J Cancer 2017; 8(9):1647-1654. doi:10.7150/jca.18893 This issue

Research Paper

HOXC6 Overexpression Is Associated With Ki-67 Expression and Poor Survival in NPC Patients

Shih-Lun Chang1, 2, Ti-Chun Chan3, Tzu-Ju Chen2, 4, Sung-Wei Lee5, Li-Ching Lin6, Khin Than Win4✉

1. Department of Otolaryngology, Chi Mei Medical Center, Yongkang District, Tainan City, Taiwan;
2. Department of Optometry, Chung Hwa University of Medical Technology, Tainan, Taiwan;
3. Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan;
4. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan;
5. Department of Radiation Oncology, Chi Mei Medical Center, Liouying, Tainan, Taiwan;
6. Department of Radiation Oncology, Chi Mei Medical Center, Tainan, Taiwan.

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Chang SL, Chan TC, Chen TJ, Lee SW, Lin LC, Win KT. HOXC6 Overexpression Is Associated With Ki-67 Expression and Poor Survival in NPC Patients. J Cancer 2017; 8(9):1647-1654. doi:10.7150/jca.18893. Available from https://www.jcancer.org/v08p1647.htm

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BACKGROUND: Homeobox (HOX) genes are expressed in adult cells and regulate expression of genes involved in cell proliferation as well as cell-cell and cell-extracellular matrix interactions. Dysregulation of HOX gene expression plays important roles in carcinogenesis in a variety of organs. Through data mining on a published transcriptome dataset, this study first identified Homeobox protein Hox-C6 (HOXC6) gene as one of the differentially upregulated genes in nasopharyngeal carcinoma (NPC). We aimed to evaluate HOXC6 expression and its prognostic effect in a large cohort of NPC patients.

METHODS: We retrospectively examined the HOXC6 expression and Ki-67 index by immunohistochemistry in biopsy specimens from 124 patients with non-metastasized NPC. The results were correlated with the clinicopathological variables including disease-specific survival (DSS), metastasis-free survival (MeFS), and local recurrence-free survival (LRFS).

RESULTS: HOXC6 high expression was positively correlated with increased Ki-67 labeling index, and significantly associated with increment of tumor stage (p=0.024), advanced nodal status (p<0.001) and American Joint Committee on Cancer (AJCC) stage (p=0.002). Its expression also correlated with worse prognosis in terms of DSS (p=0.008), MeFS (p=0.0047) univariately. In multivariate analyses, HOXC6 expression still remained prognostically independent to portend worse DSS (p=0.015, hazard ratio=1.988) and MeFS (p=0.036, hazard ratio=1.899), together with stage III-IV (p=0.024, DSS; p=0.043, MeFS).

CONCLUSION: In summary, our results suggest HOXC6 may play a critical role in NPC progression and may serve as a potential prognostic biomarker in NPC patients.

Keywords: HOXC6, nasopharyngeal carcinoma, Prognosis.