Associations of Rsf-1 overexpression with poor therapeutic response and worse survival in patients with nasopharyngeal carcinoma
- Hui-Chun Tai1,2,
- Hsuan-Ying Huang3,
- Sung-Wei Lee4,
- Ching-Yih Lin5,
- Ming-Jen Sheu5,
- Shih-Lun Chang6,
- Li-Ching Wu7,
- Yow-Ling Shiue8,
- Wen-Ren Wu8,
- Chun-Mao Lin9,
- Chien-Feng Li7,8,10,11
- 1Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan
- 2Institute of Clinical Medicine, Kaohsiung Medical University
- 3Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- 4Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
- 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan
- 6Department of Otolaryngology, Chi-Mei Medical Center, Tainan, Taiwan
- 7Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan
- 8Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan
- 9College of Medicine, Taipei Medical University, Taipei, Taiwan
- 10National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
- 11Department of Biotechnology, Southern Taiwan University, Tainan, Taiwan
- Correspondence to Chien-Feng Li, Department of Pathology, Chi-Mei Foundation Medical Center, 901 Chunghwa Road, City, Tainan County 710, Yung Kang 710, Tainan, Taiwan;
Contributors Conception and design: HYH, CFL, SLC, CML. Analysis and interpretation of data: HCT, SWL, CYL, WRW. Drafting the article: HCT, MJS. Final approval: LCW, YLS. HCT, HYH and CML contributed equally to this work.
- Accepted 12 October 2011
- Published Online First 12 November 2011
Aims Deregulated chromatin remodelling often leads to aberrant gene expression in cells, thereby implicating tumour development and progression. As a subunit of remodelling and spacing factor complex, Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness in common carcinomas. However, the expression of Rsf-1 has never been reported in nasopharyngeal carcinoma (NPC). This study aimed at evaluating the expression status, associations with clincopathological variables and prognostic implications of Rsf-1 in a well-defined cohort of NPC.
Methods Rsf-1 immunoexpression was retrospectively assessed in biopsies of 108 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The results were correlated with the clinicopathological features, therapeutic response, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-specific survival (DSS).
Results Present in 49 cases (45%), Rsf-1 overexpression was associated with N2,3 status (p=0.016), American Joint Committee on Cancer stage 3, 4 (p=0.004), and incomplete therapeutic response (p=0.041). In multivariate analyses, Rsf-1 overexpression not only emerged as the sole independent adverse prognosticator for LRFS (p=0.0002, RR 5.287) but also independently predicted worse DMFS (p=0.0011, RR 3.185) and DSS (p<0.0001, RR 4.442), along with T3,4 (p=0.0454) and N2,3 (p=0.0319), respectively.
Conclusion Rsf-1 overexpression is common and is associated with adverse prognosticators and therapeutic response, which confers tumour aggressiveness through chromatin remodelling, and represents a potential prognostic biomarker in NPC.
- bone pathology
- breast pathology
- chromatin remodelling
- molecular genetics
- molecular oncology
- molecular pathology
HCT and HYH contributed equally to this work.
Funding This work was supported in part by grants from Chi-Mei Medical Center (99-CM-TMU-03) and Department of Health, Taiwan (DOH99-TD-C-111-004).
Competing interests None.
Ethics approval Ethics approval was provided by the institutional review board, who had approved the procurement of formalin-fixed tissue and further immunohistochemical study of nasopharyngeal carcinoma for this paper (IRB100-09-003).
Provenance and peer review Not commissioned; externally peer reviewed.