Chemokine Receptors 6 and 7 Identify a Metastatic Expression Pattern in Squamous Cell Carcinoma of the Head and Neck

Author(s):  
Jun Wang ◽  
Liqiang Xi ◽  
William Gooding ◽  
Tony E. Godfrey ◽  
Robert L. Ferris
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiang Wu ◽  
Jin Li ◽  
Tingyuan Yan ◽  
Xueping Ke ◽  
Xin Li ◽  
...  

Abstract Background The homeobox gene Homeobox B7 (HOXB7) is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, migration and invasion. However, its expression pattern and oncogenic role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we aimed to explore the expression pattern of HOXB7, its clinical significance as well as functional roles in HNSCC. Methods HOXB7 mRNA expression in HNSCC was determined by data mining and analyses from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The protein abundance of HOXB7 was measured by immunohistochemistry in 119 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The pro-tumorigenic roles of HOXB7 in HNSCC were further delineated in vitro by loss-of-function assay. And a xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for HOXB7. Results Bioinformatics analyses showed that HOXB7 mRNA was significantly overexpressed in 8 independent HNSCC datasets from TCGA and GEO databases. HOXB7 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with high pathological grade, advanced clinical stage, cervical node metastasis (P = 0.0195, 0.0152, 0.0300) and reduced overall and disease-free survival (P = 0.0014, 0.0007). Univariate and multivariate Cox regression analyses further revealed HOXB7 as an independent prognostic factor for patients’ overall survival. Moreover, HOXB7 knockdown significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in HNSCC cells, and resulted in compromised tumour growth in vivo. Furthermore, CMap (Connectivity map) analysis has identified three potential bioactive small molecule inhibitors (NU-1025, thiamine, vinburnine) for HOXB7 targeted therapy in HNSCC. Conclusions Our findings revealed that overexpression of HOXB7 was associates with tumour aggressiveness and unfavourable prognosis by serving a novel prognostic biomarker in HNSCC. Moreover, HOXB7 might be involved in the development and progression of HNSCC as an oncogene, and thereby might be a potential therapeutic target for HNSCC.


2015 ◽  
Vol 8 (4) ◽  
pp. 287-295 ◽  
Author(s):  
Eleni M. Rettig ◽  
Christine H. Chung ◽  
Justin A. Bishop ◽  
Jason D. Howard ◽  
Rajni Sharma ◽  
...  

2003 ◽  
Vol 123 (8) ◽  
pp. 950-953 ◽  
Author(s):  
Boban M. Erovic ◽  
Martina Pelzmann ◽  
Dritan Turhani ◽  
Johannes Pammer ◽  
Verena Niederberger ◽  
...  

2004 ◽  
Vol 64 (5) ◽  
pp. 1861-1866 ◽  
Author(s):  
Jun Wang ◽  
Liqiang Xi ◽  
Jennifer L. Hunt ◽  
William Gooding ◽  
Theresa L. Whiteside ◽  
...  

Oral Oncology ◽  
2016 ◽  
Vol 56 ◽  
pp. 8-16 ◽  
Author(s):  
Janine Mayra da Silva ◽  
Danilo Figueiredo Soave ◽  
Tálita Pollyanna Moreira dos Santos ◽  
Aline Carvalho Batista ◽  
Remo Castro Russo ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15527-15527
Author(s):  
M. H. Federico ◽  
C. M. Campofiorito ◽  
F. R. Mangone ◽  
S. Maistro ◽  
F. S. Pasini ◽  
...  

15527 Background and Methods: Chemokine receptors seem to be involved in tumor spread to lymph nodes and influence outcome in cancer patients (pts). Here, we have determined the mRNA expression of CCR7, CX3CR1 and CXCR1 chemokines, by means of Ribonuclease Protection Assay, in 60 fragments of primary tumor and matched adjacent mucosa of pts with head and neck squamous cells carcinoma (HNSCC) submitted to curative surgery. For Kaplan Meier survival curves, pts were categorized for each chemokine as positive or negative if above or equal/below median densitometric value of the entire tumor group. Results: In the whole study population, CCR7 status did not impact on overall survival (OS) (P=0.118, Log Rank) and on disease free survival (DFS) (P = 0.102), neither. When the subgroup of oral SCC was considered (n = 19), the CCR7 negative pts (n = 10) presented a longer DFS and OS (median DFS and OS not reached) as compared to CCR7 positive pts (n = 9) (mDFS: 4.9 months, P = 0.001 and mOS 10.47 months P = 0.003). In the HNSCC group as a whole, the CX3CR1 negative pts presented a trend toward longer OS (mOS 26.60 months in negative group, n = 25 vs 15.43 months in the positive group, n = 35, P = 0.073) and a longer DFS (mDFS not reached in CX3CR1 negative vs 9.20 months in positive pts, P = 0.041). In the oral SCC subgroup, CX3CR1 negative pts (n = 8) presented significantly better DFS (mDFS not reached) as compared to CX3CR1 positive pts (n = 11, mDFS 4.9 months, P = 0.004). OS was also superior for oral SCC CX3CR1 negative (mOS not reached) as compared to positive pts (mOS 10.47 months, P = 0.008). Taking into account larynx SCC, mDFS and mOS were not reached for CX3CR1 negative pts (n = 5) as compared to positive pts (n = 11, mDFS 8.57 months, P = 0.016; mOS 12.37 months, P = 0.041). In larynx subgroup, the other receptor associated to an advantage in terms of both DFS and OS was the negativity for CXCR1 (mDFS not reached for negative vs 8.47 months for positive pts, P = 0.006; mOS not reached for negative vs 8.47 months for positive pts, P = 0.025). Conclusions: Even if the mechanisms are not clear, our data suggest that low expression of CCR7, CX3CR1 and CXCR1 mRNA may be markers of better outcome in Head and Neck Squamous Cell Carcinoma. Further studies are warranted to confirm these results. No significant financial relationships to disclose.


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