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

  • Research Article
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Tumor Biology

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.

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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

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Acknowledgments

This study is supported by the Chi Mei Medical Center (CMFHR10303 and CMNCKU10202) and Ministry of Health and Welfare (MOHW103-TD-B-111-05).

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Foundation Medical Center, Tainan, Taiwan

    Ching-Yih Lin & Ming-Jen Sheu

  2. Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University of Science and Technology, Tainan, Taiwan

    Ching-Yih Lin & Yi-Fong Wang

  3. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan

    Chien-Feng Li

  4. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

    Chien-Feng Li & Shang-Hung Chen

  5. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

    Chien-Feng Li

  6. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chien-Feng Li

  7. Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan, Taiwan

    Sung-Wei Lee

  8. Department of Radiation Oncology, Chi Mei Medical Center, Tainan, Taiwan

    Li-Ching Lin

  9. Division of Hematology and Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, No. 201, Taikang, Taikang Vil., Liouying Dist., Tainan City, 736, Taiwan

    Shang-Hung Chen

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  1. Ching-Yih Lin
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  2. Ming-Jen Sheu
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Correspondence to Shang-Hung Chen.

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Lin, CY., Sheu, MJ., Li, CF. et al. Deficiency in asparagine synthetase expression in rectal cancers receiving concurrent chemoradiotherapy: negative prognostic impact and therapeutic relevance. Tumor Biol. 35, 6823–6830 (2014). https://doi.org/10.1007/s13277-014-1895-z

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  • DOI: https://doi.org/10.1007/s13277-014-1895-z

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