Overexpression of REG4 confers an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy

Hong Lin He, Ying En Lee, Yow Ling Shiue, Sung Wei Lee, Li Ching Lin, Tzu Ju Chen, Ting Feng Wu, Chung-Hsi Hsing, Hsuan Ying Huang, Jaw Yuan Wang, Chien Feng Li

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background and Objectives: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Through data mining from published transcriptomic database, we identified Regenerating Gene Type IV (REG4) as the most significantly associated gene with resistance to CCRT. This study examined the prognostic impact of REG4 expression in patients with rectal cancer receiving neoadjuvant CCRT.

Methods: REG4 immunohistochemistry was retrospectively assessed for pre-treatment biopsy specimens from 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery without initial distant metastasis. The results were correlated with the clinicopathological variables, disease-specific survival (DSS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS), as well as g-H2AX expression in post-treatment tumor samples.

Results: High expression of REG4 was associated with advanced pre-treatment nodal status (P.0.026), advanced post-treatment tumor status (P.0.006), advanced post-treatment nodal status (P.0.001), advanced post-treatment tumor stage (P 0.001), and inferior tumor regression grade (P.0.001). Of note, high expression of REG4 emerged as an adverse prognosticator for DSS (P.0.0004), LRFS (P.0.0009), and MeFS (P.0.0254). After multivariate comparisons, it remained independently prognostic for worse DSS (hazard ratio [HR].2.731; P.0.025) and LRFS (HR.2.676; P.0.029). High expression of REG4 was also negatively associated with g-H2AX expression (P 0.0001, r.-0.708).

Conclusions: High expression of REG4 is associated with poor therapeutic response, adverse outcome and an aggressive phenotype in rectal cancer patients treated with neoadjuvant CCRT, justifying REG4 is a surrogate marker to predict CCRT resistance.

Original languageEnglish
Pages (from-to)1002-1010
Number of pages9
JournalJournal of Surgical Oncology
Volume110
Issue number8
DOIs
Publication statusPublished - Dec 1 2014
Externally publishedYes

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Chemoradiotherapy
Rectal Neoplasms
Survival
Therapeutics
Recurrence
Neoplasms
Neoplasm Metastasis
Data Mining
Genes
Biomarkers
Immunohistochemistry
Databases
Phenotype
Biopsy

Keywords

  • CCRT
  • Rectal cancer
  • REG4

ASJC Scopus subject areas

  • Surgery
  • Oncology
  • Medicine(all)

Cite this

Overexpression of REG4 confers an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy. / He, Hong Lin; Lee, Ying En; Shiue, Yow Ling; Lee, Sung Wei; Lin, Li Ching; Chen, Tzu Ju; Wu, Ting Feng; Hsing, Chung-Hsi; Huang, Hsuan Ying; Wang, Jaw Yuan; Li, Chien Feng.

In: Journal of Surgical Oncology, Vol. 110, No. 8, 01.12.2014, p. 1002-1010.

Research output: Contribution to journalArticle

He, HL, Lee, YE, Shiue, YL, Lee, SW, Lin, LC, Chen, TJ, Wu, TF, Hsing, C-H, Huang, HY, Wang, JY & Li, CF 2014, 'Overexpression of REG4 confers an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy', Journal of Surgical Oncology, vol. 110, no. 8, pp. 1002-1010. https://doi.org/10.1002/jso.23764
He, Hong Lin ; Lee, Ying En ; Shiue, Yow Ling ; Lee, Sung Wei ; Lin, Li Ching ; Chen, Tzu Ju ; Wu, Ting Feng ; Hsing, Chung-Hsi ; Huang, Hsuan Ying ; Wang, Jaw Yuan ; Li, Chien Feng. / Overexpression of REG4 confers an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy. In: Journal of Surgical Oncology. 2014 ; Vol. 110, No. 8. pp. 1002-1010.
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abstract = "Background and Objectives: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Through data mining from published transcriptomic database, we identified Regenerating Gene Type IV (REG4) as the most significantly associated gene with resistance to CCRT. This study examined the prognostic impact of REG4 expression in patients with rectal cancer receiving neoadjuvant CCRT.Methods: REG4 immunohistochemistry was retrospectively assessed for pre-treatment biopsy specimens from 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery without initial distant metastasis. The results were correlated with the clinicopathological variables, disease-specific survival (DSS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS), as well as g-H2AX expression in post-treatment tumor samples.Results: High expression of REG4 was associated with advanced pre-treatment nodal status (P.0.026), advanced post-treatment tumor status (P.0.006), advanced post-treatment nodal status (P.0.001), advanced post-treatment tumor stage (P 0.001), and inferior tumor regression grade (P.0.001). Of note, high expression of REG4 emerged as an adverse prognosticator for DSS (P.0.0004), LRFS (P.0.0009), and MeFS (P.0.0254). After multivariate comparisons, it remained independently prognostic for worse DSS (hazard ratio [HR].2.731; P.0.025) and LRFS (HR.2.676; P.0.029). High expression of REG4 was also negatively associated with g-H2AX expression (P 0.0001, r.-0.708).Conclusions: High expression of REG4 is associated with poor therapeutic response, adverse outcome and an aggressive phenotype in rectal cancer patients treated with neoadjuvant CCRT, justifying REG4 is a surrogate marker to predict CCRT resistance.",
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T1 - Overexpression of REG4 confers an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy

