High immunoreactivity of duox2 is associated with poor response to preoperative chemoradiation therapy and worse prognosis in rectal cancers

Shih Chun Lin, I. Wei Chang, Pei Ling Hsieh, Ching Yih Lin, Ding Ping Sun, Ming Jen Sheu, Ching Chieh Yang, Li Ching Lin, Hong Lin He, Yu Feng Tian

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Purpose: Colorectal cancer is the third most common cancer and also the fourth most common cause of cancer mortality worldwide. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that DUOX2 was the most significantly up-regulated transcript among those related to cytokine and chemokine mediated signaling pathway (GO:0019221). Hence, the aim of this study was to assess the DUOX2 expression level and its clinicopathological correlation and prognostic significance in patients of rectal cancer. Materials and Methods: DUOX2 immunostain was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by radical proctectomy, which were divided into high- and low-expression subgroups. Furthermore, statistical analyses were examined to correlate the relationship between DUOX2 immunoreactivity and important clinical and pathological characteristics, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: DUOX2 overexpression was linked to post-CCRT tumor advancement, pre- and post-CCRT nodal metastasis and poor response to CCRT (all P ≤ 0.021). Furthermore, DUOX2 high expression was significantly associated with inferior DSS, LRFS and MeFS in univariate analysis (P ≤ 0.0097) and also served as an independent prognosticator indicating shorter DSS and LRFS interval in multivariate analysis (hazard ratio (HR) = 3.413, 95% confidence interval (CI): 1.349-8.633; HR = 4.533, 95% CI: 1.499-13.708, respectively). Conclusion: DUOX2 may play a pivotal role in carcinogenesis, tumor progression and response to neoadjuvant CCRT in rectal cancers, and serve as a novel prognostic biomarker. Additional researches to clarify the molecular and biochemical pathways are essential for developing promising DUOX2-targeted therapies for patients with rectal cancers.

Original languageEnglish
Article number19545
JournalJournal of Cancer
Volume8
Issue number14
DOIs
Publication statusPublished - Jan 1 2017
Externally publishedYes

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Rectal Neoplasms
Chemoradiotherapy
Survival
Therapeutics
Neoplasm Metastasis
Recurrence
Neoplasms
Confidence Intervals
Information Centers
Data Mining
Biotechnology
Transcriptome
Chemokines
Colorectal Neoplasms
Carcinogenesis
Adenocarcinoma
Multivariate Analysis
Biomarkers
Databases
Cytokines

Keywords

  • CCRT
  • Chemoradiotherapy
  • Dual oxidase 2
  • DUOX2
  • Rectal cancer

ASJC Scopus subject areas

  • Oncology

Cite this

High immunoreactivity of duox2 is associated with poor response to preoperative chemoradiation therapy and worse prognosis in rectal cancers. / Lin, Shih Chun; Chang, I. Wei; Hsieh, Pei Ling; Lin, Ching Yih; Sun, Ding Ping; Sheu, Ming Jen; Yang, Ching Chieh; Lin, Li Ching; He, Hong Lin; Tian, Yu Feng.

In: Journal of Cancer, Vol. 8, No. 14, 19545, 01.01.2017.

Research output: Contribution to journalArticle

Lin, Shih Chun ; Chang, I. Wei ; Hsieh, Pei Ling ; Lin, Ching Yih ; Sun, Ding Ping ; Sheu, Ming Jen ; Yang, Ching Chieh ; Lin, Li Ching ; He, Hong Lin ; Tian, Yu Feng. / High immunoreactivity of duox2 is associated with poor response to preoperative chemoradiation therapy and worse prognosis in rectal cancers. In: Journal of Cancer. 2017 ; Vol. 8, No. 14.
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abstract = "Purpose: Colorectal cancer is the third most common cancer and also the fourth most common cause of cancer mortality worldwide. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that DUOX2 was the most significantly up-regulated transcript among those related to cytokine and chemokine mediated signaling pathway (GO:0019221). Hence, the aim of this study was to assess the DUOX2 expression level and its clinicopathological correlation and prognostic significance in patients of rectal cancer. Materials and Methods: DUOX2 immunostain was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by radical proctectomy, which were divided into high- and low-expression subgroups. Furthermore, statistical analyses were examined to correlate the relationship between DUOX2 immunoreactivity and important clinical and pathological characteristics, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: DUOX2 overexpression was linked to post-CCRT tumor advancement, pre- and post-CCRT nodal metastasis and poor response to CCRT (all P ≤ 0.021). Furthermore, DUOX2 high expression was significantly associated with inferior DSS, LRFS and MeFS in univariate analysis (P ≤ 0.0097) and also served as an independent prognosticator indicating shorter DSS and LRFS interval in multivariate analysis (hazard ratio (HR) = 3.413, 95{\%} confidence interval (CI): 1.349-8.633; HR = 4.533, 95{\%} CI: 1.499-13.708, respectively). Conclusion: DUOX2 may play a pivotal role in carcinogenesis, tumor progression and response to neoadjuvant CCRT in rectal cancers, and serve as a novel prognostic biomarker. Additional researches to clarify the molecular and biochemical pathways are essential for developing promising DUOX2-targeted therapies for patients with rectal cancers.",
keywords = "CCRT, Chemoradiotherapy, Dual oxidase 2, DUOX2, Rectal cancer",
author = "Lin, {Shih Chun} and Chang, {I. Wei} and Hsieh, {Pei Ling} and Lin, {Ching Yih} and Sun, {Ding Ping} and Sheu, {Ming Jen} and Yang, {Ching Chieh} and Lin, {Li Ching} and He, {Hong Lin} and Tian, {Yu Feng}",
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T1 - High immunoreactivity of duox2 is associated with poor response to preoperative chemoradiation therapy and worse prognosis in rectal cancers

