The clinicopathological significances and biological functions of parafibromin expression in head and neck squamous cell carcinomas

Abstract

Downregulated parafibromin expression is involved in the pathogenesis and progression of parathyroid, breast, gastric, colorectal, and lung cancers. To investigate the roles of parafibromin expression in tumorigenesis, progression, and prognostic evaluation of head and neck squamous cell carcinomas (HNSCCs), we transfected parafibromin-expressing plasmid into HNSCC cell and examined the phenotypes and their relevant molecules. Parafibromin expression was detected on tissue microarray containing squamous epithelium, dysplasia, and carcinoma of head and neck by immunohistochemistry. Parafibromin overexpression was found to suppress growth, migration, and invasion, and induce apoptosis, S arrest, and mesenchymal to epithelial transition (EMT), compared with the mock and control (P < 0.05). Both overexpression of Cyclin E1, Bax, and E-cadherin and hypoexpression of c-myc, Bcl-xL, and slug were detected in B88 transfectants, in comparison to mock and control by real-time PCR. Parafibromin expression was weaker in primary cancers than those in normal squamous tissue and dysplasia (P < 0.05), but stronger than the metastatic cancers in lymph node (P < 0.05). Parafibromin expression was negatively correlated with lymph node metastasis, tumor-node-metastasis (TNM) staging, but positively with human papillomavirus (HPV) positivity (P < 0.05). The HNSCCs in tongue showed more parafibromin expression than those in larynx (P < 0.05). There was stronger parafibromin expression in moderately-than poorly-differentiated carcinomas (P < 0.05). The significantly positive correlation was observed between parafibromin expression and relapse-free survival rate by Kaplan-Meier curves (P < 0.05). Cox's proportional hazard model indicated that distant metastasis and parafibromin expression were independent prognostic factors for overall and relapse-free survival of HNSCC, respectively (P < 0.05). These findings suggest that downregulated expression of parafibromin protein plays an important role in the pathogenesis, differentiation, and metastasis of HNSCCs possibly by inducing apoptosis, suppressing proliferation, cell cycle progression, migration, invasion, and EMT. Parafibromin expression is an independent factor for relapse-free survival of HNSCCs.

Thein vitroandin vivoeffects of nuclear and cytosolic parafibromin expression on the aggressive phenotypes of colorectal cancer cells: a search of potential gene therapy target

“…Ile60Asn mutant overexpression led to increased cell proliferation and accumulation in G 2 /M-phase cells [13]. A body of evidences demonstrated that the down-regulated parafibromin expression was positively correlated with the tumorigenesis, aggressive parameters or worse prognoses of parathyroid [14], gastric [15], colorectal [16], breast [17], lung [18], ovarian [7], urothelial [19], head and neck [20] cancers. Previously, we observed parafibromin positivity in the cilia of the fallopian tube [7] and bronchial pseudo-stratified columnar epithelium [18].…”

Significance of Parafibromin Expression in Laryngeal Squamous Cell Carcinomas

“…However, the clinical significance and potential function of parafibromin expression in HNSCC have remained largely unknown. One study by Zhang et al [ 5 ] investigated the role of parafibromin expression in tumorigenesis and the progression of HNSCC, along with its value as a prognostic marker. The overall 5-year survival rate of HNSCC is about 40%–50%, despite advancements in therapy [ 5 ].…”

“…One study by Zhang et al [ 5 ] investigated the role of parafibromin expression in tumorigenesis and the progression of HNSCC, along with its value as a prognostic marker. The overall 5-year survival rate of HNSCC is about 40%–50%, despite advancements in therapy [ 5 ]. The prognosis of laryngeal cancer varies considerably according to the anatomical site of origin.…”

“…The gene encodes a 2.7-kb transcript that is translated into a 60-kD, 531-amino acid parafibromin protein [ 7 , 8 ]. Along with its role as an oncosuppressor, parafibromin binds to RNA polymerase II as part of polymeraseassociated factor 1 (Paf1), causing repression of β-catenin–mediated transcription and transcriptional repression of c-myc [ 5 , 9 ]. Zhang et al [ 10 ] documented that the overexpression of parafibromin results in anti-proliferative properties through the inhibition of colony formation and cellular proliferation and induces cell cycle arrest in the G1 phase.…”

“…Selvarajan et al [ 13 ] showed inverse correlations between parafibromin expression and tumor size, pathologic stage, and lymphovascular invasion of breast carcinomas. Subsequent investigations have suggested that down-regulated parafibromin expression is involved in tumor pathogenesis, growth, invasion, and metastasis and might be a novel biomarker indicating a poor prognosis in gastric and colorectal carcinomas [ 14 , 15 ] Zhang et al [ 5 ] demonstrated that the down-regulated expression of parafibromin protein might have a negative impact on apoptosis and suppressing cell cycle progression, proliferation, migration, invasion, and the epithelial mesenchymal transition (EMT), suggesting its important role in the pathogenesis, differentiation, and metastasis of head and neck squamous cell carcinoma (HNSCC). Parafibromin has recently been shown to be expressed in squamous cell carcinoma of the head and neck [ 5 ].…”