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The evolving transcriptome of head and neck squamous cell carcinoma: a systematic review.

Yu YH, Kuo HK, Chang KW - PLoS ONE (2008)

Bottom Line: In total, 1442 genes were verified, i.e. reported at least twice, with ECM1, EMP1, CXCL10 and POSTN shown to be highly reported across all three stages.Notably, functional estimates derived from topological characteristics of integrin signaling networks identified such important genes as ITGA3 and ITGA5, which were supported by findings of invasiveness in vitro.Moreover, we computed genome-wide probabilities of reporting differential gene activities for the Pre, TvN, and Meta stages, respectively.

View Article: PubMed Central - PubMed

Affiliation: School of Dentistry, National Yang-Ming University, Taipei, Taiwan. yauhuayu@gmail.com

ABSTRACT

Background: Numerous studies were performed to illuminate mechanisms of tumorigenesis and metastases from gene expression profiles of Head and Neck Squamous Cell Carcinoma (HNSCC). The objective of this review is to conduct a network-based meta-analysis to identify the underlying biological signatures of the HNSCC transcriptome.

Methods and findings: We included 63 HNSCC transcriptomic studies into three specific categories of comparisons: Pre, premalignant lesions v.s. normal; TvN, primary tumors v.s. normal; and Meta, metastatic or invasive v.s. primary tumors. Reported genes extracted from the literature were systematically analyzed. Participation of differential gene activities across three progressive stages deciphered the evolving nature of HNSCC. In total, 1442 genes were verified, i.e. reported at least twice, with ECM1, EMP1, CXCL10 and POSTN shown to be highly reported across all three stages. Knowledge-based networks of the HNSCC transcriptome were constructed, demonstrating integrin signaling and antigen presentation pathways as highly enriched. Notably, functional estimates derived from topological characteristics of integrin signaling networks identified such important genes as ITGA3 and ITGA5, which were supported by findings of invasiveness in vitro. Moreover, we computed genome-wide probabilities of reporting differential gene activities for the Pre, TvN, and Meta stages, respectively. Results highlighted chromosomal regions of 6p21, 19p13 and 19q13, where genomic alterations were shown to be correlated with the nodal status of HNSCC.

Conclusions: By means of a systems-biology approach via network-based meta-analyses, we provided a deeper insight into the evolving nature of the HNSCC transcriptome. Enriched canonical signaling pathways, hot-spots of transcriptional profiles across the genome, as well as topologically significant genes derived from network analyses were highlighted for each of the three progressive stages, Pre, TvN, and Meta, respectively.

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Related in: MedlinePlus

Ranking of the enriched canonical pathways.Eight canonical pathways were found in consensus in IPA with the full gene lists (all) or the verified gene lists (fq2) as inputs. Embedded table showed rankings of the canonical pathways in different analyses. Antigen presentation, calcium signaling, and integrin signaling pathways were highlighted as highly enriched across three progressive stages. For each stage of the HNSCC transcriptome, figure panels demonstrated the enriched canonical pathways ranked by the −log (p-values) (right y-axis), that is, the orange line with square data points. Colored bars were indicating the percentage (left y-axis) of the up- or down-regulated genes within each canonical pathway. The numbers on top of the colored bars were the number of total genes in the canonical pathways.
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pone-0003215-g002: Ranking of the enriched canonical pathways.Eight canonical pathways were found in consensus in IPA with the full gene lists (all) or the verified gene lists (fq2) as inputs. Embedded table showed rankings of the canonical pathways in different analyses. Antigen presentation, calcium signaling, and integrin signaling pathways were highlighted as highly enriched across three progressive stages. For each stage of the HNSCC transcriptome, figure panels demonstrated the enriched canonical pathways ranked by the −log (p-values) (right y-axis), that is, the orange line with square data points. Colored bars were indicating the percentage (left y-axis) of the up- or down-regulated genes within each canonical pathway. The numbers on top of the colored bars were the number of total genes in the canonical pathways.

Mentions: The bounded fold changes of the full gene lists and the verified gene lists of three comparisons, Pre, TvN, and Meta, were imported into the Ingenuity Pathways Analysis (IPA) Software (Ingenuity Systems, Redwood City, CA, USA) to obtain six sets of networks for further analyses. We used IPA to identify the top 10 enriched canonical pathways for each stage of comparison (Fig. 2). The enriched canonical pathways were ranked by the p-values of the Fisher's exact test, which indicated the probabilities of the input genes to be associated with genes in the canonical pathways expected by chance.


