title: Zinc finger A20 and NF-κB correlate with high-risk human papillomavirus of squamous cell carcinoma patients.
abstract: Genital human papillomavirus (HPV) is associated with the development of cutaneous malignant tumors, and differences in HPV subtypes are found in several cancers by histology. NF-κB is persistently activated in most cancers and confers a survival advantage to cancer cells, while A20 is a critical negative regulator of NF-κB and is an important tumor suppressor inactivated in B cell lymphomas. This study was undertaken to identify HPV types in cutaneous squamous cell carcinoma (SCC) as well as to determine whether the crosstalk of A20/NF-κB was involved in HPV-induced SCC. Overall, HPV positivity was observed to be 66.2 %, with HPV16 being most common followed by infection with HPV18. Out of 43 HPV-positive samples, 35 samples were positive for one or more high-risk HPV (HR-HPV) types, suggesting a high association of SCC with HR-HPV infection, while only five HPV infections were detected in 21 normal skin samples and low-risk HPV (LR-HPV) infection was the most common. Both A20 and NF-κB were overexpressed in HPV-positive SCC samples (56 vs 87.4 %) and were closely correlated with TNM stage and lymph node transfer, respectively. More interestingly, the expression of A20 and NF-κB was much higher in HR-HPV samples than in LR-HPV samples. These results suggest that the crosstalk of A20 and NF-κB may contribute to HR-HPV-associated tumor growth and metastasis of SCC and may be a novel therapeutic target for SCC in the future.
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital of Suzhou University, 185 Juqian Street, Changzhou, Jiangsu, People's Republic of China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Tang
authors.forename: Ahmad Taha
authors.initials: AT
authors.lastname: Khalaf
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Chun-Xing
authors.initials: CX
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Sai
authors.initials: S
authors.lastname: Cheng
authors.forename: Ru-Zhi
authors.initials: RZ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D016328:NF-kappa B / Q000378:metabolism*; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3