Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response

D. Dvornikov; M. A. Schneider; S. Ohse; M. Szczygieł; I. Titkova; M. Rosenblatt; T. Muley; A. Warth; F. J. Herth; H. Dienemann; M. Thomas; J. Timmer; M. Schilling; H. Busch; M. Boerries; M. Meister; U. Klingmüller

doi:10.1038/s41598-018-27912-1

Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response

D. Dvornikov, M. A. Schneider, S. Ohse, M. Szczygieł, I. Titkova, M. Rosenblatt, T. Muley, A. Warth, F. J. Herth, H. Dienemann, M. Thomas, J. Timmer, M. Schilling, H. Busch, M. Boerries, M. Meister, U. Klingmüller^*

^*Corresponding author for this work

Abstract

In lung cancer a deregulation of Transforming Growth Factor-β (TGFβ) signaling has been observed. Yet, the impact of TGFβ in squamous cell carcinoma of the lung (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies and showed that the stimulation of the LUSC cell line SK-MES1 with TGFβ results in an increase of migratory invasive properties. The analysis of the dynamics of gene expression by next-generation sequencing revealed that TGFβ stimulation orchestrates the upregulation of numerous motility- and actin cytoskeleton-related genes. Among these the non-muscle myosin 10 (MYO10) showed the highest upregulation in a LUSC patient cohort of the Cancer Genome Atlas (TCGA). Knockdown of MYO10 abrogated TGFβ-induced collagen gel invasion of SK-MES1 cells. The analysis of MYO10 mRNA expression in paired tissues of 151 LUSC patients with corresponding 80-month clinical follow-up data showed that the mRNA expression ratio of MYO10 in tumor and tumor-free tissue is prognostic for overall survival of LUSC patients and predictive for the response of these patients to adjuvant chemotherapy. Thus, MYO10 represents a new clinical biomarker for this aggressive disease and due to its role in cellular motility and invasion could serve as a potential molecular target for therapeutic interventions in patients with LUSC.

Original language	English
Article number	9517
Journal	Scientific Reports
Volume	8
Issue number	1
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-018-27912-1
Publication status	Published - 01.12.2018

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Dvornikov, D., Schneider, M. A., Ohse, S., Szczygieł, M., Titkova, I., Rosenblatt, M., Muley, T., Warth, A., Herth, F. J., Dienemann, H., Thomas, M., Timmer, J., Schilling, M., Busch, H., Boerries, M., Meister, M., & Klingmüller, U. (2018). Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response. Scientific Reports, 8(1), Article 9517. https://doi.org/10.1038/s41598-018-27912-1

@article{cd57fc494fc34418991be783a366868c,

title = "Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response",

abstract = "In lung cancer a deregulation of Transforming Growth Factor-β (TGFβ) signaling has been observed. Yet, the impact of TGFβ in squamous cell carcinoma of the lung (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies and showed that the stimulation of the LUSC cell line SK-MES1 with TGFβ results in an increase of migratory invasive properties. The analysis of the dynamics of gene expression by next-generation sequencing revealed that TGFβ stimulation orchestrates the upregulation of numerous motility- and actin cytoskeleton-related genes. Among these the non-muscle myosin 10 (MYO10) showed the highest upregulation in a LUSC patient cohort of the Cancer Genome Atlas (TCGA). Knockdown of MYO10 abrogated TGFβ-induced collagen gel invasion of SK-MES1 cells. The analysis of MYO10 mRNA expression in paired tissues of 151 LUSC patients with corresponding 80-month clinical follow-up data showed that the mRNA expression ratio of MYO10 in tumor and tumor-free tissue is prognostic for overall survival of LUSC patients and predictive for the response of these patients to adjuvant chemotherapy. Thus, MYO10 represents a new clinical biomarker for this aggressive disease and due to its role in cellular motility and invasion could serve as a potential molecular target for therapeutic interventions in patients with LUSC.",