AU - Lin, Shih Chun

AU - Chang, I. Wei

AU - Hsieh, Pei Ling

AU - Lin, Ching Yih

AU - Sun, Ding Ping

AU - Sheu, Ming Jen

AU - Yang, Ching Chieh

AU - Lin, Li Ching

AU - He, Hong Lin

AU - Tian, Yu Feng

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Purpose: Colorectal cancer is the third most common cancer and also the fourth most common cause of cancer mortality worldwide. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that DUOX2 was the most significantly up-regulated transcript among those related to cytokine and chemokine mediated signaling pathway (GO:0019221). Hence, the aim of this study was to assess the DUOX2 expression level and its clinicopathological correlation and prognostic significance in patients of rectal cancer. Materials and Methods: DUOX2 immunostain was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by radical proctectomy, which were divided into high- and low-expression subgroups. Furthermore, statistical analyses were examined to correlate the relationship between DUOX2 immunoreactivity and important clinical and pathological characteristics, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: DUOX2 overexpression was linked to post-CCRT tumor advancement, pre- and post-CCRT nodal metastasis and poor response to CCRT (all P ≤ 0.021). Furthermore, DUOX2 high expression was significantly associated with inferior DSS, LRFS and MeFS in univariate analysis (P ≤ 0.0097) and also served as an independent prognosticator indicating shorter DSS and LRFS interval in multivariate analysis (hazard ratio (HR) = 3.413, 95% confidence interval (CI): 1.349-8.633; HR = 4.533, 95% CI: 1.499-13.708, respectively). Conclusion: DUOX2 may play a pivotal role in carcinogenesis, tumor progression and response to neoadjuvant CCRT in rectal cancers, and serve as a novel prognostic biomarker. Additional researches to clarify the molecular and biochemical pathways are essential for developing promising DUOX2-targeted therapies for patients with rectal cancers.

AB - Purpose: Colorectal cancer is the third most common cancer and also the fourth most common cause of cancer mortality worldwide. For rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) followed by radical proctectomy is gold standard treatment for patients with stage II/III rectal cancer. By data mining a documented database of rectal cancer transcriptome (GSE35452) from Gene Expression Omnibus, National Center of Biotechnology Information, we recognized that DUOX2 was the most significantly up-regulated transcript among those related to cytokine and chemokine mediated signaling pathway (GO:0019221). Hence, the aim of this study was to assess the DUOX2 expression level and its clinicopathological correlation and prognostic significance in patients of rectal cancer. Materials and Methods: DUOX2 immunostain was performed in 172 rectal adenocarcinomas treated with preoperative CCRT followed by radical proctectomy, which were divided into high- and low-expression subgroups. Furthermore, statistical analyses were examined to correlate the relationship between DUOX2 immunoreactivity and important clinical and pathological characteristics, as well as three survival indices: disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS). Results: DUOX2 overexpression was linked to post-CCRT tumor advancement, pre- and post-CCRT nodal metastasis and poor response to CCRT (all P ≤ 0.021). Furthermore, DUOX2 high expression was significantly associated with inferior DSS, LRFS and MeFS in univariate analysis (P ≤ 0.0097) and also served as an independent prognosticator indicating shorter DSS and LRFS interval in multivariate analysis (hazard ratio (HR) = 3.413, 95% confidence interval (CI): 1.349-8.633; HR = 4.533, 95% CI: 1.499-13.708, respectively). Conclusion: DUOX2 may play a pivotal role in carcinogenesis, tumor progression and response to neoadjuvant CCRT in rectal cancers, and serve as a novel prognostic biomarker. Additional researches to clarify the molecular and biochemical pathways are essential for developing promising DUOX2-targeted therapies for patients with rectal cancers.

KW - CCRT

KW - Chemoradiotherapy

KW - Dual oxidase 2

KW - DUOX2

KW - Rectal cancer

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