Gene expression signatures that can discriminate oral leukoplakia subtypes and squamous cell carcinoma

Kondoh, Nobuo; Ohkura, Shuri; Arai, Masaaki; Hada, Akiyuki; Ishikawa, Takahiro; Yamazaki, Yutaka; Shindoh, Masanobu; Takahashi, Masayuki; Kitagawa, Yoshimasa; Matsubara, Osamu; Yamamoto, Mikio

doi:10.1016/j.oraloncology.2006.04.012

Cited by 40 publications

(54 citation statements)

References 24 publications

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“…To further elucidate the wide variety of genetic events that occur during the development of OSCC from precancerous lesions (leukoplakias) we have employed an adapter-based differential display (DD) method [1]. Furthermore, using cDNA microarray and quantitative RT-PCR techniques, we have also generated a comprehensive gene expression profile consisting of 27 marker genes that are essential for discriminating leukoplakias and OSCCs [2]. To more accurately diagnose cancer subtypes, supervised learning methods have been shown previously to be the most appropriate approaches [3,4].…”

Section: Introductionmentioning

confidence: 99%

Gene expression signatures that classify the mode of invasion of primary oral squamous cell carcinomas

Kondoh

Ishikawa

Ohkura

et al. 2008

Molecular Carcinogenesis

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To identify molecular signatures and establish a new diagnostic model for progressive oral squamous cell carcinoma (OSCC). Total RNAs were isolated from primary OSCCs from both node-positive and -negative patients and used in cDNA microarray analysis. To identify marker genes representing a malignant phenotype, their expression was further examined by quantitative reverse transcription-PCR (QRT-PCR) in 64 OSCC tissues. Using Fisher's linear discriminant analysis (LDA) fitted with a stepwise increment method, we created discriminatory predictor models. The stability of these models was examined using leave-one-out cross validation. Immunohistochemical analysis was performed. Among the 16,600 possible target cDNAs in the array analysis, 83 genes demonstrated significantly differential signals (>2-fold). We further identified 53 marker genes that can be implicated in the Yamamoto-Kohama's (YKs) mode of invasion for OSCCs (P < 0.06). Using LDA fitted with a stepwise increment method, we created four discriminatory predictor models based on 16- to 25-gene signatures which could best distinguish the five established grades of YKs mode of invasion. Leave-one out validation demonstrated that the stability of these models was 92-95%. For validation, we also examined an independent set of 13 primary OSCCs; the predictor models determined the invasion status from 77% to 100% (on average, 85%) fidelity with the pathological observations. TGM3 protein expression was markedly suppressed in highly invasive OSCCs. We reveal novel gene expression alterations during the progression of OSCC, and have constructed prediction models for the evaluation of the invasion status of these cancers.

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Section: Introductionmentioning

confidence: 99%

Gene expression signatures that classify the mode of invasion of primary oral squamous cell carcinomas

Kondoh

Ishikawa

Ohkura

et al. 2008

Molecular Carcinogenesis

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“…Next, comprehensive gene expression was compared between Sq-1979 and L cells to identify differentially expressed mRNAs. Our previous studies demonstrated that the expression of certain mRNAs, such as keratin1 and transglutaminase 3, exhibit continual changes from pre-cancerous to cancerous tissues and to further malignant OSCCs (4,9). In the present study, it was revealed that the expression of certain marker mRNAs could be an index for evaluating the histological grading of precancerous and OSCC tissues obtained from patients.…”

Section: Introductionmentioning

confidence: 47%

“…To examine the transplantability, 1x10 4 , 1x10 5 , 1x10 6 or 1x10 7 Sq-1979, Sq-1979-1, 23-1, 233-11, L2-3, L3-5, L5-11, L6-8 and L6-9 cells were injected subcutaneously into the lateroabdominal area of male, 6-week-old, C3H/HeN mice (n=5 per experiment). After 1 month, mice bearing tumors (>4 mm) were counted as positive animals.…”

