Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/31688
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    Title: Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy
    Authors: 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
    Contributors: Chi Mei Med Ctr, Dept Pathol
    Natl Sun Yat Sen Univ, Inst Biomed Sci
    Kaohsiung Municipal Tatung Hosp, Dept Pathol
    Chi Mei Med Ctr, Dept Surg, Div Gen Surg
    Chia Nan Univ Pharm & Sci, Dept Hlth & Nutr
    Chia Nan Univ Pharm & Sci, Dept Pharm
    Chi Mei Med Ctr, Dept Internal Med, Div Gastroenterol & Hepatol
    Chi Mei Med Ctr, Dept Radiat Oncol
    Chi Mei Med Ctr, Dept Anesthesiol
    Kaohsiung Med Univ,Kaohsiung Med Univ Hosp, Dept Pathol
    Chi Mei Med Ctr, Dept Pathol
    Natl Hlth Res Inst, Natl Inst Canc Res
    Southern Taiwan Univ Sci & Technol, Dept Biotechnol
    Chi Mei Med Ctr, Dept Med Image
    Dept Leisure Recreat & Tourism Management
    Keywords: TCN1
    Transcobalamin 1
    CCRT
    chemoradiotherapy
    rectal cancer
    Date: 2017
    Issue Date: 2018-11-30 15:52:56 (UTC+8)
    Publisher: Ivyspring Int Publ
    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.
    Relation: Journal of Cancer, v.8, n.8, pp.1330-1337
    Appears in Collections:[Dept. of Pharmacy] Periodical Articles
    [Dept. of Health and Nutrition (including master's program)] Periodical Articles

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