Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by relative quantification with real-time polymerase chain reaction

Zhong, Lai‐ping; Zhao, Shifang; Chen, Guan-Fu; Ping, Fei-yun; Xu, Zefeng; Hu, Jianguo

doi:10.1016/j.archoralbio.2006.05.005

Cited by 16 publications

(11 citation statements)

References 17 publications

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“…Standing out were 28 different keratin proteins identified and quantified in our proteomics analysis, with the majority of these showing significant increases in abundance between the pre-malignant and malignant sample pools. Among the keratins, we selected keratin 19 for validation, given past descriptions of its increased expression in OSCC tissues[23], [24]. We also observed that catalase, recently described as a saliva protein whose abundance change distinguishes healthy individuals from those with malignant oral lesions[9], and the protein S100A7, recently described as a biomarker distinguishing healthy and malignant oral tissue biopsies[7], were both modestly increased in abundance between the pre-malignant and malignant sample pools in our proteomic catalogue.…”

Section: Resultsmentioning

confidence: 91%

Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions

et al. 2010

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BackgroundOral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need.Methodology/Principal FindingsTo discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p = 0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells.Conclusions/SignificanceSalivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early.

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Section: Resultsmentioning

confidence: 91%

Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions

et al. 2010

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“…Interestingly, 15 of the 27 candidates were previously reported to be cancer‐related genes. The genes linked to OSCC included keratin 19, lectin, galactoside‐binding, soluble, 1 and IFI16 . Furthermore, five of the 27 upregulated genes were also found to be IFI genes, including IFI6 , IFI35 , AIM2 , IFI16 and bone marrow stromal cell antigen‐2.…”

Section: Resultsmentioning

confidence: 99%

“…The genes linked to OSCC included keratin 19, lectin, galactoside-binding, soluble, 1 and IFI16. (19)(20)(21) Furthermore, five of the 27 upregulated genes were also found to be IFI genes, including IFI6, IFI35, AIM2, IFI16 and bone marrow stromal cell antigen-2. Among them, the AIM2 and IFI16 genes are located within the HIN-200 gene cluster on 1q23 and have been identified as a new family of innate immune DNA sensors for intracellular DNA called AIM2-like receptors.…”

Section: Resultsmentioning

confidence: 99%

Overexpression of the DNA sensor proteins, absent in melanoma 2 and interferon‐inducible 16, contributes to tumorigenesis of oral squamous cell carcinoma with p53 inactivation

et al. 2012

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The development of oral squamous cell carcinoma (OSCC) is a multistep process that requires the accumulation of genetic alterations. To identify genes responsible for OSCC development, we performed high-density single nucleotide polymorphism array analysis and genome-wide gene expression profiling on OSCC tumors. These analyses indicated that the absent in melanoma 2 (AIM2) gene and the interferon-inducible gene 16 (IFI16) mapped to the hematopoietic interferon-inducible nuclear proteins. The 200-amino-acid repeat gene cluster in the amplified region of chromosome 1q23 is overexpressed in OSCC. Both AIM2 and IFI16 are cytoplasmic double-stranded DNA sensors for innate immunity and act as tumor suppressors in several human cancers. Knockdown of AIM2 or IFI16 in OSCC cells results in the suppression of cell growth and apoptosis, accompanied by the downregulation of nuclear factor kappa-light-chain-enhancer of activated B cells activation. Because all OSCC cell lines have reduced p53 activity, wild-type p53 was introduced in p53-deficient OSCC cells. The expression of wild-type p53 suppressed cell growth and induced apoptosis via suppression of nuclear factor kappa-light-chain-enhancer of activated B cells activity. Finally, the co-expression of AIM2 and IFI16 significantly enhanced cell growth in p53-deficient cells; in contrast, the expression of AIM2 and/or IFI16 in cells bearing wild-type p53 suppressed cell growth. Moreover, AIM2 and IFI16 synergistically enhanced nuclear factor kappa-light-chain-enhancer of activated B cells signaling in p53-deficient cells. Thus, expression of AIM2 and IFI16 may have oncogenic activities in the OSCC cells that have inactivated the p53 system. (Cancer Sci 2012; 103: 782-790) O ral squamous cell carcinoma is commonly found in lowincome communities. This cancer mainly affects older men; 90% of cases are in men over 45 years old who have been exposed to risk factors including tobacco and/or alcohol (International Agency for Research on Cancer [IARC] 2004). OSCC is the sixth most common cancer worldwide and affects approximately 270 000 people each year.(1) The incidence and rate of mortality from OSCC are rising in several regions of Europe, Australia and Asia, including Japan. Despite recent progress in OSCC diagnosis and therapy, the 5-year survival rate has not improved in more than two decades. Oral carcinogenesis is a multifactorial cascade involving numerous genetic changes that affect the activity of oncogenes, tumor suppressor genes and other classes of diseaserelated genes. Chronic exposure to carcinogens, such as tobacco, causes genetic changes in the epithelial cells of the oral mucosa. The activation of the COX-2,epidermal growth factor receptor, (4) and cyclin D1 oncogenes and the inactivation of the p16 and p53 tumor suppressor genes have also been reported in OSCC.(5-7) In addition to tobacco smoke exposure, chronic alcohol use and chronic inflammation can both induce genetic alterations.(3) The causative agent of cervical cancer, HPV is also reportedly associa...

