Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis

Manisha Bajpai, Darren Seril, James Van Gurp, Xin Geng, Janet Alvarez, Carlos D. Minacapelli, Steve Gorin, Koushik K. Das, Elizabeth Poplin, Jerry Cheng, Peter S. Amenta, Kiron M. Das

Research output: Contribution to journalArticle

Abstract

Background: The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. Aim: This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. Methods: Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2–6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. Results: The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005–0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. Conclusion: This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.

Original languageEnglish (US)
Pages (from-to)740-750
Number of pages11
JournalDigestive diseases and sciences
Volume64
Issue number3
DOIs
StatePublished - Mar 15 2019

Fingerprint

Mesalamine
Neoplasm Genes
Ulcerative Colitis
Mucous Membrane
Gene Expression
Interleukin-8
Linear Models
Colon
NF-kappa B
Endoscopy
Carcinogenesis
Biopsy
Therapeutics
Peroxisome Proliferator-Activated Receptors
Colonoscopy
Observational Studies
Colorectal Neoplasms
Regression Analysis
Maintenance
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

Keywords

  • 5-aminosalicylic acid (5-ASA)
  • Chemoprevention
  • Ulcerative colitis (UC)

Cite this

Bajpai, Manisha ; Seril, Darren ; Van Gurp, James ; Geng, Xin ; Alvarez, Janet ; Minacapelli, Carlos D. ; Gorin, Steve ; Das, Koushik K. ; Poplin, Elizabeth ; Cheng, Jerry ; Amenta, Peter S. ; Das, Kiron M. / Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis. In: Digestive diseases and sciences. 2019 ; Vol. 64, No. 3. pp. 740-750.
@article{e2460c6362bc4fdfbd076473265c289b,
title = "Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis",
abstract = "Background: The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. Aim: This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. Methods: Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2–6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. Results: The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005–0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. Conclusion: This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.",
keywords = "5-aminosalicylic acid (5-ASA), Chemoprevention, Ulcerative colitis (UC)",
author = "Manisha Bajpai and Darren Seril and {Van Gurp}, James and Xin Geng and Janet Alvarez and Minacapelli, {Carlos D.} and Steve Gorin and Das, {Koushik K.} and Elizabeth Poplin and Jerry Cheng and Amenta, {Peter S.} and Das, {Kiron M.}",
year = "2019",
month = "3",
day = "15",
doi = "10.1007/s10620-018-5378-8",
language = "English (US)",
volume = "64",
pages = "740--750",
journal = "American Journal of Digestive Diseases",
issn = "0002-9211",
publisher = "Springer New York",
number = "3",

}

Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis. / Bajpai, Manisha; Seril, Darren; Van Gurp, James; Geng, Xin; Alvarez, Janet; Minacapelli, Carlos D.; Gorin, Steve; Das, Koushik K.; Poplin, Elizabeth; Cheng, Jerry; Amenta, Peter S.; Das, Kiron M.

In: Digestive diseases and sciences, Vol. 64, No. 3, 15.03.2019, p. 740-750.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis

AU - Bajpai, Manisha

AU - Seril, Darren

AU - Van Gurp, James

AU - Geng, Xin

AU - Alvarez, Janet

AU - Minacapelli, Carlos D.

AU - Gorin, Steve

AU - Das, Koushik K.

AU - Poplin, Elizabeth

AU - Cheng, Jerry

AU - Amenta, Peter S.

AU - Das, Kiron M.

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Background: The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. Aim: This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. Methods: Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2–6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. Results: The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005–0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. Conclusion: This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.

AB - Background: The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. Aim: This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. Methods: Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2–6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. Results: The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005–0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. Conclusion: This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.

KW - 5-aminosalicylic acid (5-ASA)

KW - Chemoprevention

KW - Ulcerative colitis (UC)

UR - http://www.scopus.com/inward/record.url?scp=85057339487&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057339487&partnerID=8YFLogxK

U2 - 10.1007/s10620-018-5378-8

DO - 10.1007/s10620-018-5378-8

M3 - Article

C2 - 30478770

AN - SCOPUS:85057339487

VL - 64

SP - 740

EP - 750

JO - American Journal of Digestive Diseases

JF - American Journal of Digestive Diseases

SN - 0002-9211

IS - 3

ER -