The evolving transcriptome of head and neck squamous cell carcinoma: a systematic review.

Yu YH, Kuo HK, Chang KW - PLoS ONE (2008)

Ranking of the enriched canonical pathways.Eight canonical pathways were found in consensus in IPA with the full gene lists (all) or the verified gene lists (fq2) as inputs. Embedded table showed rankings of the canonical pathways in different analyses. Antigen presentation, calcium signaling, and integrin signaling pathways were highlighted as highly enriched across three progressive stages. For each stage of the HNSCC transcriptome, figure panels demonstrated the enriched canonical pathways ranked by the −log (p-values) (right y-axis), that is, the orange line with square data points. Colored bars were indicating the percentage (left y-axis) of the up- or down-regulated genes within each canonical pathway. The numbers on top of the colored bars were the number of total genes in the canonical pathways.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2533097&req=5

pone-0003215-g002: Ranking of the enriched canonical pathways.Eight canonical pathways were found in consensus in IPA with the full gene lists (all) or the verified gene lists (fq2) as inputs. Embedded table showed rankings of the canonical pathways in different analyses. Antigen presentation, calcium signaling, and integrin signaling pathways were highlighted as highly enriched across three progressive stages. For each stage of the HNSCC transcriptome, figure panels demonstrated the enriched canonical pathways ranked by the −log (p-values) (right y-axis), that is, the orange line with square data points. Colored bars were indicating the percentage (left y-axis) of the up- or down-regulated genes within each canonical pathway. The numbers on top of the colored bars were the number of total genes in the canonical pathways.
Mentions: The bounded fold changes of the full gene lists and the verified gene lists of three comparisons, Pre, TvN, and Meta, were imported into the Ingenuity Pathways Analysis (IPA) Software (Ingenuity Systems, Redwood City, CA, USA) to obtain six sets of networks for further analyses. We used IPA to identify the top 10 enriched canonical pathways for each stage of comparison (Fig. 2). The enriched canonical pathways were ranked by the p-values of the Fisher's exact test, which indicated the probabilities of the input genes to be associated with genes in the canonical pathways expected by chance.

Bottom Line: In total, 1442 genes were verified, i.e. reported at least twice, with ECM1, EMP1, CXCL10 and POSTN shown to be highly reported across all three stages.Notably, functional estimates derived from topological characteristics of integrin signaling networks identified such important genes as ITGA3 and ITGA5, which were supported by findings of invasiveness in vitro.Moreover, we computed genome-wide probabilities of reporting differential gene activities for the Pre, TvN, and Meta stages, respectively.

View Article: PubMed Central - PubMed

Affiliation: School of Dentistry, National Yang-Ming University, Taipei, Taiwan. yauhuayu@gmail.com

ABSTRACT

Background: Numerous studies were performed to illuminate mechanisms of tumorigenesis and metastases from gene expression profiles of Head and Neck Squamous Cell Carcinoma (HNSCC). The objective of this review is to conduct a network-based meta-analysis to identify the underlying biological signatures of the HNSCC transcriptome.

Methods and findings: We included 63 HNSCC transcriptomic studies into three specific categories of comparisons: Pre, premalignant lesions v.s. normal; TvN, primary tumors v.s. normal; and Meta, metastatic or invasive v.s. primary tumors. Reported genes extracted from the literature were systematically analyzed. Participation of differential gene activities across three progressive stages deciphered the evolving nature of HNSCC. In total, 1442 genes were verified, i.e. reported at least twice, with ECM1, EMP1, CXCL10 and POSTN shown to be highly reported across all three stages. Knowledge-based networks of the HNSCC transcriptome were constructed, demonstrating integrin signaling and antigen presentation pathways as highly enriched. Notably, functional estimates derived from topological characteristics of integrin signaling networks identified such important genes as ITGA3 and ITGA5, which were supported by findings of invasiveness in vitro. Moreover, we computed genome-wide probabilities of reporting differential gene activities for the Pre, TvN, and Meta stages, respectively. Results highlighted chromosomal regions of 6p21, 19p13 and 19q13, where genomic alterations were shown to be correlated with the nodal status of HNSCC.

Conclusions: By means of a systems-biology approach via network-based meta-analyses, we provided a deeper insight into the evolving nature of the HNSCC transcriptome. Enriched canonical signaling pathways, hot-spots of transcriptional profiles across the genome, as well as topologically significant genes derived from network analyses were highlighted for each of the three progressive stages, Pre, TvN, and Meta, respectively.

Show MeSH
Related in: MedlinePlus