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Transcriptome profiles of carcinoma-in-situ and invasive non-small cell lung cancer as revealed by SAGE.

Lonergan KM, Chari R, Coe BP, Wilson IM, Tsao MS, Ng RT, Macaulay C, Lam S, Lam WL - PLoS ONE (2010)

Bottom Line: Expression of genes associated with epidermal development, and loss of expression of genes associated with mucociliary biology, are predominant features of CIS, largely shared with precancerous lesions.Additionally, expression of genes associated with xenobiotic metabolism/detoxification is a notable feature of CIS, and is largely maintained in invasive cancer.Additionally, up-regulated genes detected at extreme differences between CIS and invasive cancer may have potential to serve as biomarkers for early detection.

View Article: PubMed Central - PubMed

Affiliation: Genetics Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.

ABSTRACT

Background: Non-small cell lung cancer (NSCLC) presents as a progressive disease spanning precancerous, preinvasive, locally invasive, and metastatic lesions. Identification of biological pathways reflective of these progressive stages, and aberrantly expressed genes associated with these pathways, would conceivably enhance therapeutic approaches to this devastating disease.

Methodology/principal findings: Through the construction and analysis of SAGE libraries, we have determined transcriptome profiles for preinvasive carcinoma-in-situ (CIS) and invasive squamous cell carcinoma (SCC) of the lung, and compared these with expression profiles generated from both bronchial epithelium, and precancerous metaplastic and dysplastic lesions using Ingenuity Pathway Analysis. Expression of genes associated with epidermal development, and loss of expression of genes associated with mucociliary biology, are predominant features of CIS, largely shared with precancerous lesions. Additionally, expression of genes associated with xenobiotic metabolism/detoxification is a notable feature of CIS, and is largely maintained in invasive cancer. Genes related to tissue fibrosis and acute phase immune response are characteristic of the invasive SCC phenotype. Moreover, the data presented here suggests that tissue remodeling/fibrosis is initiated at the early stages of CIS. Additionally, this study indicates that alteration in copy-number status represents a plausible mechanism for differential gene expression in CIS and invasive SCC.

Conclusions/significance: This study is the first report of large-scale expression profiling of CIS of the lung. Unbiased expression profiling of these preinvasive and invasive lesions provides a platform for further investigations into the molecular genetic events relevant to early stages of squamous NSCLC development. Additionally, up-regulated genes detected at extreme differences between CIS and invasive cancer may have potential to serve as biomarkers for early detection.

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Related in: MedlinePlus

IPA canonical pathways analysis and toxicity lists analysis of the CIS over BE_PC and the SCC over BE_PC datasets.For analysis of the CIS over BE_PC dataset, 109 IPA mapped IDs were eligible; for analysis of the SCC over BE_PC dataset, 153 IPA mapped IDs were eligible. The two sets of data were displayed together using IPA core comparisons, and the 10 most significant functions within Canonical Pathways and Toxicity Lists are shown above for each dataset. The data in A and C is sorted according to highest significance in CIS over BE_PC, and the data in B and D is sorted according to highest significance in SCC over BE_PC. The orange line indicates the threshold limit of significance, preset at a p-value of 0.05.
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pone-0009162-g006: IPA canonical pathways analysis and toxicity lists analysis of the CIS over BE_PC and the SCC over BE_PC datasets.For analysis of the CIS over BE_PC dataset, 109 IPA mapped IDs were eligible; for analysis of the SCC over BE_PC dataset, 153 IPA mapped IDs were eligible. The two sets of data were displayed together using IPA core comparisons, and the 10 most significant functions within Canonical Pathways and Toxicity Lists are shown above for each dataset. The data in A and C is sorted according to highest significance in CIS over BE_PC, and the data in B and D is sorted according to highest significance in SCC over BE_PC. The orange line indicates the threshold limit of significance, preset at a p-value of 0.05.

Mentions: We utilized IPA core analysis to identify additional functions within the CIS and invasive SCC datasets of up-regulated genes (Figure 6). Canonical Pathways analysis and Toxicity Lists analysis identified metabolism/detoxification of xenobiotics as a component of the CIS dataset, and hepatic fibrosis as a major characteristic of the invasive cancer phenotype. Specific genes associated with these phenotypes are listed in Table 5 and Table 6 and described below.


