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Circulating non-coding RNA biomarkers of endocrine tumours

Nature Reviews Endocrinology (2024)Cite this article

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Abstract

Circulating non-coding RNA (ncRNA) molecules are being investigated as biomarkers of malignancy, prognosis and follow-up in several neoplasms, including endocrine tumours of the pituitary, parathyroid, pancreas and adrenal glands. Most of these tumours are classified as neuroendocrine neoplasms (comprised of neuroendocrine tumours and neuroendocrine carcinomas) and include tumours of variable aggressivity. We consider them together here in this Review owing to similarities in their clinical presentation, pathomechanism and genetic background. No preoperative biomarkers of malignancy are available for several forms of these endocrine tumours. Moreover, biomarkers are also needed for the follow-up of tumour progression (especially in hormonally inactive tumours), prognosis and treatment efficacy monitoring. Circulating blood-borne ncRNAs show promising utility as biomarkers. These ncRNAs, including microRNAs, long non-coding RNAs and circular RNAs, are involved in several aspects of gene expression regulation, and their stability and tissue-specific expression could make them ideal biomarkers. However, no circulating ncRNA biomarkers have yet been introduced into routine clinical practice, which is mostly owing to methodological and standardization problems. In this Review, following a brief synopsis of these endocrine tumours and the biology of ncRNAs, the major research findings, pathomechanisms and methodological questions are discussed along with an outlook for future studies.

Key points

  • Endocrine tumours, including pituitary, pancreatic and parathyroid neuroendocrine tumours, adrenocortical cancer and phaeochromocytoma–paraganglioma, share common features in their pathogenesis, genetic background and associated clinical challenges.

  • Non-coding RNAs (ncRNAs) can be exploited as tissue-specific biomarkers of malignancy, prognosis and follow-up, and their circulating counterparts can be measured in blood samples as a form of liquid biopsy.

  • Circulating microRNAs show promising utility as biomarkers of malignancy and prognosis in adrenocortical tumours, and several other differentially expressed ncRNAs were reported in other endocrine tumours.

  • Apart from circulating miR-483-5p and miR-143-3p, few overlaps are observed in the circulating ncRNA molecules expressed from different types of endocrine tumour.

  • None of these biomarkers has yet been introduced into clinical practice, which is mainly owing to difficulties in standardization and methodology.

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Fig. 1: The common genetic background and pathomechanisms of ACC, PPGL, pitNETs, panNETs and parathyroid NETs.
Fig. 2: Biogenesis and secretion of extracellular non-coding RNAs.
Fig. 3: The origin of tumour-associated circulating non-coding RNA.

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Acknowledgements

The authors acknowledge support from the Hungarian National Research, Development and Innovation Office (NKFIH) (grants K134215 and K146906 to P.I. and FK135065 to H.B.), TKP2021-EGA-24 from the National Research, Development and Innovation Fund by the Ministry of Innovation and Technology of Hungary financed under the (TKP2021-EGA) funding scheme. H.B.’s work is supported by the Bolyai Research Fellowship of the Hungarian Academy of Sciences and New National Excellence Program of the Ministry of Human Capacities (UNKP-22-5-SE-1). The National Tumour Biology Laboratory is funded by the Ministry of Innovation and Technology of Hungary (H.B. and A.P.). The authors thank B. Antal (Semmelweis University) for his help with the design of Figs. 2 and 3. B. Antal was supported by the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation.

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Authors and Affiliations

  1. HUN-REN–SU Hereditary Tumours Research Group, Budapest, Hungary

    Henriett Butz & Attila Patócs

  2. Department of Molecular Genetics and the National Tumour Biology Laboratory, National Institute of Oncology, Budapest, Hungary

    Henriett Butz & Attila Patócs

  3. Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Budapest, Hungary

    Henriett Butz & Attila Patócs

  4. Department of Endocrinology, Faculty of Medicine, Semmelweis University, Budapest, Hungary

    Peter Igaz

  5. Department of Internal Medicine and Oncology, Faculty of Medicine, Semmelweis University, Budapest, Hungary

    Peter Igaz

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Butz, H., Patócs, A. & Igaz, P. Circulating non-coding RNA biomarkers of endocrine tumours. Nat Rev Endocrinol (2024). https://doi.org/10.1038/s41574-024-01005-8

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