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Different Profiles of Plasma microRNAs in Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism Related to Occult Cancer

1Haemostasis, Thrombosis, Atherosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe, Valencia, Spain, 2Department of Pulmonary Medicine, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); University of Barcelona, Barcelona, Spain, 3Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain, 4Medical-Surgical Unit of Respiratory Diseases, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Seville, Spain, 5Data Science, Biostatistics and Bioinformatics Unit. Medical Research Institute Hospital La Fe, Valencia, Spain

Abstract Number: OC 30.4

Meeting: ISTH 2021 Congress

Theme: Venous Thromboembolism » Cancer Associated Thrombosis

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) and the diagnosis of an occult neoplasm can occur in the follow-up of a pulmonary embolism (PE). Common epigenetic mechanisms might be involved in the pathogenesis of these disorders.

Aims: To study the epigenetic mechanisms in PE and during the PE-follow-up: either CTEPH or cancer through the identification of dysregulated plasma microRNAs (miRs).

Methods: Ten patients with surgical CTEPH, 10 with non-surgical CTEPH; 10 with PE with no diagnosis of either CTEPH or cancer at 2 years-follow-up, 10 PE patients with a diagnosis of occult cancer and 10 healthy subjects were prospectively recruited. Plasma samples were collected. Total plasma RNA was isolated and the expression of 179 miRs was quantified. Expression levels were normalized with the endogenous and stable miR-425-5p selected using BestRef. Statistical analysis of differentially expressed miRs among all groups was performed using R (v3.5.0).

Results: A profile of three plasma miRs was differentially expressed in CTEPH, PE and occult cancer-PE patients: miR-122-5p, miR-125b-5p and miR-365a-3p (Figure 1). Among them, miR-365a-3p and miR-122-5p were downregulated in CTEPH and occult cancer-PE  with respect to PE patients. Moreover, a profile of 3 miRs was able to distinguish the 4 study groups (surgical CTEPH, non-surgical CTPEH, PE and occult cancer-PE): miR-122-5p, miR-1260a and 192-5p (Figure 2). miR-122-5p was especially downregulated in non-surgical CTEPH.

Heatmap of dysregulated plasma miRs in the study groups. Expression level of miR-365a-3p in plasma of the different groups studied.

Conclusions: Two different profiles of plasma miRs might be able to define the patient groups. miR-365a-3p and miR-122-5p are downregulated in CTEPH and occult cancer-PE patients with respect to PE patients which could reveal specific epigenetic mechanisms.
ISCIII-FEDER (PI15/01085, PI15/00582 and CP17/00114), SETH and SEPAR 164/2016.

To cite this abstract in AMA style:

Oto J, Tura-Ceide O, Sánchez-López V, Font C, Osorio J, Bonjoch C, Hervás D, Arellano E, Medina P, Blanco I, Peinado V, Barberà JA, Otero R. Different Profiles of Plasma microRNAs in Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism Related to Occult Cancer [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/different-profiles-of-plasma-micrornas-in-chronic-thromboembolic-pulmonary-hypertension-and-pulmonary-embolism-related-to-occult-cancer/. Accessed September 22, 2023.

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