Molecular classification of oral cancer by cDNA microarrays identifies overexpressed genes correlated with nodal metastasis

Warner, Giles; Reis, Patrícia P.; Jurišica, Igor; Sultan, Mujahid; Arora, Shilpi; MacMillan, Christina; Mäkitie, Antti; Grénman, Reidar; Reid, N.; Sukhai, Mahadeo A.; Freeman, Jeremy L.; Gullane, Patrick; Irish, Jonathan C.; Kamel‐Reid, Suzanne

doi:10.1002/ijc.20197

Cited by 60 publications

(46 citation statements)

References 49 publications

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“…HNSCC may be a useful system for studying lymphatic metastasis because of the high probability of lymphatic spread and low probability of hematogenous spread. A recent study has identified a gene signature for recurrent disease in HNSCC and several studies have investigated the changes in gene expression from normal tissue to carcinoma, but studies involving lymphatic metastasis have been limited by the small number of genes assessed and/or lack of a rigorous efficacy test of the metastatic signature (Alevizos et al, 2001;Belbin et al, 2002;Mendez et al, 2002;Hwang et al, 2003;Gonzalez et al, 2003;Leethanakul et al, 2003;Nagata et al, 2003;Chung et al, 2004;Ginos et al, 2004;Schmalbach et al, 2004;Warner et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

et al. 2004

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Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was built using a support vector machine, and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible.

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Section: Introductionmentioning

confidence: 99%

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

et al. 2004

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“…3 CLDN1, expressed in epithelial and endothelial cells, 4 is an integral component of tight junctions and functions in controlling cell-cell adhesion. 5 Claudins, comprised thus far of 24 isoforms, 6 are 20-to 27-kDa tight junction-associated transmembrane proteins.…”

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confidence: 99%

Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma

Reis

Bharadwaj

Machado

et al. 2008

Cancer

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104

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BACKGROUND.The authors have previously shown that overexpression of claudin 1 (CLDN1) is associated with advanced disease stage in oral squamous cell carcinomas (OSCCs). Their goal was to examine CLDN1 expression in a large series of primary OSCCs and to further investigate whether CLDN1 overexpression plays a role in invasion in OSCC.METHODS.CLDN1 gene expression levels were determined by quantitative real‐time reverse transcription polymerase chain reaction (QRT‐PCR) in 100 primary OSCCs. CLDN1 protein expression was examined by immunohistochemistry in 70 of 100 OSCCs. E‐Cadherin protein levels were also assessed in 58 OSCCs. The authors performed a transwell Matrigel invasion assay for assessment of the invasive potential of CLDN1 overexpressing oral carcinoma cells. Western blotting and QRT‐PCR were used to assess CLDN1 expression in transfected cells and controls.RESULTS.CLDN1 mRNA was increased (median = 18.5) in 79 of 100 OSCCs, compared with normal oral mucosa (expression = 1.0). CLDN1 overexpression was associated with angiolymphatic (P = .037) and perineural invasion (P = .051). CLDN1 was highly expressed in 48 of 70 (68%) OSCCs. E‐Cadherin was lost or underexpressed in 49 of 58 (84%) OSCCs. The invasion assay showed that cells overexpressing CLDN1 have increased invasive potential, whereas small interfering RNA–mediated depletion of CLDN1 decreased the invasive potential of cells.CONCLUSIONS.CLDN1 overexpression is associated with angiolymphatic and perineural invasion, consistent with aggressive tumor behavior. Overexpression of CLDN1 protein is associated with increased invasiveness of oral carcinoma cells. Cancer 2008. © 2008 American Cancer Society.

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“…pp-GalNAc-T1, T2, T3 and T6 are expressed in oral cell carcinoma [45][46][47][48]. They Oglycosylate fibronectin forming glycosylated onco-foetal fibronectin (GOF) in the stroma of malignant cells [49].…”

Section: Role In Cancermentioning

confidence: 99%

UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase- 6 (pp-GalNAc-T6): Role in Cancer and Prospects as a Drug Target

Banford¹,

Timson

2016

CCDT

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UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-6 (pp-GalNAc-T6) is a member of the N-acetyl-D-galactosamine transferase family. It catalyzes the addition of N-acetyl-D-galactosamine to proteins, often the first step in Oglycosylation of proteins. Glycosylated proteins play important roles in vivo in the cell membrane. These are often involved in cell-cell adhesion, cytoskeleton regulation and immune recognition. pp-GalNAc-T6 has been shown to be upregulated in a number of types of cancer. Abnormally glycosylated forms of mucin 1 (substrate of the enzyme), are used clinically as a biomarker for breast cancer. There is potential for other products of the pp-GalNAc-T6 catalyzed reaction to be used. It is also possible that pp-GalNAc-T6 itself could be used as a biomarker, since levels of this protein tend to be low in nonmalignant tissues. pp-GalNAc-T6 has been implicated in malignant transformation and metastasis of cancer cells. As such, it has considerable potential as a target for chemotherapy. To date, no selective inhibitors of the enzyme have been identified. However, general inhibitors of the enzyme family result in reduced cell surface Olinked glycosylation and induce apoptosis in cultured cells. Thus, a selective inhibitor of pp-GalNAc-T6 is likely to target cancer cells and could be developed into a novel anticancer therapy.

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Molecular classification of oral cancer by cDNA microarrays identifies overexpressed genes correlated with nodal metastasis

Cited by 60 publications

References 49 publications

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

Claudin 1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma

UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase- 6 (pp-GalNAc-T6): Role in Cancer and Prospects as a Drug Target

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