Tumor Biology

, Volume 35, Issue 7, pp 6823–6830

Deficiency in asparagine synthetase expression in rectal cancers receiving concurrent chemoradiotherapy: negative prognostic impact and therapeutic relevance

  • Ching-Yih Lin
  • Ming-Jen Sheu
  • Chien-Feng Li
  • Sung-Wei Lee
  • Li-Ching Lin
  • Yi-Fong Wang
  • Shang-Hung Chen
Research Article

DOI: 10.1007/s13277-014-1895-z

Cite this article as:
Lin, CY., Sheu, MJ., Li, CF. et al. Tumor Biol. (2014) 35: 6823. doi:10.1007/s13277-014-1895-z

Abstract

Locally advanced rectal cancers are currently treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery, but risk stratification and final outcomes remain suboptimal. In this study, we identify and validate targetable metabolic drivers relevant to the prognosis of patients with rectal cancer treated with CCRT. Using a published transcriptome of rectal cancers, we found that asparagine synthetase (ASNS) gene significantly predicted the response to CCRT. From 172 patients with rectal cancer, the expression levels of ASNS, using immunohistochemistry assays, were further evaluated in tumor specimens initially obtained by using colonoscopy. Expression levels of ASNS were further correlated with major clinicopathological features and clinical survivals in this valid cohort. ASNS deficiency was significantly related to advanced posttreatment tumor (T3, T4; P = .015) and nodal status (N1, N2; P = .004) and inferior tumor regression grade (P < .001). In survival analyses, ASNS deficiency was significantly associated with shorter local recurrence-free survival (LRFS; P = .0039), metastasis-free survival (MeFS; P = .0001), and disease-specific survival (DSS; P = .0006). Furthermore, ASNS deficiency was independently predictive of worse outcomes for MeFS (P = .012, hazard ratio = 3.691) and DSS (P = .022, hazard ratio = 2.845), using multivariate analysis. ASNS deficiency is correlated with poor therapeutic response and worse survivals in patients with rectal cancer receiving neoadjuvant CCRT. These findings indicate that ASNS is a prognostic factor with therapeutic potential for treating rectal cancer.

Keywords

ASNSRectal CancerCCRT

Abbreviations

CCRT

Chemoradiotherapy

ASNS

Asparagine synthetase

LRFS

Local recurrence-free survival

MeFS

Metastasis-free survival

DSS

Disease-specific survival

LARC

Locally advanced rectal cancer

ALL

Acute lymphoblastic leukemia

Pre-Tx

Pre-treatment

Post-Tx

Post-treatment

AJCC

American Joint Committee on Cancer

TRG

Tumor regression grade

HR

Hazard ratio

PAH

Phenylalanine hydroxylase

HCC

Hepatocellular carcinoma

NPC

Nasopharyngeal carcinoma

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ching-Yih Lin
    • 1
    • 2
  • Ming-Jen Sheu
    • 1
  • Chien-Feng Li
    • 3
    • 4
    • 5
    • 6
  • Sung-Wei Lee
    • 7
  • Li-Ching Lin
    • 8
  • Yi-Fong Wang
    • 2
  • Shang-Hung Chen
    • 4
    • 9
  1. 1.Division of Gastroenterology and Hepatology, Department of Internal MedicineChi Mei Foundation Medical CenterTainanTaiwan
  2. 2.Department of Leisure, Recreation, and Tourism ManagementSouthern Taiwan University of Science and TechnologyTainanTaiwan
  3. 3.Department of PathologyChi Mei Medical CenterTainanTaiwan
  4. 4.National Institute of Cancer ResearchNational Health Research InstitutesTainanTaiwan
  5. 5.Department of BiotechnologySouthern Taiwan University of Science and TechnologyTainanTaiwan
  6. 6.Institute of Clinical MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  7. 7.Department of Radiation OncologyChi Mei Medical CenterTainanTaiwan
  8. 8.Department of Radiation OncologyChi Mei Medical CenterTainanTaiwan
  9. 9.Division of Hematology and Oncology, Department of Internal MedicineChi Mei Medical Center, LiouyingTainan CityTaiwan