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Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries.

Silveira NJ, Varuzza L, Machado-Lima A, Lauretto MS, Pinheiro DG, Rodrigues RV, Severino P, Nobrega FG, Head and Neck Genome Project GENCAPOSilva WA, de B Pereira CA, Tajara EH - BMC Med Genomics (2008)

Bottom Line: As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues.Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development.This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, UNIVAP, São José dos Campos, SP, Brazil. nelsonjfs@univap.br

ABSTRACT

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes.

Methods: Aiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries.

Results: Statistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2, MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation of BST2 and MFAP2 and the downregulation of KRT31 when samples of HNSCC were compared to tumor-free surgical margins. As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues.

Conclusion: To the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.

No MeSH data available.


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Chi-square p-value versus Kemp value for low-abundance tags.
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Figure 3: Chi-square p-value versus Kemp value for low-abundance tags.

Mentions: Since several authors have reported that chi-square test is the most appropriate for SAGE experiments [25-28], we compared the performance of our statistical approach (named here as Kemp method) with that of chi-square test. For this comparison, the SAGE data set was divided into two groups: the low-abundance tags with counts equal and lower than 50, and the high abundance tags expressed at higher levels (> 50). Good correspondence between the data obtained by both tests was found for the latter tag group (Figure 2), indicating that they are equivalent for the analysis of highly expressed sequences. A similar result was not observed for low-abundance tags (Figure 3).


Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries.

Silveira NJ, Varuzza L, Machado-Lima A, Lauretto MS, Pinheiro DG, Rodrigues RV, Severino P, Nobrega FG, Head and Neck Genome Project GENCAPOSilva WA, de B Pereira CA, Tajara EH - BMC Med Genomics (2008)

Chi-square p-value versus Kemp value for low-abundance tags.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2629771&req=5

Figure 3: Chi-square p-value versus Kemp value for low-abundance tags.
Mentions: Since several authors have reported that chi-square test is the most appropriate for SAGE experiments [25-28], we compared the performance of our statistical approach (named here as Kemp method) with that of chi-square test. For this comparison, the SAGE data set was divided into two groups: the low-abundance tags with counts equal and lower than 50, and the high abundance tags expressed at higher levels (> 50). Good correspondence between the data obtained by both tests was found for the latter tag group (Figure 2), indicating that they are equivalent for the analysis of highly expressed sequences. A similar result was not observed for low-abundance tags (Figure 3).

Bottom Line: As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues.Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development.This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, UNIVAP, São José dos Campos, SP, Brazil. nelsonjfs@univap.br

ABSTRACT

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes.

Methods: Aiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries.

Results: Statistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2, MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation of BST2 and MFAP2 and the downregulation of KRT31 when samples of HNSCC were compared to tumor-free surgical margins. As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues.

Conclusion: To the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.

No MeSH data available.


Related in: MedlinePlus