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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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Detection of carcinoma-in-situ bronchial lesions.Bronchoscopy using A. white light for detection of CIS lesions (indicated by arrow), or B. LIFE (lung-imagine fluorescent endoscopy) for detection of CIS lesions (indicated by arrow). C. Histological section identifying a CIS lesion within the bronchial epithelium, typified by extensive squamous stratification.
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pone-0009162-g001: Detection of carcinoma-in-situ bronchial lesions.Bronchoscopy using A. white light for detection of CIS lesions (indicated by arrow), or B. LIFE (lung-imagine fluorescent endoscopy) for detection of CIS lesions (indicated by arrow). C. Histological section identifying a CIS lesion within the bronchial epithelium, typified by extensive squamous stratification.

Mentions: Carcinoma-in-situ (CIS) of the lung, are preinvasive lesions of squamous NSCLC, frequently associated with histological, cytological, and genetic aberrations, and progression to invasive cancer typically ensues [9], [10], [11], [12]. As these minute lesions are optimally visible in the central airways by fluorescent bronchoscopy or LIFE (lung-imaging fluorescent endoscopy) [13], [14], experimental and clinical studies are rare (Figure 1). Although many expression profiling studies have been reported for advanced stage lung tumors [15], [16], early stage (CIS and locally invasive) lesions remain largely unexplored. Molecular genetic analysis of preinvasive lesions, free from background noise associated with commonly studied advanced tumors, is essential to the identification of key genes and corresponding molecular pathways underlying early events in neoplastic transformation and cancer development. An understanding of these early aberrations is essential for prompt therapeutic intervention of this devastating disease.


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)

Detection of carcinoma-in-situ bronchial lesions.Bronchoscopy using A. white light for detection of CIS lesions (indicated by arrow), or B. LIFE (lung-imagine fluorescent endoscopy) for detection of CIS lesions (indicated by arrow). C. Histological section identifying a CIS lesion within the bronchial epithelium, typified by extensive squamous stratification.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2820080&req=5

pone-0009162-g001: Detection of carcinoma-in-situ bronchial lesions.Bronchoscopy using A. white light for detection of CIS lesions (indicated by arrow), or B. LIFE (lung-imagine fluorescent endoscopy) for detection of CIS lesions (indicated by arrow). C. Histological section identifying a CIS lesion within the bronchial epithelium, typified by extensive squamous stratification.
Mentions: Carcinoma-in-situ (CIS) of the lung, are preinvasive lesions of squamous NSCLC, frequently associated with histological, cytological, and genetic aberrations, and progression to invasive cancer typically ensues [9], [10], [11], [12]. As these minute lesions are optimally visible in the central airways by fluorescent bronchoscopy or LIFE (lung-imaging fluorescent endoscopy) [13], [14], experimental and clinical studies are rare (Figure 1). Although many expression profiling studies have been reported for advanced stage lung tumors [15], [16], early stage (CIS and locally invasive) lesions remain largely unexplored. Molecular genetic analysis of preinvasive lesions, free from background noise associated with commonly studied advanced tumors, is essential to the identification of key genes and corresponding molecular pathways underlying early events in neoplastic transformation and cancer development. An understanding of these early aberrations is essential for prompt therapeutic intervention of this devastating disease.

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