Circulating Noncoding RNAs in Pituitary Neuroendocrine Tumors-Two Sides of the Same Coin

Pituitary neuroendocrine tumors (PitNET) are common intracranial neoplasms. While in case of hormone secreting tumors pituitary hormone measurements can be used for monitoring the disease, in non-functional tumors there is a need to discover non-invasive biomarkers. Non-coding RNAs (ncRNAs) are popular biomarker candidates due to their stability and tissue specificity. Among ncRNAs, miRNAs, lncRNAs and circRNAs have been investigated the most in pituitary tumor tissues and in circulation. However, it is still not known whether ncRNAs are originated from the pituitary, or whether they are casually involved in the pathophysiology. Additionally, there is strong diversity among different studies reporting ncRNAs in PitNET. Therefore, to provide an overview of the discrepancies between published studies and to uncover the reasons why despite encouraging experimental data application of ncRNAs in clinical routine has not yet taken hold, in this review available data are summarized on circulating ncRNAs in PitNET. The data on circulating miRNAs, lncRNAs and circRNAs are organized according to different PitNET subtypes. Biological (physiological and pathophysiological) factors behind intra- and interindividual variability and technical aspects of detecting these markers, including preanalytical and analytical parameters, sample acquisition (venipuncture) and type, storage, nucleic acid extraction, quantification and normalization, which reveal the two sides of the same coin are discussed.