Transcriptome profiles of carcinoma-in-situ and invasive non-small cell lung cancer as revealed by SAGE.

Lonergan KM, Chari R, Coe BP, Wilson IM, Tsao MS, Ng RT, Macaulay C, Lam S, Lam WL - PLoS ONE (2010)

IPA canonical pathways analysis and toxicity lists analysis of the CIS over BE_PC and the SCC over BE_PC datasets.For analysis of the CIS over BE_PC dataset, 109 IPA mapped IDs were eligible; for analysis of the SCC over BE_PC dataset, 153 IPA mapped IDs were eligible. The two sets of data were displayed together using IPA core comparisons, and the 10 most significant functions within Canonical Pathways and Toxicity Lists are shown above for each dataset. The data in A and C is sorted according to highest significance in CIS over BE_PC, and the data in B and D is sorted according to highest significance in SCC over BE_PC. The orange line indicates the threshold limit of significance, preset at a p-value of 0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2820080&req=5

pone-0009162-g006: IPA canonical pathways analysis and toxicity lists analysis of the CIS over BE_PC and the SCC over BE_PC datasets.For analysis of the CIS over BE_PC dataset, 109 IPA mapped IDs were eligible; for analysis of the SCC over BE_PC dataset, 153 IPA mapped IDs were eligible. The two sets of data were displayed together using IPA core comparisons, and the 10 most significant functions within Canonical Pathways and Toxicity Lists are shown above for each dataset. The data in A and C is sorted according to highest significance in CIS over BE_PC, and the data in B and D is sorted according to highest significance in SCC over BE_PC. The orange line indicates the threshold limit of significance, preset at a p-value of 0.05.
Mentions: We utilized IPA core analysis to identify additional functions within the CIS and invasive SCC datasets of up-regulated genes (Figure 6). Canonical Pathways analysis and Toxicity Lists analysis identified metabolism/detoxification of xenobiotics as a component of the CIS dataset, and hepatic fibrosis as a major characteristic of the invasive cancer phenotype. Specific genes associated with these phenotypes are listed in Table 5 and Table 6 and described below.

Bottom Line: Expression of genes associated with epidermal development, and loss of expression of genes associated with mucociliary biology, are predominant features of CIS, largely shared with precancerous lesions.Additionally, expression of genes associated with xenobiotic metabolism/detoxification is a notable feature of CIS, and is largely maintained in invasive cancer.Additionally, up-regulated genes detected at extreme differences between CIS and invasive cancer may have potential to serve as biomarkers for early detection.

View Article: PubMed Central - PubMed

Affiliation: Genetics Unit, Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada.

ABSTRACT

Background: Non-small cell lung cancer (NSCLC) presents as a progressive disease spanning precancerous, preinvasive, locally invasive, and metastatic lesions. Identification of biological pathways reflective of these progressive stages, and aberrantly expressed genes associated with these pathways, would conceivably enhance therapeutic approaches to this devastating disease.

Methodology/principal findings: Through the construction and analysis of SAGE libraries, we have determined transcriptome profiles for preinvasive carcinoma-in-situ (CIS) and invasive squamous cell carcinoma (SCC) of the lung, and compared these with expression profiles generated from both bronchial epithelium, and precancerous metaplastic and dysplastic lesions using Ingenuity Pathway Analysis. Expression of genes associated with epidermal development, and loss of expression of genes associated with mucociliary biology, are predominant features of CIS, largely shared with precancerous lesions. Additionally, expression of genes associated with xenobiotic metabolism/detoxification is a notable feature of CIS, and is largely maintained in invasive cancer. Genes related to tissue fibrosis and acute phase immune response are characteristic of the invasive SCC phenotype. Moreover, the data presented here suggests that tissue remodeling/fibrosis is initiated at the early stages of CIS. Additionally, this study indicates that alteration in copy-number status represents a plausible mechanism for differential gene expression in CIS and invasive SCC.

Conclusions/significance: This study is the first report of large-scale expression profiling of CIS of the lung. Unbiased expression profiling of these preinvasive and invasive lesions provides a platform for further investigations into the molecular genetic events relevant to early stages of squamous NSCLC development. Additionally, up-regulated genes detected at extreme differences between CIS and invasive cancer may have potential to serve as biomarkers for early detection.

Show MeSH
Related in: MedlinePlus