High expression of EphA4 predicted lesser degree of tumor regression after neoadjuvant chemoradiotherapy in rectal cancer

Ching Yih Lin, Ying En Lee, Yu Feng Tian, Ding Ping Sun, Ming Jen Sheu, Chen Yi Lin, Chien Feng Li, Sung Wei Lee, Li Ching Lin, I. Wei Chang, Chieh Tien Wang, Hong Lin He

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression.Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed.Results: EphA4 expression was significantly associated with vascular invasion (P=0.015), post-treatment depth of tumor invasion (P=0.006), pre-treatment and post-treatment lymph node metastasis (P=0.004 and P=0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT (P=0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival (P=0.0009) and metastasis-free survival (P=0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P=0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P=0.003).Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.

Original languageEnglish
Pages (from-to)1089-1096
Number of pages8
JournalJournal of Cancer
Volume8
Issue number6
DOIs
Publication statusPublished - Apr 9 2017
Externally publishedYes

Fingerprint

EphA1 Receptor
Chemoradiotherapy
Rectal Neoplasms
Neoplasms
Survival
Neoplasm Metastasis
Receptor Protein-Tyrosine Kinases
Therapeutics
Blood Vessels
Multivariate Analysis
Lymph Nodes

Keywords

  • CCRT
  • Chemoradiotherapy
  • EphA4
  • Rectal cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Lin, C. Y., Lee, Y. E., Tian, Y. F., Sun, D. P., Sheu, M. J., Lin, C. Y., ... He, H. L. (2017). High expression of EphA4 predicted lesser degree of tumor regression after neoadjuvant chemoradiotherapy in rectal cancer. Journal of Cancer, 8(6), 1089-1096. https://doi.org/10.7150/jca.17471

High expression of EphA4 predicted lesser degree of tumor regression after neoadjuvant chemoradiotherapy in rectal cancer. / Lin, Ching Yih; Lee, Ying En; Tian, Yu Feng; Sun, Ding Ping; Sheu, Ming Jen; Lin, Chen Yi; Li, Chien Feng; Lee, Sung Wei; Lin, Li Ching; Chang, I. Wei; Wang, Chieh Tien; He, Hong Lin.

In: Journal of Cancer, Vol. 8, No. 6, 09.04.2017, p. 1089-1096.

Research output: Contribution to journalArticle

Lin, CY, Lee, YE, Tian, YF, Sun, DP, Sheu, MJ, Lin, CY, Li, CF, Lee, SW, Lin, LC, Chang, IW, Wang, CT & He, HL 2017, 'High expression of EphA4 predicted lesser degree of tumor regression after neoadjuvant chemoradiotherapy in rectal cancer', Journal of Cancer, vol. 8, no. 6, pp. 1089-1096. https://doi.org/10.7150/jca.17471
Lin, Ching Yih ; Lee, Ying En ; Tian, Yu Feng ; Sun, Ding Ping ; Sheu, Ming Jen ; Lin, Chen Yi ; Li, Chien Feng ; Lee, Sung Wei ; Lin, Li Ching ; Chang, I. Wei ; Wang, Chieh Tien ; He, Hong Lin. / High expression of EphA4 predicted lesser degree of tumor regression after neoadjuvant chemoradiotherapy in rectal cancer. In: Journal of Cancer. 2017 ; Vol. 8, No. 6. pp. 1089-1096.
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abstract = "Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression.Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed.Results: EphA4 expression was significantly associated with vascular invasion (P=0.015), post-treatment depth of tumor invasion (P=0.006), pre-treatment and post-treatment lymph node metastasis (P=0.004 and P=0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT (P=0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival (P=0.0009) and metastasis-free survival (P=0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95{\%} CI, 1.131-5.651; P=0.024) and metastasis-free survival (HR, 3.908; 95{\%} CI, 1.590-9.601; P=0.003).Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.",
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T1 - High expression of EphA4 predicted lesser degree of tumor regression after neoadjuvant chemoradiotherapy in rectal cancer

AU - Lin, Ching Yih

AU - Lee, Ying En

AU - Tian, Yu Feng

AU - Sun, Ding Ping

AU - Sheu, Ming Jen

AU - Lin, Chen Yi

AU - Li, Chien Feng

AU - Lee, Sung Wei

AU - Lin, Li Ching

AU - Chang, I. Wei

AU - Wang, Chieh Tien

AU - He, Hong Lin

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N2 - Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression.Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed.Results: EphA4 expression was significantly associated with vascular invasion (P=0.015), post-treatment depth of tumor invasion (P=0.006), pre-treatment and post-treatment lymph node metastasis (P=0.004 and P=0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT (P=0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival (P=0.0009) and metastasis-free survival (P=0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P=0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P=0.003).Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.

AB - Background: Numerous transmembrane receptor tyrosine kinase pathways have been found to play an important role in tumor progression in some cancers. This study was aimed to evaluate the clinical impact of Eph receptor A4 (EphA4) in patients with rectal cancer treated with neoadjuvant concurrent chemoradiotherapy (CCRT) combined with mesorectal excision, with special emphasis on tumor regression.Methods: Analysis of the publicly available expression profiling dataset of rectal cancer disclosed that EphA4 was the top-ranking, significantly upregulated, transmembrane receptor tyrosine kinase pathway-associated gene in the non-responders to CCRT, compared with the responders. Immunohistochemical study was conducted to assess the EphA4 expression in pre-treatment biopsy specimens from 172 rectal cancer patients without distant metastasis. The relationships between EphA4 expression and various clinicopathological factors or survival were statistically analyzed.Results: EphA4 expression was significantly associated with vascular invasion (P=0.015), post-treatment depth of tumor invasion (P=0.006), pre-treatment and post-treatment lymph node metastasis (P=0.004 and P=0.011, respectively). More importantly, high EphA4 expression was significantly predictive for lesser degree of tumor regression after CCRT (P=0.031). At univariate analysis, high EphA4 expression was a negative prognosticator for disease-specific survival (P=0.0009) and metastasis-free survival (P=0.0001). At multivariate analysis, high expression of EphA4 still served as an independent adverse prognostic factor for disease-specific survival (HR, 2.528; 95% CI, 1.131-5.651; P=0.024) and metastasis-free survival (HR, 3.908; 95% CI, 1.590-9.601; P=0.003).Conclusion: High expression of EphA4 predicted lesser degree of tumor regression after CCRT and served as an independent negative prognostic factor in patients with rectal cancer.

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KW - Chemoradiotherapy

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KW - Rectal cancer

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