AU - He, Hong Lin

AU - Lee, Ying En

AU - Shiue, Yow Ling

AU - Lee, Sung Wei

AU - Lin, Li Ching

AU - Chen, Tzu Ju

AU - Wu, Ting Feng

AU - Hsing, Chung-Hsi

AU - Huang, Hsuan Ying

AU - Wang, Jaw Yuan

AU - Li, Chien Feng

PY - 2014/12/1

Y1 - 2014/12/1

N2 - Background and Objectives: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Through data mining from published transcriptomic database, we identified Regenerating Gene Type IV (REG4) as the most significantly associated gene with resistance to CCRT. This study examined the prognostic impact of REG4 expression in patients with rectal cancer receiving neoadjuvant CCRT.Methods: REG4 immunohistochemistry was retrospectively assessed for pre-treatment biopsy specimens from 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery without initial distant metastasis. The results were correlated with the clinicopathological variables, disease-specific survival (DSS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS), as well as g-H2AX expression in post-treatment tumor samples.Results: High expression of REG4 was associated with advanced pre-treatment nodal status (P.0.026), advanced post-treatment tumor status (P.0.006), advanced post-treatment nodal status (P.0.001), advanced post-treatment tumor stage (P 0.001), and inferior tumor regression grade (P.0.001). Of note, high expression of REG4 emerged as an adverse prognosticator for DSS (P.0.0004), LRFS (P.0.0009), and MeFS (P.0.0254). After multivariate comparisons, it remained independently prognostic for worse DSS (hazard ratio [HR].2.731; P.0.025) and LRFS (HR.2.676; P.0.029). High expression of REG4 was also negatively associated with g-H2AX expression (P 0.0001, r.-0.708).Conclusions: High expression of REG4 is associated with poor therapeutic response, adverse outcome and an aggressive phenotype in rectal cancer patients treated with neoadjuvant CCRT, justifying REG4 is a surrogate marker to predict CCRT resistance.

AB - Background and Objectives: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Through data mining from published transcriptomic database, we identified Regenerating Gene Type IV (REG4) as the most significantly associated gene with resistance to CCRT. This study examined the prognostic impact of REG4 expression in patients with rectal cancer receiving neoadjuvant CCRT.Methods: REG4 immunohistochemistry was retrospectively assessed for pre-treatment biopsy specimens from 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery without initial distant metastasis. The results were correlated with the clinicopathological variables, disease-specific survival (DSS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS), as well as g-H2AX expression in post-treatment tumor samples.Results: High expression of REG4 was associated with advanced pre-treatment nodal status (P.0.026), advanced post-treatment tumor status (P.0.006), advanced post-treatment nodal status (P.0.001), advanced post-treatment tumor stage (P 0.001), and inferior tumor regression grade (P.0.001). Of note, high expression of REG4 emerged as an adverse prognosticator for DSS (P.0.0004), LRFS (P.0.0009), and MeFS (P.0.0254). After multivariate comparisons, it remained independently prognostic for worse DSS (hazard ratio [HR].2.731; P.0.025) and LRFS (HR.2.676; P.0.029). High expression of REG4 was also negatively associated with g-H2AX expression (P 0.0001, r.-0.708).Conclusions: High expression of REG4 is associated with poor therapeutic response, adverse outcome and an aggressive phenotype in rectal cancer patients treated with neoadjuvant CCRT, justifying REG4 is a surrogate marker to predict CCRT resistance.

KW - CCRT

KW - Rectal cancer

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