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Rsf-1 expression in rectal cancer: with special emphasis on the independent prognostic value after neoadjuvant chemoradiation
  1. Ching-Yih Lin1,2,
  2. Yu-Feng Tian3,4,
  3. Li-Ching Wu5,
  4. Li-Tzong Chen6,
  5. Li-Ching Lin7,
  6. Chung-Hsi Hsing8,
  7. Sung-Wei Lee9,
  8. Ming-Jen Sheu1,
  9. Hao-Hsien Lee10,
  10. Yu-Hui Wang11,
  11. Yow-Ling Shiue12,
  12. Wen-Ren Wu12,
  13. Hsuan-Ying Huang13,
  14. Han-Ping Hsu14,
  15. Chien-Feng Li5,6,12,15,16,
  16. Shang-Hung Chen6,17,18
  1. 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
  2. 2Departments of Nursing and Nutrition & Health Science, Chang Jung Christian University, Tainan, Taiwan
  3. 3Division of General Surgery, Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan
  4. 4Department of Health and Nutrition, Chia Nan University of Pharmacy and Science
  5. 5Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan
  6. 6National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
  7. 7Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan
  8. 8Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan
  9. 9Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan
  10. 10Department of Surgery, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
  11. 11Institute of Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan
  12. 12Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan
  13. 13Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
  14. 14College of Medicine, China Medical University, Taichung, Taiwan
  15. 15Department of Biotechnology, Southern Taiwan University, Tainan, Taiwan
  16. 16Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan
  17. 17Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
  18. 18Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
  1. Correspondence to Dr Shang-Hung Chen, Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan; bryanchen0615{at}


Aims Neoadjuvant chemoradiation therapy (CRT) is an increasingly used therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcome after CRT. Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness and predicts therapeutic response in certain carcinomas. However, the expression of Rsf-1 has never been reported in rectal cancer. This study examined the predictive and prognostic impacts of Rsf-1 expression in patients with rectal cancer following neoadjuvant CRT.

Methods Rsf-1 immunoexpression was retrospectively assessed for pre-treatment biopsies of 172 rectal cancer patients without initial distant metastasis. All of them were treated with neoadjuvant CRT followed by surgery. The results were correlated with the clinicopathological features, therapeutic response, tumour regression grade and metastasis-free survival (MeFS), local recurrent-free survival and disease-specific survival.

Results Present in 82 cases (47.7%), high-expression of Rsf-1 was associated with advanced pre-treatment tumour status (T3, T4, p=0.020), advanced post-treatment tumour status (T3, T4, p<0.001) and inferior tumour regression grade (p=0.028). Of note, high-expression of Rsf-1 emerged as an adverse prognosticator for diseases-specific survival (p=0.0092) and significantly predicted worse MeFS (p=0.0006). Moreover, high-expression of Rsf-1 also remained prognostic independent for worse MeFS (HR 2.834; p=0.0214).

Conclusions High-expression of Rsf-1 is associated with poor therapeutic response and adverse outcome in rectal cancer patients treated with neoadjuvant CRT, which confers tumour aggressiveness and therapeutic resistance through chromatin remodelling and represents a potential prognostic biomarker in rectal cancer.

  • Rsf-1
  • rectal cancer
  • neoadjuvant chemoradiation
  • cancer
  • oncogenes
  • molecular oncology
  • molecular pathology
  • molecular genetics
  • tumour biology
  • tumour markers
  • cancer research

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  • Additional supplementary materials are published online only. To view these files please visit the journal online (

  • CYL and YFT contributed equally to this work.

  • Funding This work was supported in part by grants from Chi-Mei Medical Center (CMFHR10044) and Department of Health, Taiwan (DOH99-TD-C-111-004).

  • Competing interests None.

  • Patient consent The current study used tumour materials from the Biobank of Chi-Mei Medical Center. As a rule, all tumour samples are collected only when patient consent is completed. Once being enrolled, the samples are disconnected with identifiable private information and thus no more patient consent is needed.

  • Ethics approval The institutional review board had approved procurement of formalin-fixed tissue of 172 LARC patients for this study (IRB 10009-L04).

  • Provenance and peer review Not commissioned; externally peer reviewed.