Virus host interactions in clinical samples

Division Of Basic Sciences - Nci

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Abstract

Kaposi sarcoma (KS), caused by Kaposi sarcoma herpesvirus (KSHV), is a multicentric tumor characterized by abnormal vasculature and proliferation of KSHV-infected spindle cells. KS involves the skin but can also affect the gastrointestinal tract (GI) in severe cases. Here, we performed RNA sequencing of skin and GI KS lesions from patients with KS to understand the similarities and differences in the gene expression pattern. We obtained skin and GI KS lesions with matched normal skin and GI samples. Differential gene expression was measured by comparing KS lesions to normal matched samples. Twenty-five paired samples were obtained (skin (10 pairs) and GI (15 pairs)) from 23 patients with KS (21 patients had concurrent HIV infection). All tumors were stage T1. Twelve paired samples were from patients who had received prior KS therapy. In skin KS, cellular gene networks associated with cell adhesion (extracellular matrix), immune response, angiogenesis, and hypoxia were dysregulated when compared with normal skin. From samples with higher KSHV sequencing reads, there were 68 human genes increased (2 decreased) in both skin and GI KS lesions. Of these genes those that were clinically significant included FLT4, which encodes for a receptor of VEGF-C and VEGF-D. There were more lytic viral genes detected in GI KS as compared to skin KS, which may be due to more advanced KS or a difference in lytic activation in GI tissues. Some patients shared both skin and GI KS (with matched normal samples), which demonstrated that specific genes were strongly increased in both tissues. This is one of the first studies comparing skin and GI KS that highlights differences in viral gene and clinically relevant host gene expression between these tissues. By analyzing these gene expression patterns, this ongoing study will improve our understanding of KS pathogenesis.