Cyclin D1 overexpression and poor clinical outcomes in Taiwanese oral cavity squamous cell carcinoma

Abstract

BackgroundCyclin D1 gene regulates cell cycle and plays an important role in the tumorigenesis of human cancers. The association between cyclin D1, clinicopathologic parameters and prognosis in oral cavity squamous cell carcinoma (OSCC) is inconclusive.MethodsA total of 264 male OSCCs were examined for cyclin D1 protein expression using immunohistochemistry (IHC). The expression levels of cyclin D1 were defined as overexpression when more than 10% of tumor cells displayed nuclear staining with moderate to strong intensity.ResultsOverexpression of cyclin D1 was found in 97 (36.7%) OSCCs. Cyclin D1 protein overexpression was significantly associated with lymph node metastasis (P = 0.002), tumor cell differentiation (P = 0.031) and tumor stage (P = 0.051), but not associated with age onset, cigarette smoking, alcohol drinking, or areca quid chewing. Overexpression of cyclin D1 was also significantly associated with poor clinical outcomes in terms of disease-free survival (DFS, P = 0.002) and overall survival (OS, P < 0.001). The effects of cyclin D1 protein overexpression on DFS (hazard ratio (HR) = 1.540; 95% confidence interval (CI), 1.068 - 2.222) and OS (HR = 1.702; 95% CI, 1.168 - 2.480) were still existed after adjusting for clinicopathological paremeters (such as age, primary tumor status, tumor cell differentiation, and lymph node metastasis) using logistic multivariate analysis.ConclusionCyclin D1 protein worked as an independent prognostic factor and can be as a biomarker for the aggressiveness of OSCC.

QKI-5 suppresses cyclin D1 expression and proliferation of oral squamous cell carcinoma cells via MAPK signalling pathway

“…13 Previous clinical investigations have shown that OSCC survival is significantly influenced by the level of cyclin D1 expression, and over 30% of the studied OSCC tissue samples showed overexpression of cyclin D1 protein. [14][15][16] The high level of cyclin D1 mRNA may be because of enhanced transcription or mRNA stabilization. Transcription of cyclin D1 is controlled by several transcription factors, including STAT3/5A, nuclear factor kappa B (NFkB), ETS1, and AP1.…”

High interstitial fluid pressure promotes tumor cell proliferation and invasion in oral squamous cell carcinoma

“…Heat shock protein (HSP)A4, also known as HSP70, has been shown to be significantly associated with low differentiation and poor prognosis in a number of malignant tumors (17)(18)(19). CCND1, also known as cyclin D1, is overexpressed in several human tumors; its expression is induced by growth factors and occurs at multiple levels, including increased transcription, translation and protein stability (20)(21)(22). Cyclin D1 plays an important role in G1 phase transition, which is a kinase-independent function, by sequestering cyclin-dependent kinase (CDK) inhibitors, such as CDKN1A (p21) and CDKN1B (p27) for the efficient activation of CDK2-containing complexes (23,24).…”

Elevated Cyclin D1 Expression Is Predictive for a Benefit from TPF Induction Chemotherapy in Oral Squamous Cell Carcinoma Patients with Advanced Nodal Disease

“…Although increased expression of cyclin D1 in OSCC has been reported, there are controversial data on the prognostic value of cyclin D1 overexpression in OSCC. Some studies suggest that increased expression of cyclin D1 is associated with poor survival (12–16), while other studies demonstrate that cyclin D1 overexpression provides little prognostic information for patients with OSCC (17,18). …”