Overexpression of transcobalamin 1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy

Yi Ying Lee, Yu Ching Wei, Yu Feng Tian, Ding Ping Sun, Ming Jen Sheu, Ching Chieh Yang, Li Ching Lin, Chen Yi Lin, Chung Hsi Hsing, Wan Shan Li, Chien Feng Li, Pei Ling Hsieh, Ching Yih Lin

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

Original languageEnglish
Pages (from-to)1330-1337
Number of pages8
JournalJournal of Cancer
Volume8
Issue number8
DOIs
Publication statusPublished - 2017
Externally publishedYes

Fingerprint

Transcobalamins
Chemoradiotherapy
Rectal Neoplasms
Survival
Neoplasm Metastasis
Neoplasms
Breast Neoplasms
Data Mining
Ion Transport
Therapeutics
Vitamin B 12
Survival Analysis
Transcriptome

Keywords

  • CCRT
  • Chemoradiotherapy
  • Rectal cancer
  • TCN1
  • Transcobalamin 1

ASJC Scopus subject areas

  • Oncology

Cite this

Overexpression of transcobalamin 1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy. / Lee, Yi Ying; Wei, Yu Ching; Tian, Yu Feng; Sun, Ding Ping; Sheu, Ming Jen; Yang, Ching Chieh; Lin, Li Ching; Lin, Chen Yi; Hsing, Chung Hsi; Li, Wan Shan; Li, Chien Feng; Hsieh, Pei Ling; Lin, Ching Yih.

In: Journal of Cancer, Vol. 8, No. 8, 2017, p. 1330-1337.

Research output: Contribution to journalArticle

Lee, YY, Wei, YC, Tian, YF, Sun, DP, Sheu, MJ, Yang, CC, Lin, LC, Lin, CY, Hsing, CH, Li, WS, Li, CF, Hsieh, PL & Lin, CY 2017, 'Overexpression of transcobalamin 1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy', Journal of Cancer, vol. 8, no. 8, pp. 1330-1337. https://doi.org/10.7150/jca.18274
Lee, Yi Ying ; Wei, Yu Ching ; Tian, Yu Feng ; Sun, Ding Ping ; Sheu, Ming Jen ; Yang, Ching Chieh ; Lin, Li Ching ; Lin, Chen Yi ; Hsing, Chung Hsi ; Li, Wan Shan ; Li, Chien Feng ; Hsieh, Pei Ling ; Lin, Ching Yih. / Overexpression of transcobalamin 1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy. In: Journal of Cancer. 2017 ; Vol. 8, No. 8. pp. 1330-1337.
@article{897c8f22aeac46978c21f62bd7dc2cad,
title = "Overexpression of transcobalamin 1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy",
abstract = "Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.",
keywords = "CCRT, Chemoradiotherapy, Rectal cancer, TCN1, Transcobalamin 1",
author = "Lee, {Yi Ying} and Wei, {Yu Ching} and Tian, {Yu Feng} and Sun, {Ding Ping} and Sheu, {Ming Jen} and Yang, {Ching Chieh} and Lin, {Li Ching} and Lin, {Chen Yi} and Hsing, {Chung Hsi} and Li, {Wan Shan} and Li, {Chien Feng} and Hsieh, {Pei Ling} and Lin, {Ching Yih}",
year = "2017",
doi = "10.7150/jca.18274",
language = "English",
volume = "8",
pages = "1330--1337",
journal = "Journal of Cancer",
issn = "1837-9664",
publisher = "Ivyspring International Publisher",
number = "8",

}

TY - JOUR

T1 - Overexpression of transcobalamin 1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy

AU - Lee, Yi Ying

AU - Wei, Yu Ching

AU - Tian, Yu Feng

AU - Sun, Ding Ping

AU - Sheu, Ming Jen

AU - Yang, Ching Chieh

AU - Lin, Li Ching

AU - Lin, Chen Yi

AU - Hsing, Chung Hsi

AU - Li, Wan Shan

AU - Li, Chien Feng

AU - Hsieh, Pei Ling

AU - Lin, Ching Yih

PY - 2017

Y1 - 2017

N2 - Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

AB - Objective: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an increasingly common therapeutic strategy for locally advanced rectal cancer, but stratification of risk and final outcomes remain a major challenge. Transcobalamin 1 (TCN1), a vitamin B12 (cobalamin)-binding protein, regulates cobalamin homeostasis. High expression of TCN1 have been reported in neoplasms such as breast cancer and hepatocellular carcinoma. However, little is known about the relevance of TCN1 to rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of TCN1 expression in patients with rectal cancer following neoadjuvant CCRT. Methods: Through data mining from a published transcriptome of rectal cancers (GSE35452), we identified upregulation of TCN1 gene as the most significantly predicted poor response to CCRT among ion transport-related genes (GO:0006811). We evaluated TCN1 immunohistochemistry and performed an H-score analysis on endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery. Expression levels of TCN1 were further correlated with clinicopathologic features, therapeutic response, tumor regression grade (TRG) and survivals including metastasis-free survival (MeFS), disease-specific survival (DSS) and recurrent-free survival (LRFS). Results: TCN1 overexpression was significantly related to advanced post-treatment tumor (T3, T4; p<0.001) and nodal status (N1, N2; p<0.001), vascular invasion (p=0.003) and inferior tumor regression grade (p < 0.001). In survival analyses, TCN1 overexpression was significantly associated with shorter DSS (p<0.0001), MeFS (p=0.0002) and LRFS (p=0.0001). Furthermore, it remained an independent prognosticator of worse DSS (p=0.002, hazard ratio=3.344), MeFS (p=0.021, hazard ratio=3.015) and LRFS (p=0.037, hazard ratio=3.037) in the multivariate comparison. Conclusion: Overexpression of TCN1 is associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT, justifying the potential prognostic value of TCN1 in rectal cancer receiving CCRT.

KW - CCRT

KW - Chemoradiotherapy

KW - Rectal cancer

KW - TCN1

KW - Transcobalamin 1

UR - http://www.scopus.com/inward/record.url?scp=85019954537&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019954537&partnerID=8YFLogxK

U2 - 10.7150/jca.18274

DO - 10.7150/jca.18274

M3 - Article

VL - 8

SP - 1330

EP - 1337

JO - Journal of Cancer

JF - Journal of Cancer

SN - 1837-9664

IS - 8

ER -