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Status |
Public on May 13, 2015 |
Title |
Reprogrammed myeloid cell transcriptomes in NSCLC |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor “activated/reprogrammed” stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.
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Overall design |
We sorted pure populations of the immature monocytic myeloid cells (IMMCs), neutrophils (Neu), and epithelial cells (Epi) from tumors and adjacent lung tissues of stage I-III lung adenocarcinoma patients. RNA samples (totally 17 samples) were sequenced: from tumor IMMC (n=3), Neu (n=2), Epi (n=2); from adjacent lung IMMC (n=3), Neu (n=4), Epi (n=3).
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Contributor(s) |
Durrans A, Gao D, Mittal V |
Citation(s) |
26046767 |
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Submission date |
May 12, 2015 |
Last update date |
May 15, 2019 |
Contact name |
Dingcheng Gao |
E-mail(s) |
dig2009@med.cornell.edu
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Organization name |
Weill Cornell Medical College
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Department |
CT Surgery
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Street address |
1300 York Ave
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10065 |
Country |
USA |
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Platforms (1) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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Samples (17)
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Relations |
SRA |
SRP058237 |
BioProject |
PRJNA283843 |
Supplementary file |
Size |
Download |
File type/resource |
GSE68795_NSCLC-Epi.xlsx |
1.3 Mb |
(ftp)(http) |
XLSX |
GSE68795_NSCLC-IMMC.xlsx |
1.2 Mb |
(ftp)(http) |
XLSX |
GSE68795_NSCLC-Neu.xlsx |
1.3 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
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