PMC:3475481 / 5969-9243 JSONTXT

{"project":"2_test","denotations":[{"id":"23105925-19646959-44845471","span":{"begin":1593,"end":1594},"obj":"19646959"},{"id":"23105925-19029817-44845472","span":{"begin":1603,"end":1604},"obj":"19029817"},{"id":"23105925-17510972-44845473","span":{"begin":1614,"end":1615},"obj":"17510972"},{"id":"23105925-18538015-44845474","span":{"begin":1624,"end":1625},"obj":"18538015"},{"id":"23105925-18460737-44845475","span":{"begin":1635,"end":1637},"obj":"18460737"},{"id":"23105925-18254958-44845476","span":{"begin":1646,"end":1648},"obj":"18254958"},{"id":"23105925-19487542-44845477","span":{"begin":1650,"end":1652},"obj":"19487542"},{"id":"23105925-18254958-44845478","span":{"begin":1666,"end":1668},"obj":"18254958"},{"id":"23105925-18476518-44845479","span":{"begin":1700,"end":1702},"obj":"18476518"},{"id":"23105925-19596857-44845479","span":{"begin":1700,"end":1702},"obj":"19596857"},{"id":"23105925-17559122-44845479","span":{"begin":1700,"end":1702},"obj":"17559122"},{"id":"23105925-16351756-44845479","span":{"begin":1700,"end":1702},"obj":"16351756"},{"id":"23105925-19091943-44845479","span":{"begin":1700,"end":1702},"obj":"19091943"},{"id":"23105925-17448016-44845479","span":{"begin":1700,"end":1702},"obj":"17448016"},{"id":"23105925-19251594-44845479","span":{"begin":1700,"end":1702},"obj":"19251594"},{"id":"23105925-17720884-44845479","span":{"begin":1700,"end":1702},"obj":"17720884"},{"id":"23105925-16631473-44845479","span":{"begin":1700,"end":1702},"obj":"16631473"},{"id":"23105925-19885841-44845479","span":{"begin":1700,"end":1702},"obj":"19885841"},{"id":"23105925-18686028-44845479","span":{"begin":1700,"end":1702},"obj":"18686028"},{"id":"23105925-1691065-44845479","span":{"begin":1700,"end":1702},"obj":"1691065"},{"id":"23105925-14707456-44845479","span":{"begin":1700,"end":1702},"obj":"14707456"},{"id":"23105925-16619573-44845479","span":{"begin":1700,"end":1702},"obj":"16619573"},{"id":"23105925-19358268-44845479","span":{"begin":1700,"end":1702},"obj":"19358268"},{"id":"23105925-19240718-44845479","span":{"begin":1700,"end":1702},"obj":"19240718"},{"id":"23105925-19857786-44845479","span":{"begin":1700,"end":1702},"obj":"19857786"},{"id":"23105925-19459850-44845479","span":{"begin":1700,"end":1702},"obj":"19459850"},{"id":"23105925-17439397-44845479","span":{"begin":1700,"end":1702},"obj":"17439397"},{"id":"23105925-19671159-44845479","span":{"begin":1700,"end":1702},"obj":"19671159"},{"id":"23105925-19655089-44845479","span":{"begin":1700,"end":1702},"obj":"19655089"},{"id":"23105925-17091453-44845479","span":{"begin":1700,"end":1702},"obj":"17091453"},{"id":"23105925-19738056-44845479","span":{"begin":1700,"end":1702},"obj":"19738056"},{"id":"23105925-19690970-44845479","span":{"begin":1700,"end":1702},"obj":"19690970"},{"id":"23105925-19584233-44845479","span":{"begin":1700,"end":1702},"obj":"19584233"},{"id":"23105925-17339605-44845479","span":{"begin":1700,"end":1702},"obj":"17339605"},{"id":"23105925-17569615-44845479","span":{"begin":1700,"end":1702},"obj":"17569615"},{"id":"23105925-18024791-44845479","span":{"begin":1700,"end":1702},"obj":"18024791"},{"id":"23105925-19330027-44845479","span":{"begin":1700,"end":1702},"obj":"19330027"},{"id":"23105925-19861535-44845479","span":{"begin":1700,"end":1702},"obj":"19861535"},{"id":"23105925-19536649-44845479","span":{"begin":1700,"end":1702},"obj":"19536649"},{"id":"23105925-19010856-44845479","span":{"begin":1700,"end":1702},"obj":"19010856"},{"id":"23105925-19902052-44845479","span":{"begin":1700,"end":1702},"obj":"19902052"},{"id":"23105925-15196853-44845479","span":{"begin":1700,"end":1702},"obj":"15196853"},{"id":"23105925-17234784-44845479","span":{"begin":1700,"end":1702},"obj":"17234784"},{"id":"23105925-15205458-44845479","span":{"begin":1700,"end":1702},"obj":"15205458"},{"id":"23105925-17102582-44