Potential Involvement of MYC- and p53-Related Pathways in Tumorigenesis in Human Oral Squamous Cell Carcinoma Revealed by Proteomic Analysis

Koehn, Jadranka; Krapfenbauer, Kurt; Huber, Susanna; Stein, Elisabeth; Sutter, Walter; Watzinger, Franz; Erovic, Boban M.; Thurnher, Dietmar; Schindler, Thomas; Fountoulakis, Michael; Turhani, Dritan

doi:10.1021/pr800077a

Cited by 24 publications

(30 citation statements)

References 62 publications

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“…Also important was the observation that the genes coding for several proteins overexpressed in tumors (both MA and LA) have been mapped to 11q13 ( CFL1 , GSTP1 , SERPINH1 ) and 8q23-24 ( EEF1D , RPL8 ), which are chromosome segments frequently amplified in head and neck carcinomas and may be related to the progression of the disease [30], [31]. Only cofilin-1 [32]–[34] and glutathione S-transferase P (or GSTP1-1) [33], [35] have been previously described in OSCC; otherwise, few studies have been done on SERPINH1 , EEF1D and RPL8 expression in head and neck carcinomas or other neoplasms.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Approaches Identify Members of Cofilin Pathway Involved in Oral Tumorigenesis

et al. 2012

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The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the “more-aggressive” group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the “less-aggressive” group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas.

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Section: Discussionmentioning

confidence: 99%

Proteomic Approaches Identify Members of Cofilin Pathway Involved in Oral Tumorigenesis

et al. 2012

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“…In most recent proteomics studies done on HNSCC cell lines, tissues, saliva, and secretomes aiming at biomarker discovery for head and neck cancer, normal samples and precancerous tissue (when used) are usually defined by abnormal histology (31)(32)(33)(34)(35)(36)(37)(38)(39). To our knowledge, our study is the first to use detailed genetic characterizations to ascertain the selection of strictly normal and precancerous tissues.…”

Section: Discussionmentioning

confidence: 99%

Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas

Schaaij-Visser

Graveland

Gauci

et al. 2009

Clinical Cancer Research

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Purpose: The 5-year survival rates of head and neck squamous cell carcinomas (HNSCC) remain disappointing. HNSCCs develop in precursor fields of genetically altered cells that are often not completely resected when the tumor is excised, causing local relapse. These precursor fields are mostly recognized as dysplasia, but histologic grading cannot reliably predict malignant transformation. Our aim was to discover and validate protein biomarkers that can detect precursor fields and predict local relapse in HNSCC using immunostaining of surgical margins. Experimental Design: We compared paired and genetically characterized normal, precursor, and tumor tissues of eight patients by proteome analysis to identify differentially expressed proteins. The prognostic value of candidate protein biomarkers was evaluated by immunohistochemical analysis of 222 surgical margins of 46 HNSCC patients who developed local relapse or remained disease free. Significant associations were determined by Kaplan-Meier survival analysis and Cox-proportional hazards models. Results: Forty proteins showed significant differential expression (false discovery ratecorrected P < 0.05). Most discriminative markers suited for immunostaining were keratin 4 and cornulin. Low expression in the surgical margins of keratin 4 (hazard ratio, 3.8; P = 0.002), cornulin (hazard ratio, 2.7; P = 0.025), and their combination (hazard ratio, 8.8; P = 0.0005) showed a highly significant association with the development of local relapse. Dysplasia grading had no prognostic relevance. Conclusions: Immunohistochemical assessment of keratin 4 and cornulin expression in surgical margins of HNSCC patients outperforms histopathologic grading in predicting the risk for local relapse. These markers can be used to initiate more frequent and lifelong surveillance of patients at high risk of local relapse, and enable selection for adjuvant treatment or tertiary prevention trials. (Clin Cancer Res 2009;15(24):7666-75) Head and neck squamous cell carcinoma (HNSCC) develops in the mucosal linings of the upper aerodigestive tract and is the sixth most common cancer worldwide (1). The 5-year survival rates of HNSCC are approximately 60% (1) and have only moderately improved the last decades (2) mainly because 20% to 40% of all patients develop a local relapse in the same or adjacent anatomic region even when the surgical margins are histologically tumor free (3, 4). Clinically these relapses at the primary and adjacent anatomic sites are assigned as local recurrences when they develop within three years and at <2 cm distance of the primary tumor. Relapses not fulfilling these criteria are clinically classified as second primary tumors. Despite the difference in clinical assignment, many local relapses have in fact the same pathobiological origin (3-8).It has been well established that HNSCC is the result of a multistep process characterized by the accumulation of genetic and epigenetic alterations (9). Genetic analysis of surgical margins has shown that HNSCC frequent...

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“…Both Bmi-1 and c-myc are capable of immortalising certain cells in vitro and these factors converge on the same pathways as c-myc signalling can influence Bmi-1 activity and vice versa (Jacobs et al, 1999;Dimri et al, 2002;Gil et al, 2005;Guney et al, 2006). C-myc is also assumed to participate in oral carcinogenesis, and downregulation of c-myc mRNA has even been associated with poor prognosis (Vora et al, 2007;Koehn et al, 2008).…”

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confidence: 99%

Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue

et al. 2010

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Background: The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor c-myc affects cell proliferation and apoptosis, and Snail regulates epithelial–mesenchymal transition. The expression of these markers has been connected to prognosis in many cancer types. Methods: Bmi-1, c-myc, and Snail expressions were studied in our material consisting of 73 primarily T1N0M0 oral tongue carcinoma patients. We compared the immunoexpressions of Bmi1, c-myc, and Snail with clinical parameters including the degree of histological differentiation, tumour size, TNM classification, depth of invasion, and resection margins. In addition, survival analyses were performed, comparing disease-free survival time with the registered protein expression of the markers mentioned above. Results: A significant correlation between Bmi-1 protein expression and recurrence (log-rank test, P =0.005) was detected. Snail and c-myc expression did not correlate with prognosis. Snail expression correlated with histopathological grade (Fisher's exact test, P =0.007) and with the invasion depth of tumours ( χ 2 -test, P =0.037). Conclusion: Negative Bmi-1 immunoexpression might serve as a marker of poor prognosis in oral tongue carcinoma patients.

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Potential Involvement of MYC- and p53-Related Pathways in Tumorigenesis in Human Oral Squamous Cell Carcinoma Revealed by Proteomic Analysis

Cited by 24 publications

References 62 publications

Proteomic Approaches Identify Members of Cofilin Pathway Involved in Oral Tumorigenesis

Proteomic Approaches Identify Members of Cofilin Pathway Involved in Oral Tumorigenesis

Differential Proteomics Identifies Protein Biomarkers That Predict Local Relapse of Head and Neck Squamous Cell Carcinomas

Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue

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