | Mitra, Anirban Pradip |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Mitra-2943 |
| Archival file | uscthesesreloadpub_Volume44/etd-Mitra-2943.pdf |
Description
| Title | Page 1 |
| Full text | PREDICTING BLADDER CANCER BEHAVIOR BY MOLECULAR EXPRESSION PROFILING by Anirban Pradip Mitra A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PATHOBIOLOGY) August 2009 Copyright 2009 Anirban Pradip Mitra |
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