Overexpression of CPS1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy

doi:10.1007/s13277-014-2425-8

CNU IR > Pharmacy and Science > Dept. of Food & Drug Industry and Inspective Technology > Periodical Articles > Item 310902800/28641

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/28641

Title:	Overexpression of CPS1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy
Authors:	Lee, Yi-Ying Li, Chien-Feng Lin, Ching-Yih Lee, Sung-Wei Sheu, Ming-Jen Lin, Li-Ching Chen, Tzu-Ju Wu, Ting-Feng Hsing, Chung-Hsi
Contributors:	醫藥化學系
Keywords:	CPS1 Rectal cancer CCRT
Date:	2014-11
Issue Date:	2015-05-06 21:23:32 (UTC+8)
Publisher:	Springer
Abstract:	Locally advanced rectal cancers are currently treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery, but stratification of risk and final outcomes remain suboptimal. In view of the fact that glutamine metabolism is usually altered in cancer, we profiled and validated the significance of genes involved in this pathway in rectal cancers treated with CCRT. From a published transcriptome of rectal cancers (GSE35452), we focused on glutamine metabolic process-related genes (GO:0006541) and found upregulation of carbamoyl phosphate synthetase 1 (CPS1) gene most significantly predicted poor response to CCRT. We evaluated the expression levels of CPS1 using immunohistochemistry to analyze tumor specimens obtained during colonoscopy from 172 rectal cancer patients. Expression levels of CPS1 were further correlated with major clinicopathological features and survivals in this validation cohort. To further confirm CPS1 expression levels, Western blotting was performed for human colon epithelial primary cell (HCoEpiC) and four human colon cancer cells, including HT29, SW480, LoVo, and SW620. CPS1 overexpression was significantly related to advanced posttreatment tumor (T3, T4; P = 0.006) and nodal status (N1, N2; P < 0.001), and inferior tumor regression grade (P = 0.004). In survival analyses, CPS1 overexpression was significantly associated with shorter disease-specific survival (DSS) and metastasis-free survival (MeFS). Furthermore, using multivariate analysis, it was also independently predictive of worse DSS (P = 0.021, hazard ratio = 2.762) and MeFS (P = 0.004, hazard ratio = 3.897). CPS1 protein expression, as detected by Western blotting, is more abundant in colon cancer cells than nonneoplastic HCoEpiC. Overexpression of CPS1 is associated with poor therapeutic response and adverse outcomes among rectal cancer patients receiving CCRT, justifying the potential theranostic value of CPS1 for such patients.
Relation:	Tumor Biology, v.35 n.11, pp.11097-11105
Appears in Collections:	[Dept. of Food & Drug Industry and Inspective Technology] Periodical Articles

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