The evolving transcriptome of head and neck squamous cell carcinoma: a systematic review - PubMed (original) (raw)

Meta-Analysis

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

Yau-Hua Yu et al. PLoS One. 2008.

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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. QUOROM flow diagram of the systematic reviews and meta-analysis.

The diagram summarized the search strategy. In order to be included, studies had to examine the HNSCC tumor samples by means of microarray-based gene expression profiling.

Figure 2

Figure 2. 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.

Figure 3

Figure 3. Enriched antigen presentation and integrin signaling pathways in each stage of comparison of the HNSCC transcriptome.

Genes were represented by nodes and functional associations by edges. Node coloring was scaled to the bounded fold changes–red: up-regulated; green: down-regulated. Node size was proportional to the number of papers reporting this gene in the HNSCC transriptome. Edges were colored according to the stage of the HNSCC transcriptome–red: Meta; blue: TvN; and green: Pre. a–c. Merged networks of the antigen presentation pathways with nodes colored according to the bounded fold changes in Pre, TvN, and Meta, respectively. d–f. Merged networks of the integrin signaling networks with nodes colored according to the bounded fold changes in Pre, TvN, and Meta, respectively. g–i. Sub-networks of the integrin signaling pathway in the Pre, TvN and Meta stages of the HNSCC transcriptome. (For details, please see Figure S1, S2, S3, S4 and S5).

Figure 4

Figure 4. Genome-wide probabilities of the evolving HNSCC transcriptome.

a. We computed the accumulative probabilities of reporting differentially expressed genes within each cytoband along the chromosomal coordinates. Hot-spots of differential gene activities, 1p21, 6p21, 19p13 and 19q13, were highlighted. The standardized accumulative probability for each cytoband was plotted across the genome. The color schemes represented three progressive stages of the HNSCC transcriptome–red circles: Meta; blue squares: TvN; and green triangles: Pre. b. Co-localization between hot-spots of differential gene activities and previously implicated regions of genomic alterations by Weber et al. . c–d. Differential gene expression profiles–bounded fold changes - of 167 genes in 6p21 and 189 genes in 19q13 were plotted along the chromosomal coordinates for the Pre, TvN and Meta stages, respectively.

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