Krüppel-Like Factor 4 and Colon Cancer Open Access

Abstract

Krüppel-Like Factor 4 and Colon Cancer
By Nilesh Patel
Purpose : The zinc finger transcription factor Krüppel-Like Factor 4 (KLF4) has critical
roles in both normal intestinal development and intestinal carcinogenesis. Various studies
have investigated its role in wnt signaling, cell cycle progression, apoptosis, and cell to
cell adhesion. To further elucidate its role, we have correlated the expression pattern of
KLF4 with various clinical outcomes.
Experimental Design : We employed a tissue microarray consisting of 367 independent
colon cancer sections to investigate KLF4 in human tissues. Univariate KLF4 data
analysis was performed in addition to construction of multivariate models with several
clinicopathologic factors to evaluate KLF4 as an independent predictor of survival and
cancer recurrence.
Results : Cancer tissues had significantly less KLF4 expression overall in comparison to
non-cancer tissues (p<0.0001). Using logistic regression, a trend, though not significant,
was noted such that higher stages of cancer had decreased odds of KLF4 expression. In
univariate survival and recurrent analysis, KLF4 was a significant predictor of survival
and recurrence. This relationship, was not, however, independent of other covariates.
Conclusions : KLF4 expression is significantly down-regulated in intestinal tumors, but
loss of KLF4 is not an independent predictor of survival or recurrence.

Table of Contents

TABLE OF CONTENTS

Introduction ………………………………………………………..................... 1

Background ………………………………………………………..................... 3
Methods
………………………………………………………..................... 8
Results
………………………………………………………..................... 12
Discussion
………………………………………………………..................... 15
Tables and Figures
………………………………………………….................. 18
Table 1a: Characteristics of participants………………………………………………….. 18
Table 1b: General characteristics of tumors included in the tissue microarray…............... 19
Table 2a: Univariate measures of covariates among cancer patients………….................. 20
Table 2b: Univariate measures of covariates among stage I cancer patients……….......... 20
Table 2c: Univariate measures of covariates among stage II cancer patients……………. 21
Table 2d: Univariate measures of covariates among stage III cancer patients…............... 21
Table 2e: Univariate measures of covariates among stage IV cancer patients……........... 22
Table 2f: Assessment of interaction of covariates in determining the odds ratio for KLF4
given age (>70/<70)………………………………...………………................... 23
Table 2g: Assessment of interaction of covariates in determining the odds ratio for KLF4
given race (white/non-white)…………………………………………………..... 23
Table 2h: Assessment of interaction of covariates in determining the odds ratio for KLF4
given gender (male/female)……………………………………………………… 23
Table 3a: Multivariate analysis of KLF4 using a binary logistic model including all
available covariates...……………………………………………………....……. 24
Table 3b: Multivariate analysis of KLF4 using a binary logistic model including all
possible two way interaction terms. ...………………………………………….. 25
Figure 1: Representative samples of KLF4 staining………………………….................... 26
Figure 2: Overall Kaplan-Meier survival curve with all patients…………….................... 27
Figure 3a: Kaplan-Meier survival curve among stage I patients.………………………… 28
Figure 3b: Kaplan-Meier survival curve among stage II patients………………………… 29
Figure 3c: Kaplan-Meier survival curve among stage III patients……………….............. 30
Figure 3d: Kaplan-Meier survival curve among stage IV patients……………………….. 31
Figure 4: Overall Kaplan-Meier disease-free survival curve with all patients…………… 32

Figure 5a: Kaplan-Meier diseases free-survival curve among stage I patients…………… 33
Figure 5b: Kaplan-Meier diseases free-survival curve among stage II patients………….. 34
Figure 5c: Kaplan-Meier diseases free-survival curve among stage III patients…………. 35
Table 4a: Cox proportional hazards model for overall survival, without adjustment…..... 36
Table 4b: Final extended Cox model for overall survival stratified by stage…………….. 36
Table 5a: Cox proportional hazards model for disease free-survival, without
adjustment……………………………………………………………………….. 37
Table 5b: Final extended Cox model for disease free-survival……………...……………. 37
References
………………………………………………………..................... 38

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research Curriculum Program
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery
Keyword	Microarray Kruppel-Like KLF4 Colon Cancer
Committee Chair / Thesis Advisor	Yang, Vincent W, Emory University
Committee Members	Boring, John R, Emory University McGowan Jr., John E, Emory University Ziegler, Thomas R, Emory University

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