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 N.
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.
N1 - Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.
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
U2 - 10.1007/s10620-018-5378-8
DO - 10.1007/s10620-018-5378-8
M3 - Article
C2 - 30478770
AN - SCOPUS:85057339487
SN - 0163-2116
VL - 64
SP - 740
EP - 750
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 3
ER -