Unique circulating microRNA profiles in epidemic Kaposi's sarcoma

Non-coding RNA Research

Nixon Niyonzima¹  Hassan Kasujja²  Freddie Bwanga³  Carolyne Atugonza⁴  Sembajwe Larry Fred⁴  Ali Moses Damani⁴  Faith Nakazzi⁴  Haruna Muwonge⁴  Robert Zavuga⁴  Ivan Kimuli⁴  Joshua Nfambi⁴  Damalie Nakanjako⁵  Allan Lugaajju⁵  David Patrick Kateete⁵  Josephine Kasolo⁶  Edgar Kigozi⁷ 

[1] Corresponding author. Department of Physiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P. O Box 7072, Kampala, Uganda.;Habib Medical School, Islamic University in Uganda (IUIU), Uganda;Department of Medicine, School of Medicine, Makerere University College of Health Sciences, P. O Box 7072, Kampala, Uganda;Department of Physiology, School of Biomedical Sciences, Makerere University College of Health Sciences, P. O Box 7072, Kampala, Uganda;Medical and Molecular Laboratories, Makerere University College of Health Sciences, P. O Box 7072, Kampala, Uganda;Uganda Cancer Institute (UCI)-Fred Hutch Collaboration, P. O Box 3935, Kampala, Uganda;Uganda Peoples Defence forces (UPDF), P. O Box 123, Bombo, Uganda;

关键词: microRNA;    Circulating microRNA;    Kaposi's sarcoma;    Biomarker;    Blood;    Serum;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS. Methods: This was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data. Results: Fifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. Conclusions: This study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

【 授权许可】

Unknown