Prognostic significance of VEGF-C, semaphorin 3F, and neuropilin-2 expression in oral squamous cell carcinomas and their relationship with lymphangiogenesis

Abstract Background To investigate the expression of transcription factor Dickkopf-1 (DKK1) in oral squamous cell carcinomas (OSCC) by bioinformatics analysis and to clarify the connection between expression of DKK1 and clinicopathological features of OSCC, so as to elucidate the early diagnosis and prognostic significance of OSCC by DKK1. Methods This study used the GEPIA database in conjunction with the TCGA database to analyze the expression level of DKK1 in OSCC tissues and then verify it by QRTPCR and Western-blot analysis in vitro. The LinkedOmics database was used to describe the correlation between DKK1 expression and clinical pathological parameters of OSCC and its impact on prognosis. DKK1 was knocked down by RNA interference approach in SCC-4 and SCC-25 OSCC cell lines. In addition, the proliferation ability was assessed by MTT assay. Results DKK1 was highly expressed in OSCC and positively correlated with OSCC pathological grade and T stage. The results of TCGA showed that high DKK1 mRNA expression was associated with overall survival in OSCC. Besides, both DKK1 mRNA and protein expression was confirmed increased significantly in oral squamous cell carcinomas SCC-25 and SCC-4. Furthermore, MTT analysis investigated that knockdown of DKK1 caused reduced proliferation ability of OSCC cells. Conclusions The TCGA database analysis found that DKK1 is highly expressed in OSCC and is associated with multiple pathological indicators of OSCC, which will provide important theoretical guidance for subsequent oral squamous cell carcinoma research.

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Prognostic significance of CD44v6, p63, podoplanin and MMP-9 in oral squamous cell carcinomas

Oral Diseases ◽

10.1111/odi.12442 ◽

2016 ◽

Vol 22 (4) ◽

pp. 303-312 ◽

Cited By ~ 21

Author(s):

LS Monteiro ◽

ML Delgado ◽

S Ricardo ◽

B do Amaral ◽

F Salazar ◽

...

Keyword(s):

Squamous Cell ◽

Prognostic Significance ◽

Squamous Cell Carcinomas ◽

Oral Squamous Cell Carcinomas

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Prognostic significance of cyclin D1 amplification and overexpression in oral squamous cell carcinomas

Oral Oncology ◽

10.1016/s1368-8375(03)00048-4 ◽

2003 ◽

Vol 39 (6) ◽

pp. 610-618 ◽

Cited By ~ 65

Author(s):

Ryozo Miyamoto ◽

Narikazu Uzawa ◽

Shunya Nagaoka ◽

Yasushi Hirata ◽

Teruo Amagasa

Keyword(s):

Cyclin D1 ◽

Squamous Cell ◽

Prognostic Significance ◽

Squamous Cell Carcinomas ◽

Oral Squamous Cell Carcinomas

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EMMPRIN Expression in Oral Squamous Cell Carcinomas: Correlation with Tumor Proliferation and Patient Survival

BioMed Research International ◽

10.1155/2014/905680 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 21

Author(s):

Luís Silva Monteiro ◽

Maria Leonor Delgado ◽

Sara Ricardo ◽

Fernanda Garcez ◽

Barbas do Amaral ◽

...

Keyword(s):

