REG4 independently predicts better prognosis in non-mucinous colorectal cancer.

INTRODUCTION:Colorectal cancer (CRC) is one of the world's three most common cancers and its incidence is rising. To identify patients who benefit from adjuvant therapy requires novel biomarkers. The regenerating islet-derived gene (REG) 4 belongs to a group of small secretory proteins involved...

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Main Authors: Tuomas Kaprio, Jaana Hagström, Harri Mustonen, Selja Koskensalo, Leif C Andersson, Caj Haglund
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4190354?pdf=render
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author Tuomas Kaprio
Jaana Hagström
Harri Mustonen
Selja Koskensalo
Leif C Andersson
Caj Haglund
author_facet Tuomas Kaprio
Jaana Hagström
Harri Mustonen
Selja Koskensalo
Leif C Andersson
Caj Haglund
author_sort Tuomas Kaprio
collection DOAJ
description INTRODUCTION:Colorectal cancer (CRC) is one of the world's three most common cancers and its incidence is rising. To identify patients who benefit from adjuvant therapy requires novel biomarkers. The regenerating islet-derived gene (REG) 4 belongs to a group of small secretory proteins involved in cell proliferation and regeneration. Its up-regulated expression occurs in inflammatory bowel diseases also in gastrointestinal cancers. Reports on the association of REG4 expression with CRC prognosis have been mixed. Our aim was to investigate tumor REG4 expression in CRC patients and its coexpression with other intestinal markers. METHODS:Tumor expression of REG4 was evaluated by immunohistochemistry in 840 consecutive surgically treated CRC patients at Helsinki University Central Hospital. Expression of MUC1, MUC2, MUC5AC, synapthophysin, and chromogranin was evaluated in a subgroup of 220 consecutively operated CRC patients. REG4 expression with clinicopathological parameters, other intestinal markers, and the impact of REG4 expression on survival were assessed. RESULTS:REG4 expression associated with favorable clinicopathological parameters and with higher overall survival from non-mucinous CRC (p = 0.019). For such patients under 65, its expression was an independent marker of lower risk of death within 5 years that cancer; univariable hazard ratio (HR) = 0.57; 95% confidence interval (CI) (0.34-0.94); multivariable HR = 0.55; 95% CI (0.33-0.92). In non-mucinous CRC, REG4 associated with positive MUC2, MUC4, and MUC5AC expression. CONCLUSION:We show, to our knowledge for the first time, that REG4 IHC expression to be an independent marker of favorable prognosis in non-mucinous CRC. Our results contradict those from studies based on quantification of REG4 mRNA levels, a discrepancy warranting further studies.
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spelling doaj.art-06bab7849c164e0585b618fa23c999552022-12-21T23:00:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e10960010.1371/journal.pone.0109600REG4 independently predicts better prognosis in non-mucinous colorectal cancer.Tuomas KaprioJaana HagströmHarri MustonenSelja KoskensaloLeif C AnderssonCaj HaglundINTRODUCTION:Colorectal cancer (CRC) is one of the world's three most common cancers and its incidence is rising. To identify patients who benefit from adjuvant therapy requires novel biomarkers. The regenerating islet-derived gene (REG) 4 belongs to a group of small secretory proteins involved in cell proliferation and regeneration. Its up-regulated expression occurs in inflammatory bowel diseases also in gastrointestinal cancers. Reports on the association of REG4 expression with CRC prognosis have been mixed. Our aim was to investigate tumor REG4 expression in CRC patients and its coexpression with other intestinal markers. METHODS:Tumor expression of REG4 was evaluated by immunohistochemistry in 840 consecutive surgically treated CRC patients at Helsinki University Central Hospital. Expression of MUC1, MUC2, MUC5AC, synapthophysin, and chromogranin was evaluated in a subgroup of 220 consecutively operated CRC patients. REG4 expression with clinicopathological parameters, other intestinal markers, and the impact of REG4 expression on survival were assessed. RESULTS:REG4 expression associated with favorable clinicopathological parameters and with higher overall survival from non-mucinous CRC (p = 0.019). For such patients under 65, its expression was an independent marker of lower risk of death within 5 years that cancer; univariable hazard ratio (HR) = 0.57; 95% confidence interval (CI) (0.34-0.94); multivariable HR = 0.55; 95% CI (0.33-0.92). In non-mucinous CRC, REG4 associated with positive MUC2, MUC4, and MUC5AC expression. CONCLUSION:We show, to our knowledge for the first time, that REG4 IHC expression to be an independent marker of favorable prognosis in non-mucinous CRC. Our results contradict those from studies based on quantification of REG4 mRNA levels, a discrepancy warranting further studies.http://europepmc.org/articles/PMC4190354?pdf=render
spellingShingle Tuomas Kaprio
Jaana Hagström
Harri Mustonen
Selja Koskensalo
Leif C Andersson
Caj Haglund
REG4 independently predicts better prognosis in non-mucinous colorectal cancer.
PLoS ONE
title REG4 independently predicts better prognosis in non-mucinous colorectal cancer.
title_full REG4 independently predicts better prognosis in non-mucinous colorectal cancer.
title_fullStr REG4 independently predicts better prognosis in non-mucinous colorectal cancer.
title_full_unstemmed REG4 independently predicts better prognosis in non-mucinous colorectal cancer.
title_short REG4 independently predicts better prognosis in non-mucinous colorectal cancer.
title_sort reg4 independently predicts better prognosis in non mucinous colorectal cancer
url http://europepmc.org/articles/PMC4190354?pdf=render
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