Section: Methodsmentioning

confidence: 99%

“…An adapter-based differential display method was previously employed to elucidate the wide range of genetic events occurring during OSCC development from pre-cancerous leukoplakia (LP) (3). A comprehensive gene expression profile was also generated to discriminate between LPs and OSCCs (4). Following therapy, metastasis has proven to be a main cause of local relapse in patients with OSCC.…”

Section: Introductionmentioning

confidence: 99%

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Gene expression analyses associated with malignant phenotypes of metastatic sub-clones derived from a mouse oral squamous cell carcinoma Sq-1979 cell line

et al. 2017

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Abstract. To elucidate the genetic events that occur during the development of OSCC, the present study established a model of oral malignancy using a mouse oral squamous cell carcinoma (OSCC) Sq-1979 cell line. Sq-1979 cells were implanted into syngeneic C3H mice. Subsequently, 233 cells and metastatic sub-clones (L cells) from primary OSCC, as well as the metastasized lymph node tissues of Sq-1979-implanted mice were established. Compared with parental Sq-1979 and 233 cells, the majority of L cells exhibited a higher proliferation rate and transplantability, and conferred a lower survival rate on the implanted mice. To investigate the genetic background of L cells, preferentially expressed genes in L cells were identified by cDNA microarray and reverse transcription-polymerase chain reaction analyses. The expression of FYN-binding protein (Fyb), solute carrier family 16 member 13 (Slc16a13), keratin 7, transmembrane portion 173 and Slc44a3 mRNAs was significantly elevated in L cells compared with that in Sq1979 and 233 cells. The mRNA expression was also evaluated in human OSCC and leukoplakia (LP) tissues. Among the 5 aforementioned mRNAs, the expression of FYB and SLC16A13 was significantly higher in OSCC than in LP tissues. Furthermore, the expression of SLC16A13 mRNA was significantly elevated in highly invasive OSCCs, which were classified as grades 3 and 4 by the Yamamoto-Kohama (YK) classification of invasion, compared with those in lower grades (YK-1 and -2). The model proposed in the present study could thus describe essential marker genes for the diagnosis of oral malignancies.

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“…In recent years, modern high-throughput genomic approaches have emerged as a means of rapidly identifying candidate genes that are associated with carcinogenesis, including those for olK (17)(18)(19). However, the concordance among different studies on marker genes of carcinogenesis of olK is low.…”

Section: Introductionmentioning

confidence: 99%

Identification of genes related to carcinogenesis of oral leukoplakia by oligo cancer microarray analysis

Liu

Wen-ling²,

Xie³

et al. 2011

Oncol Rep

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Abstract. the aim of this study was to identify genes that are predictive of carcinogenic change in patients of oral leukoplakia (olK) using a cancer-related microarray. candidate biomarkers were discovered using the oligo geArray oHs-802 and validated on independent samples by semi-quantitative reverse transcription-pcr (rt-pcr) and real-time rt-pcr. Both the discovery and the validation cohorts of samples included normal oral tissues, olK tissues and oral squamous cell carcinoma (oscc) tissues. Based on the microarray results, we found that there were nine genes successively up-regulated or down-regulated more than 2-fold between the normal group and olK group and then again between the olK group and oscc group. the expression levels of the nine signature genes had statistically significant differences (p<0.05) between the olK and normal groups and between the oscc and olK groups. In summary, the expression of the 9 signature genes might be representative of olK carcinogenesis. A cancer-related microarray was used to identify a panel of candidate biomarkers for determining carcinogenesis of olK lesions, in combination with semi-quantitative and real-time rt-pcr to validate the results. our data indicated that alterations in gene expression that result in carcinogenesis can be identified in precancerous oral tissues.

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Gene expression signatures that can discriminate oral leukoplakia subtypes and squamous cell carcinoma

Cited by 40 publications

References 24 publications

Gene expression signatures that classify the mode of invasion of primary oral squamous cell carcinomas

Gene expression signatures that classify the mode of invasion of primary oral squamous cell carcinomas

Gene expression analyses associated with malignant phenotypes of metastatic sub-clones derived from a mouse oral squamous cell carcinoma Sq-1979 cell line

Identification of genes related to carcinogenesis of oral leukoplakia by oligo cancer microarray analysis

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