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A long noncoding RNA–microRNA expression signature predicts metastatic signature in pheochromocytomas and paragangliomas

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Abstract

Purpose

In hopes of discovering new markers for metastatic or aggressive phenotypes of pheochromocytomas and paragangliomas (PCPG), we analyzed the noncoding transcriptome from patient gene expression data in The Cancer Genome Atlas.

Methods

Differential expression of miRNAs was observed between PCPG molecular subtypes. We specifically characterized candidate miRNAs that are upregulated in pseudohypoxic PCPGs with mutations in succinate dehydrogenase complex subunits, B and/or D (SDHB and/or SDHD, respectively), which are mutations associated with unfavorable clinical outcomes.

Results

Our computational analysis identified four candidate miRNAs that showed elevated expression in metastatic compared to non-metastatic PCPGs: miR-182, miR-183, miR-96, and miR-383. We also found six candidate lncRNAs harboring opposite expression patterns from the miRNAs when we analyzed the expression profiles of their predicted target lncRNAs. Three of these lncRNA candidates, USP3-AS1, LINC00877, and AC009312.1, were validated to have reduced expression in metastatic compared to non-metastatic PCPGs. Finally, using univariate and multivariate analysis, we found miRNA miR-182 to be an independent predictor of metastasis-free survival in PCPGs.

Conclusions

We identified candidate miRNA and lncRNAs associated with metastasis-free survival in PCPGs.

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Data availability

The data used in this paper are available from The Cancer Genome Atlas at the Genomic Data Commons portal: https://gdc.cancer.gov.

Code availability

The R scripts used for this paper are available from https://github.com/suman-ghosal.

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Funding

This research was supported by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Author information

Author notes

  1. These authors contributed equally: Suman Ghosal, Boqun Zhu

Authors and Affiliations

  1. Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA

    Suman Ghosal, Boqun Zhu, Thanh-Truc Huynh, Leah Meuter, Abhishek Jha, Sara Talvacchio, Marianne Knue, Mayank Patel, Tamara Prodanov & Karel Pacak

  2. Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China

    Boqun Zhu

  3. Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Shaoli Das & Uma T. Shankavaram

  4. Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Martha A. Zeiger & Naris Nilubol

  5. Department of Nuclear Medicine, La Timone University Hospital, Aix-Marseille University, Marseille, France

    David Taieb

  6. European Center for Research in Medical Imaging, Aix-Marseille University, Marseille, France

    David Taieb

Authors
  1. Suman Ghosal
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  2. Boqun Zhu
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Contributions

Conception and design: S.G., K.P. Development of methodology: S.G., B.Z. Acquisition of data and experimentation (acquired and managed patients, performed qRT-PCR, etc.): B.Z., T.-T.H., K.P. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): S.G., B.Z. Writing and review of the manuscript: S.G., B.Z., L.M., A.J., S.T., M.K., M.P., T.P., T.-T.H., S.D., M.A.Z., N.N., U.T.S., D.T., K.P. Study supervision: K.P.

Corresponding author

Correspondence to Karel Pacak.

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Ghosal, S., Zhu, B., Huynh, TT. et al. A long noncoding RNA–microRNA expression signature predicts metastatic signature in pheochromocytomas and paragangliomas. Endocrine 75, 244–253 (2022). https://doi.org/10.1007/s12020-021-02857-0

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  • DOI: https://doi.org/10.1007/s12020-021-02857-0

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