845479","span":{"begin":1700,"end":1702},"obj":"17102582"},{"id":"23105925-16839881-44845479","span":{"begin":1700,"end":1702},"obj":"16839881"},{"id":"23105925-17555561-44845479","span":{"begin":1700,"end":1702},"obj":"17555561"},{"id":"23105925-17389037-44845479","span":{"begin":1700,"end":1702},"obj":"17389037"},{"id":"23105925-19896966-44845479","span":{"begin":1700,"end":1702},"obj":"19896966"},{"id":"23105925-19324446-44845479","span":{"begin":1700,"end":1702},"obj":"19324446"},{"id":"23105925-19118053-44845479","span":{"begin":1700,"end":1702},"obj":"19118053"}],"text":"Results\nThe clinical information and expression levels of two datasets are summarized in Table 4 and Fig. 1. Subgroup and sex were similarly distributed in the two datasets. The distributions of other factors were not included.\nThe scale of expression levels in the two datasets was different; the expression values of Data 2004 ranged from 0.01 to 740, and those of Data 2005 were from 0.1 to 19,773. The expression patterns of the two datasets can be explored in Fig. 1.\nLots of outliers are shown in Fig. 1A in the two datasets containing whole gene sets. However, in subsets of significant genes, the expression ranges got narrow, and the outliers were decreased (Fig. 1B). The expressions of tumor tissues in Data 2004 were upregulated and varied compared with normal tissues. If there was no outlier with a maximum value in the 14th tumor tissue in Data 2004, the expressions of the two different groups would be clearly distinguished. Any clear differences in expression were not shown between the two groups in Data 2005.\n\nUpregulated 51 genes in oral squamous cell carcinoma\nTo identify differently expressed genes between normal and tumor tissues, we performed chi-square test using a combined microarray dataset. Fifty-one significant genes were selected from a combined dataset with p-value less than 0.005, which were upregulated in OSCC tissues. The significance level can be controlled, and more genes can be selected with a lower significance level. These selected genes are summarized in Table 5.\nMany genes among the selected genes were known as cancer-related genes. STAT1 [6], SKP2 [7], IFI16 [8], RHEB [9], FIF44 [10], SOD2 [11, 12], and GREM1 [11] are related to OSCC. Table 6 [13-56] summarizes the previous studies that have published the relations of selected genes with cancer.\n\nExpression pattern of the identified genes\nTo investigate whether the different experimental groups could be classified with significant genes, an unsupervised hierarchical clustering method was applied to the significant gene set (Fig. 2).\nThe normal group consisted of 4 tissues and showed significantly lower expression levels when compared with the tumor group. In Fig. 2, we investigated the classification availability of the identified genes in Data 2004, not in a combined dataset, because the two datasets have different expression scales.\n\nNetwork analysis\nBased on all identified genes, new and expanded pathway maps and connections and specific gene-gene interactions were inferred, functionally analyzed, and used to build on the existing pathway using the Ingenuity Pathway Analysis (IPA) knowledge base [57].\nTo generate networks in this work, the knowledge base was queried for interactions between the identified genes and all other genes stored in the database. Four networks were found to be significant in OSCC. The network with the highest score (Network 1, score = 36) was generated, with 17 identified genes (Table 7, Fig. 3).\nIn the network diagram, STAT1 and SOD2 neighbored with NMI and AURKA, respectively. The expression levels of STAT1 and SOD2 could be expected to be related with those of NMI and SOD2. Actually, the expressions of STAT1 and SOD2 were strongly positively correlated with NMI (r = 0.95) and AURKA (r = 0.87), respectively."}