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“…In the process of aerodigestive SCC development, a series of transitional events occur. In high-grade squamous dysplasia, the expression of CK19 is increased and extends to all dysplastic cells in all layers of the squamous epithelium [19]. Previous studies of the conventional type of invasive SCC revealed that CK19 mRNA level and protein expression are elevated in the tumor cells [20].…”

Section: Discussionmentioning

confidence: 99%

Acantholytic Squamous Cell Carcinoma in Upper Aerodigestive Tract: Histopathology, Immunohistochemical Profile and Epithelial Mesenchymal Transition Phenotype Change

Jiang

Fowler

2012

Head and Neck Pathol

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Acantholytic squamous cell carcinoma is a rare variant of squamous cell carcinoma in the mucosa of upper aerodigestive tract. Histomorphologically, acantholytic squamous cell carcinoma may lose the typical features of conventional squamous cell carcinoma and mimic other epithelial or mesenchymal malignancies due to advanced acantholysis and dyskeratosis. Because of its rarity, information of prognosis, pathologic features and immunohistochemical profiles is limited. We have studied clinicopathologic features and immunohistochemical profiles of four acantholytic squamous cell carcinoma cases arising from upper aerodigestive tract. Clinical results indicate an aggressive biologic behavior. Morphologically, all tumors revealed significant acantholysis with separation of tumor cells and intratumoral spaces. The tumor cells were highly pleomorphic and growth patterns were variable. In immunohistochemical studies, all tumor cells revealed positive reactions for AE1/AE3 and p63 supporting a squamous epithelial origin. In contrast to conventional aerodigestive squamous cell carcinoma, acantholytic squamous cell carcinoma showed significant reductions of cytokeratin19, E-cadherin and concomitant up-regulation of vimentin expression. Both morphologic features and immunohistochemical profiles indicate that acantholytic squamous cell carcinoma has acquired an epithelial mesenchymal transition phenotype. However, in contrast to other solid malignant tumors, the epithelial mesenchymal transition phenotype change in acantholytic squamous cell carcinoma is not limited to the invasive front of the peripheral tumor but, rather, diffusely involves entire neoplastic lesion. In addition, because cytokeratin 19 staining is attenuated, this would be an insensitive marker for following up and/or in detecting disseminated tumor cells in cases of acantholytic squamous cell carcinoma in upper aerodigestive tract.

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Increased levels of CK19 mRNA in oral squamous cell carcinoma tissue detected by relative quantification with real-time polymerase chain reaction

Cited by 16 publications

References 17 publications

Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions

Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions

Overexpression of the DNA sensor proteins, absent in melanoma 2 and interferon‐inducible 16, contributes to tumorigenesis of oral squamous cell carcinoma with p53 inactivation

Acantholytic Squamous Cell Carcinoma in Upper Aerodigestive Tract: Histopathology, Immunohistochemical Profile and Epithelial Mesenchymal Transition Phenotype Change

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