A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

Ries, Jutta; Mollaoğlu, Nur; Toyoshima, Takeshi; Vairaktaris, Eleftherios; Neukam, Friedrich Wilhelm; Ponader, Sabine; Nkenke, Emeka

doi:10.1155/2009/510124

Cited by 17 publications

(15 citation statements)

References 28 publications

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“…In the literature, correlations among binary markers are often not described directly but may be inferred. For example, Ries et al examined 12 MAGE-A antigens for oral squamous cell carcinoma (OSSC) 8. They reported that singly, six of these markers were positive at rates between 40% and 55% for OSSC; each was negative in all control subjects.…”

Section: Discussionmentioning

confidence: 99%

Building Multi-Marker Algorithms for Disease Prediction–-The Role of Correlations among Markers

Pinsky

Zhu

2011

Biomark�Insights

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A widely held viewpoint in the field of predictive biomarkers for disease holds that no single marker can provide high enough discrimination and that a panel of markers, combined in some type of algorithm, will be needed. Motivated by a recent study where 27 additional markers for ovarian cancer, many of which had good predictive value alone, failed to substantially increase the predictive ability of the primary marker of CA125, we explore the effect of additional markers on the area under the ROC curve (AUC). We develop a statistical model based on the multivariate normal distribution and linear algorithms and use it to explore how the magnitude and direction of statistical correlation among the markers (in diseased and in non-diseased) is critical in determining the added predictive value of additional markers. We show mathematically and empirically that if the additional marker(s) is negatively correlated with the primary marker, then it will always be able to provide increased AUC when combined with the primary marker (as compared to that obtained with the primary marker alone), even if it has little predictive ability on its own. In contrast, if the additional marker(s) is positively correlated with the primary marker, then it is unlikely to substantially increase the AUC when combined with the primary marker, even when it has good predictive ability on its own. Thus, univariate analyses alone may not be the best approach in choosing which markers to combine in a predictive panel of markers; patterns of statistical correlation should be considered in ranking top-performing biomarkers.

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Section: Discussionmentioning

confidence: 99%

Building Multi-Marker Algorithms for Disease Prediction–-The Role of Correlations among Markers

Pinsky

Zhu

2011

Biomark�Insights

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“…Besides the tissue analysis of suspected lesions, the molecular diagnosis of early oral cancer has recently developed. Expression of MAGE-A was restricted to OCSCC and was considered to be used in the early detection of oral cancer [144]. The epithelial tumor markers Cyfra 21-1, TPS and CA12, various oxidative stress-related salivary parameters, such as reactive oxygen species and reactive nitrogen species, biochemical and immunological para meters, such as IGF, MMPs and RNA transcripts of IL8, IL-1B, DUSP1, HA3, OAZ1, S100P and SAT were altered significantly in the saliva, an observation that is potentially useful in the early detection of oral cancer in the future [145].…”

Section: Current Molecular Markers Applied To Early Diagnosis Of Ocsccmentioning

confidence: 99%

Clinical, Pathological and Molecular Determinants in Squamous Cell Carcinoma of the Oral Cavity

et al. 2010

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Squamous cell carcinoma of the oral cavity (OCSCC) is the most frequently observed form of head-and-neck cancer in Southeast Asia and is the sixth most common cancer worldwide. Most cases of this preventable disease are caused by alcohol consumption, smoking and betel nut chewing. The survival rates of patients with advanced OCSCC have not increased significantly in recent years. While treatments for OCSCC are similar worldwide, survival rates differ by geographical area. The various genetic profiles and individual genetic susceptibility for carcinogens may account for this discrepancy. In some respects, molecular alteration or accumulation affects tumor progression and the clinical outcomes among patients with OCSCC. Clarifying the tumor behavior of oral cancer, with regard to pathological features or molecular aspects, could help clinicians to judge, tailor and adopt more effective therapeutic strategies to treat oral cancer.

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“…Expression of human melanoma‐associated antigen ( MAGE ) family genes has been recently associated with several types of cancer 3–7. The first human MAGE family member was discovered as a gene encoding a tumor‐specific antigen 8.…”

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MAGE‐D4B is a novel marker of poor prognosis and potential therapeutic target involved in breast cancer tumorigenesis

Germano¹,

Kennedy²,

Rani³

et al. 2011

Intl Journal of Cancer

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Melanoma-associated antigen (MAGE) family members are generally described as tumor-specific antigens. An association between MAGE-D4B and breast cancer has yet to be reported and the functional role of the encoded protein has never been established. We performed microarray analysis of 104 invasive breast tumors and matched non-cancerous breast biopsies. qPCR was used for validation in an independent biobank. To investigate the biological relevance of MAGE-D4B in breast tumorigenesis, its phenotypic effects were assessed in vitro. Overall, MAGE-D4B was detected in 43% of tumors while undetected in normal breast tissue. MAGE-D4B was found to correlate with tumor progression and to be an independent prognostic marker for poor outcome in term of relapse-free and overall survival, with potential predictive relevance in relation to response to chemotherapy. RNA interference-mediated knockdown of MAGE-D4B significantly hampered the invasive properties of Hs578T cells by affecting anchorage-independent growth, adhesion, migration and invasion affecting anchorageindependent growth, adhesion, migration and invasion and by modulating expression of invasion-suppressor gene E-cadherin.Breast cancer is the most common cancer in women and one of the leading causes of death 1 and it is characterized by high heterogeneity at the histopathologic and molecular levels, which is ultimately reflected in the clinical course of the disease and responses to treatment. The prognosis and clinical management of patients with breast cancer are commonly determined by clinicopathological factors and immunochemical markers. Histological type, grade, tumor size, lymph node involvement, estrogen (ER) and progesterone (PR) receptors status and HER2-receptor overexpression/gene amplification all influence prognosis and probability of response to systemic therapies; however, they fail to fully capture the varied clinical course of breast cancer. 2 Expression of human melanoma-associated antigen (MAGE) family genes has been recently associated with several types of cancer. [3][4][5][6][7] The first human MAGE family member was discovered as a gene encoding a tumor-specific antigen. 8 Since then, more than 50 MAGE genes have been identified and classified as type I and type II genes, based on differences in gene structure and tissue-specific gene expression. 9 Type II MAGE-D genes are characterized by a more complex genomic structure compared to type I genes, with an open reading frame encoded by multiple exons. 10 One of these genes, MAGE-D4B, has been reported in human malignancies, including gliomas, non-small-cell lung cancers and oral squamous cell carcinomas. [11][12][13] However, an association of MAGE-D4B expression with breast cancer has not previously been established and the functional role of the encoded protein remains uncharacterized.In this study, by genome-wide microarray analysis of a large cohort of patients, we identified MAGE-D4B to be differentially expressed in invasive breast tumors compared with normal breast tissue and to be ...

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A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

Cited by 17 publications

References 28 publications

Building Multi-Marker Algorithms for Disease Prediction–-The Role of Correlations among Markers

Building Multi-Marker Algorithms for Disease Prediction–-The Role of Correlations among Markers

Clinical, Pathological and Molecular Determinants in Squamous Cell Carcinoma of the Oral Cavity

MAGE‐D4B is a novel marker of poor prognosis and potential therapeutic target involved in breast cancer tumorigenesis

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