author = "D. Dvornikov and Schneider, {M. A.} and S. Ohse and M. Szczygie{\l} and I. Titkova and M. Rosenblatt and T. Muley and A. Warth and Herth, {F. J.} and H. Dienemann and M. Thomas and J. Timmer and M. Schilling and H. Busch and M. Boerries and M. Meister and U. Klingm{\"u}ller",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41598-018-27912-1",

language = "English",

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issn = "2045-2322",

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Dvornikov, D, Schneider, MA, Ohse, S, Szczygieł, M, Titkova, I, Rosenblatt, M, Muley, T, Warth, A, Herth, FJ, Dienemann, H, Thomas, M, Timmer, J, Schilling, M, Busch, H, Boerries, M, Meister, M & Klingmüller, U 2018, 'Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response', Scientific Reports, vol. 8, no. 1, 9517. https://doi.org/10.1038/s41598-018-27912-1

TY - JOUR

T1 - Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response

AU - Dvornikov, D.

AU - Schneider, M. A.

AU - Ohse, S.

AU - Szczygieł, M.

AU - Titkova, I.

AU - Rosenblatt, M.

AU - Muley, T.

AU - Warth, A.

AU - Herth, F. J.

AU - Dienemann, H.

AU - Thomas, M.

AU - Timmer, J.

AU - Schilling, M.

AU - Busch, H.

AU - Boerries, M.

AU - Meister, M.

AU - Klingmüller, U.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - In lung cancer a deregulation of Transforming Growth Factor-β (TGFβ) signaling has been observed. Yet, the impact of TGFβ in squamous cell carcinoma of the lung (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies and showed that the stimulation of the LUSC cell line SK-MES1 with TGFβ results in an increase of migratory invasive properties. The analysis of the dynamics of gene expression by next-generation sequencing revealed that TGFβ stimulation orchestrates the upregulation of numerous motility- and actin cytoskeleton-related genes. Among these the non-muscle myosin 10 (MYO10) showed the highest upregulation in a LUSC patient cohort of the Cancer Genome Atlas (TCGA). Knockdown of MYO10 abrogated TGFβ-induced collagen gel invasion of SK-MES1 cells. The analysis of MYO10 mRNA expression in paired tissues of 151 LUSC patients with corresponding 80-month clinical follow-up data showed that the mRNA expression ratio of MYO10 in tumor and tumor-free tissue is prognostic for overall survival of LUSC patients and predictive for the response of these patients to adjuvant chemotherapy. Thus, MYO10 represents a new clinical biomarker for this aggressive disease and due to its role in cellular motility and invasion could serve as a potential molecular target for therapeutic interventions in patients with LUSC.

AB - In lung cancer a deregulation of Transforming Growth Factor-β (TGFβ) signaling has been observed. Yet, the impact of TGFβ in squamous cell carcinoma of the lung (LUSC) remained to be determined. We combined phenotypic and transcriptome-wide studies and showed that the stimulation of the LUSC cell line SK-MES1 with TGFβ results in an increase of migratory invasive properties. The analysis of the dynamics of gene expression by next-generation sequencing revealed that TGFβ stimulation orchestrates the upregulation of numerous motility- and actin cytoskeleton-related genes. Among these the non-muscle myosin 10 (MYO10) showed the highest upregulation in a LUSC patient cohort of the Cancer Genome Atlas (TCGA). Knockdown of MYO10 abrogated TGFβ-induced collagen gel invasion of SK-MES1 cells. The analysis of MYO10 mRNA expression in paired tissues of 151 LUSC patients with corresponding 80-month clinical follow-up data showed that the mRNA expression ratio of MYO10 in tumor and tumor-free tissue is prognostic for overall survival of LUSC patients and predictive for the response of these patients to adjuvant chemotherapy. Thus, MYO10 represents a new clinical biomarker for this aggressive disease and due to its role in cellular motility and invasion could serve as a potential molecular target for therapeutic interventions in patients with LUSC.

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U2 - 10.1038/s41598-018-27912-1

DO - 10.1038/s41598-018-27912-1

M3 - Journal articles

AN - SCOPUS:85048949844

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 9517

ER -

Expression ratio of the TGFβ-inducible gene MYO10 is prognostic for overall survival of squamous cell lung cancer patients and predicts chemotherapy response

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