RNA-Seq of Kaposi's sarcoma reveal alterations in glucose and lipid metabolism

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS). In sub-Saharan Africa, the high prevalence of both HIV-1 and KSHV has made KS a leading cancer in the region, associated with poor prognosis and high mortality due to late medical presentation and advanced disease stages. A better understanding of the cellular and viral transcriptome profiles during neoplastic growth will aid in the definition of biomarkers and cellular functions associated with KS tumorigenesis and progression. Our approach is to examine the transcriptome profile in actual KS lesions versus non-cancer tissues from the same individual for a total of four male African epidemic KS patients. These patients have undetectable HIV-1 plasma viral load after successful anti-retroviral therapy. Our results capture the cellular complexity of in vivo lesion environment and provide a marked contrast to those derived from in vitro monoculture models. The findings demonstrate that latency and immune modulation related functions dominate the viral gene expression pattern. Moreover, KSHV significantly affected the cellular transcriptome profile with genes involved in lipid and glucose metabolism disorder pathways being the most substantially dysregulated. Despite the implied infiltration of immune cells into the lesions as predicted by CIBERSORT, KS tumor continued to progress, suggesting immunological dysfunction in these KS patients despite control of HIV-1 viremia. Lastly, there is limited overlap of our in vivo dataset with in vitro studies, suggesting a limitation of in vitro KS models. Overall design: RNA-seq of Kaposi's sarcoma lesions and control tissues

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Tso FY, Kossenkov AV, Lidenge SJ, Ngalamika O, Ngowi JR, Mwaiselage J, Wickramasinghe J, Kwon EH, West JT, Lieberman PM, Wood C