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

研究成果: 雜誌貢獻文章同行評審

13 引文 斯高帕斯(Scopus)

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.

原文英語
頁(從 - 到)1330-1337
頁數8
期刊Journal of Cancer
8
發行號8
DOIs
出版狀態已發佈 - 2017
對外發佈

ASJC Scopus subject areas

  • 腫瘤科

指紋

深入研究「Overexpression of transcobalamin 1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy」主題。共同形成了獨特的指紋。

引用此