Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy

doi:10.7150/jca.18274

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標題:	Overexpression of Transcobalamin 1 is an Independent Negative Prognosticator in Rectal Cancers Receiving Concurrent Chemoradiotherapy
作者:	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
貢獻者:	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
關鍵字:	TCN1 Transcobalamin 1 CCRT chemoradiotherapy rectal cancer
日期:	2017
上傳時間:	2018-11-30 15:52:56 (UTC+8)
出版者:	Ivyspring Int Publ
摘要:	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.
關聯:	Journal of Cancer, v.8, n.8, pp.1330-1337
显示于类别:	[藥學系(所)] 期刊論文 [保健營養系(所) ] 期刊論文

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