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

Yi Ying Lee, Chien Feng Li, Ching Yih Lin, Sung Wei Lee, Ming Jen Sheu, Li Ching Lin, Tzu Ju Chen, Ting Feng Wu, Chung Hsi Hsing

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11097-11105
Number of pages9
JournalTumor Biology
Volume35
Issue number11
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Carbamyl Phosphate
Chemoradiotherapy
Ligases
Rectal Neoplasms
Survival
Glutamine
Colonic Neoplasms
Neoplasms
Colon
Western Blotting
Epithelial Cells
Neoplasm Metastasis
Genes
HT29 Cells
Colonoscopy
Survival Analysis
Transcriptome
Up-Regulation
Multivariate Analysis
Immunohistochemistry

Keywords

  • CCRT
  • CPS1
  • Rectal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

Cite this

Lee, Y. Y., Li, C. F., Lin, C. Y., Lee, S. W., Sheu, M. J., Lin, L. C., ... Hsing, C. H. (2014). Overexpression of CPS1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy. Tumor Biology, 35(11), 11097-11105. https://doi.org/10.1007/s13277-014-2425-8

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

In: Tumor Biology, Vol. 35, No. 11, 2014, p. 11097-11105.

Research output: Contribution to journalArticle

Lee, YY, Li, CF, Lin, CY, Lee, SW, Sheu, MJ, Lin, LC, Chen, TJ, Wu, TF & Hsing, CH 2014, 'Overexpression of CPS1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy', Tumor Biology, vol. 35, no. 11, pp. 11097-11105. https://doi.org/10.1007/s13277-014-2425-8
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. / Overexpression of CPS1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy. In: Tumor Biology. 2014 ; Vol. 35, No. 11. pp. 11097-11105.
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