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Analysis of ASCL1-Positive Subgroup of Non-Small Cell Lung Cancer
Description
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A2686 - Analysis of ASCL1-Positive Subgroup of Non-Small Cell Lung Cancer
Author Block: N. Miyashita1, M. Horie2, A. Saito1, T. Nagase1; 1Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan, 2University of Southern California, Southern California, CA, United States.
Background
ASCL1 is a basic helix-loop-helix (bHLH) transcription factor that functions as a master regulator of neuroendocrine differentiation. ASCL1 shows high expression levels not only in neuroendocrine tumors but also in part of non-small cell lung cancer (NSCLC). However, clinical features of ASCL1-positive NSCLC are uncertain.
Methods
We analyzed public datasets of gene expression profiling (CAGE-seq and RNA-seq) and studied transcriptome characteristics of ASCL1-positive NSCLC. In addition, we examined functions and target genes of ASCL1 in ASCL1-positive lung adenocarcinoma cell line, VMRC-LCD.
Results
ASCL1 was positive in about 15% of lung adenocarcinoma tissue samples of different datasets, most of which were EGFR mutation-negative. ASCL1-positive NSCLC samples showed characteristic gene expression profiles marked by genes related to neuroendocrine differentiation. Similarly, distinct transcriptional profiles were noted in ASCL1-positive lung adenocarcinoma cell lines in clear contrast to ASCL1-negative cell lines. Silencing of ASCL1 in VMRC-LCD resulted in suppressed cell proliferation and induction of apoptosis. RNA-seq analysis identified genes possibly regulated by ASCL1. Notably, super-enhancer-related genes were preferentially downregulated by ASCL1 knockdown. Analysis of a large-scale drug screening dataset suggested that ASCL1-positive cell lines had higher sensitivity to several molecular targeted drugs.
Conclusion
There is a subgroup of NSCLC (mostly adenocarcinoma) characterized by ASCL1 expression, neuroendocrine features and distinct gene expression profiles. ASCL1-positive NSCLC may be more responsive to certain targeted therapies. In this regard, recognition of this subgroup would be clinically important.
Author Block: N. Miyashita1, M. Horie2, A. Saito1, T. Nagase1; 1Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan, 2University of Southern California, Southern California, CA, United States.
Background
ASCL1 is a basic helix-loop-helix (bHLH) transcription factor that functions as a master regulator of neuroendocrine differentiation. ASCL1 shows high expression levels not only in neuroendocrine tumors but also in part of non-small cell lung cancer (NSCLC). However, clinical features of ASCL1-positive NSCLC are uncertain.
Methods
We analyzed public datasets of gene expression profiling (CAGE-seq and RNA-seq) and studied transcriptome characteristics of ASCL1-positive NSCLC. In addition, we examined functions and target genes of ASCL1 in ASCL1-positive lung adenocarcinoma cell line, VMRC-LCD.
Results
ASCL1 was positive in about 15% of lung adenocarcinoma tissue samples of different datasets, most of which were EGFR mutation-negative. ASCL1-positive NSCLC samples showed characteristic gene expression profiles marked by genes related to neuroendocrine differentiation. Similarly, distinct transcriptional profiles were noted in ASCL1-positive lung adenocarcinoma cell lines in clear contrast to ASCL1-negative cell lines. Silencing of ASCL1 in VMRC-LCD resulted in suppressed cell proliferation and induction of apoptosis. RNA-seq analysis identified genes possibly regulated by ASCL1. Notably, super-enhancer-related genes were preferentially downregulated by ASCL1 knockdown. Analysis of a large-scale drug screening dataset suggested that ASCL1-positive cell lines had higher sensitivity to several molecular targeted drugs.
Conclusion
There is a subgroup of NSCLC (mostly adenocarcinoma) characterized by ASCL1 expression, neuroendocrine features and distinct gene expression profiles. ASCL1-positive NSCLC may be more responsive to certain targeted therapies. In this regard, recognition of this subgroup would be clinically important.
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