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

Abstract

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.

HOXC6 gene silencing inhibits epithelial-mesenchymal transition and cell viability through the TGF-β/smad signaling pathway in cervical carcinoma cells

“…A previous study highlighted overexpression f HOXC6 in tumor tissues of colorectal cancer [26]. It has been reported that there are correlations of HOXC6 overexpression with increment of tumor stage, advanced nodal status in nasopharyngeal carcinoma [27].…”

<p>Overexpression of HOXC6 promotes cell proliferation and migration via MAPK signaling and predicts a poor prognosis in glioblastoma</p>

“…Numerous studies have reported that HOXC6, as a member of the HOX gene family, was overexpressed in various cancers, and played a key role in promoting cancer progression, suggesting that HOXC6 was a potential biomarker for diagnostic, prognostic and therapeutic target of cancers 16–18. For instance, Chen et al found that HOXC6 gene significantly promoted the proliferation, invasion and metastasis of gastric cancer cells by upregulation of MMP9, which was associated with the poor prognosis of gastric cancer patients 19.…”

Prognostic and clinicopathological value of Ki-67 expression in patients with nasopharyngeal carcinoma: a meta-analysis

“…The pooled data were as follows: HR = 2.86, 95% CI = 1.91–4.27, p < 0.001, indicating that high Ki-67 expression predicted poor OS. Similarly, the combined HRs and 95% CIs from six studies, 16 – 19 , 22 , 23 and three studies, 18 , 19 , 23 showed that Ki-67 overexpression was also correlated with worse PFS (HR = 1.78, 95% CI = 1.15–2.74, p = 0.009; I 2 = 52%, p = 0.064) and unfavorable DMFS (HR = 1.65, 95% CI = 1.15–2.36, p = 0.007; I 2 = 23.4%, p = 0.271) ( Figure 2 , Table 2 ). However, no significant correlation was found between high Ki-67 expression and LRFS (HR = 1.07, 95% CI = 0.54–2.14, p = 0.843; I 2 = 52.1%, p = 0.124) based on the data of three studies.…”