Dataset Information

RNA-sequencing in non-small cell lung cancer shows gene downregulation of therapeutic targets in tumor tissue compared to non-malignant lung tissue.

ABSTRACT:

Background

Gene expression of specific therapeutic targets in non-malignant lung tissue might play an important role in optimizing targeted therapies. This study aims to identify different expression patterns of fifteen genes important for targeted therapy in non-small cell lung cancer (NSCLC).

Methods

We prospectively collected tissue of NSCLC and non-malignant lung tissue from 25 primary resected patients. RNA-sequencing and 450 K methylation array profiling was applied to both NSCLC and non-malignant lung tissue and data were analyzed for 14 target genes. We analyzed differential expression and methylation as well as expression according to patient characteristics like smoking status, histology, age, chronic obstructive pulmonary disease, C-reactive protein (CRP) and gender. TCGA data served as a validation set.

Results

Nineteen men and 6 women were included. Important targets like PD-L2 (p?=?0.035), VEGFR2 (p??5 mg/L. In the TCGA data but not in our primary data, PD-L1 & 2 were both borderline more expressed in tumors of active smokers vs. tumors of ex-smokers (p?=?0.044 and 0.052).

Conclusions

Our results suggest a lower PD-L1 & 2 and VEGFR expression in NSCLC vs. non-malignant lung tissue. Specific patient characteristics did not seem to change the overall expression differences as they were in line with the overall results. This information may contribute to the optimization of targeted treatments.

SUBMITTER: Reynders K

PROVIDER: S-EPMC6050654 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

RNA-sequencing in non-small cell lung cancer shows gene downregulation of therapeutic targets in tumor tissue compared to non-malignant lung tissue.

Reynders Kobe K Wauters Els E Moisse Matthieu M Decaluwé Herbert H De Leyn Paul P Peeters Stéphanie S Lambrecht Maarten M Nackaerts Kristiaan K Dooms Christophe C Janssens Wim W Vansteenkiste Johan J Lambrechts Diether D De Ruysscher Dirk D

Radiation oncology (London, England) 20180717 1

<h4>Background</h4>Gene expression of specific therapeutic targets in non-malignant lung tissue might play an important role in optimizing targeted therapies. This study aims to identify different expression patterns of fifteen genes important for targeted therapy in non-small cell lung cancer (NSCLC).<h4>Methods</h4>We prospectively collected tissue of NSCLC and non-malignant lung tissue from 25 primary resected patients. RNA-sequencing and 450 K methylation array profiling was applied to both ...[more]

PMID: 30016964

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Project description:IntroductionAtypical teratoid rhabdoid tumor (ATRT) is a lethal type of malignant rhabdoid tumor in the brain, seen mostly in children under two years old. ATRT is mainly linked to the biallelic inactivation of the SMARCB1 gene. To understand the deadly characteristics of ATRT and develop novel diagnostic and immunotherapy strategies for the treatment of ATRT, this study investigated tumor antigens, such as alpha-fetoprotein (AFP), mucin-16 (MUC16/CA125), and osteopontin (OPN), and extracellular matrix modulators, such as matrix metalloproteinases (MMPs), in different human malignant rhabdoid tumor cell lines. In addition, the roles of MMPs were also examined.Materials and methodsFive human cell lines were chosen for this study, including two ATRT cell lines, CHLA-02-ATRT and CHLA-05-ATRT; a kidney malignant rhabdoid tumor cell line, G401; and two control cell lines, human embryonic kidney HEK293 and HEK293T. Both ATRT cell lines were treated with a broad-spectrum MMP inhibitor, GM6001, to investigate the effect of MMPs on cell proliferation, viability, and expression of tumor antigens and biomarkers. Gene expression was examined using a reverse transcription polymerase chain reaction (RT-PCR), and protein expression was characterized by immunocytochemistry and flow cytometry.ResultsAll the rhabdoid tumor cell lines tested had high gene expression levels of MUC16, OPN, AFP, and MSLN. Low expression levels of neuron-specific enolase (ENO2) by the two ATRT cell lines demonstrated their lack of neuronal genotype. Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) and tissue inhibitor of metalloproteinases-2 (TIMP-2) were highly expressed in these malignant rhabdoid tumor cells, indicating their invasive phenotypes. GM6001 significantly decreased ATRT cell proliferation and the gene expression of MSLN, OPN, and several mesenchymal markers, suggesting that inhibition of MMPs may reduce the aggressiveness of rhabdoid cancer cells.ConclusionThe results obtained from this study may advance our knowledge of the molecular landscapes of human malignant rhabdoid tumors and their biomarkers for effective diagnosis and treatment. This work analyzed the expression of human malignant rhabdoid tumor antigens that may serve as biomarkers for the development of novel therapeutic strategies, such as cancer vaccines and targeted and immunotherapies targeting osteopontin and mesothelin, for the treatment of patients with ATRT and other malignant rhabdoid tumors.

Dataset Information

RNA-sequencing in non-small cell lung cancer shows gene downregulation of therapeutic targets in tumor tissue compared to non-malignant lung tissue.

Background

Methods

Results

Conclusions

Publications

RNA-sequencing in non-small cell lung cancer shows gene downregulation of therapeutic targets in tumor tissue compared to non-malignant lung tissue.

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