Squamous Cell ◽

Prognostic Significance ◽

Squamous Cell Carcinomas ◽

Membrane Expression ◽

Cancer Specific Survival ◽

Ki 67 ◽

Oral Squamous Cell Carcinomas ◽

Poorly Differentiated ◽

Well Differentiated ◽

Tumor Expression

The aim of our study was to explore the clinicopathological and prognostic significance of extracellular matrix metalloproteinase inducer (EMMPRIN) expression in oral squamous cell carcinomas (OSCC), and its relation with the proliferative tumor status of OSCC. We examined EMMPRIN and Ki-67 proteins expression by immunohistochemistry in 74 cases with OSCC. Statistical analysis was conducted to examine their clinicopathological and prognostic significance in OSCC. EMMPRIN membrane expression was observed in all cases, with both membrane and cytoplasmic tumor expression in 61 cases (82.4%). EMMPRIN overexpression was observed in 56 cases (75.7%). Moderately or poorly differentiated tumors showed EMMPRIN overexpression more frequently than well-differentiated tumors(P=0.002). Overexpression of EMMPRIN was correlated with high Ki-67 expression(P=0.004). In the multivariate analysis, EMMPRIN overexpression reveals an adverse independent prognostic value for cancer-specific survival (CSS)(P=0.034). Our results reveal that EMMPRIN protein is overexpressed in more than two-thirds of OSCC cases, especially in high proliferative and less differentiated tumors. The independent value of EMMPRIN overexpression in CSS suggests that this protein could be used as an important biological prognostic marker for patients with OSCC. Moreover, the high expression of EMMPRIN makes it a possible therapeutic target in OSCC patients.

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Prognostic Significance of Glycolytic Metabolic Change Related to HIF-1α in Oral Squamous Cell Carcinomas

The Korean Journal of Pathology ◽

10.4132/koreanjpathol.2010.44.4.360 ◽

2010 ◽

Vol 44 (4) ◽

pp. 360 ◽

Cited By ~ 1

Author(s):

Sook Hee Hong ◽

Sang Young Roh ◽

Yoon Ho Ko ◽

Hye Sung Won ◽

Myung Ah Lee ◽

...

Keyword(s):

Squamous Cell ◽

Prognostic Significance ◽

Squamous Cell Carcinomas ◽

Metabolic Change ◽

Oral Squamous Cell Carcinomas

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Prognostic Significance of Cyclins A2, B1, D1, and E1 and CCND1 Numerical Aberrations in Oral Squamous Cell Carcinomas

Analytical Cellular Pathology ◽

10.1155/2018/7253510 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Luís Silva Monteiro ◽

Márcio Diniz-Freitas ◽

Saman Warnakulasuriya ◽

Tomás Garcia-Caballero ◽

Jerónimo Forteza-Vila ◽

...

Keyword(s):

Cyclin D1 ◽

Squamous Cell ◽

Prognostic Significance ◽

Cyclin B1 ◽

Squamous Cell Carcinomas ◽

High Expression ◽

Hybridization Technique ◽

Oral Squamous Cell Carcinomas ◽

Numerical Aberrations ◽

Cyclin A2

We analysed the expression of cyclins A2, B1, D1, and E1 by immunohistochemistry and numerical aberrations in CCND1 gene by fluorescence in situ hybridization technique in 67 primary oral squamous cell carcinomas (OSCC). Cyclin A2 expression was observed in 54 (83.1%) tumours, cyclin D1 in 58 (89.2%), cyclin B1 in 39 (60%), and cyclin E in 21 (32.8%). CCND1 region analysis revealed 26 (43.3%) tumours with the presence of numerical aberrations which were correlated with cyclin D1 high expression (Rho = 0.48; p<0.001). Twenty-nine (45.3%) tumours were classified as high proliferative tumours assessed by Ki-67 protein expression and correlated with tumours with high expression of cyclin A2 (Rho = 0.30; p=0.016) and cyclin B1 (Rho = 0.37; p=0.003). In multivariate analysis for an overall five-year survival (OS), we found an adverse independent prognostic value for cyclin A2 high expression (p=0.031) and for advanced tumour stage (p<0.001). Our results confirm that several cyclins are commonly expressed in OSCC. CCND1 gene is abnormal in more than one-third of the cases and is frequently associated with cyclin D1 high expression. Moreover, cyclin A2 high expression is an independent indicator of worse OS suggesting that this protein may serve as a reliable biological marker to identify high-risk subgroups with poor prognosis.

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