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Concurrent KSHV-associated diseases (KAD), including multicentric Castleman disease, primary effusion lymphoma, and KSHV-associated inflammatory cytokine syndrome may modify KS biology and impact clinical outcomes. Transcriptomic profiling of archival KS tissue enables investigation of molecular heterogeneity associated with these overlapping disease states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Archival formalin-fixed paraffin-embedded (FFPE) KS skin biopsies from 42 patients with HIV-associated KS between 2017 and 2022 were analyzed based on confirmed histopathologic diagnosis, tissue adequacy for RNA profiling, and availability of linked clinical data. Bulk transcriptomic analyses were conducted using Nanostring nCounter PanCancer ImmunoOncology panel supplemented with KSHV-specific probes. Spatial RNA profiling was performed on four tissues from participants with KS and concurrent KAD (KS+KAD) using GeoMx digital spatial profiling (DSP) platform. Regions of interest were selected using LANA-1, CD45 and CD31 staining to characterize tumor (LANA-1+, CD31\n                      <jats:sup>+<\/jats:sup>\n                      ), vessel (LANA-1-negative, CD31\n                      <jats:sup>+<\/jats:sup>\n                      ) and immune cells (CD45\n                      <jats:sup>+<\/jats:sup>\n                      ) areas. For bulk transcriptomic analyses and spatial transcriptomic analyses,\n                      <jats:italic>p<\/jats:italic>\n                      -values were adjusted for multiple comparisons using the Benjamin-Hochberg FDR approach, and adjusted\n                      <jats:italic>p<\/jats:italic>\n                      -values (padj) are reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      KS samples were obtained from 42 men with HIV (median age 40\u2009years). Median HIV viral load of 27 copies\/mL and median CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell count was 211 cells\/\u00b5L. Forty-eight percent had KS alone and 52% had KS+KAD. Patients with KS+KAD had worse survival compared to those with KS alone. Transcriptomic analyses identified increased expression of\n                      <jats:italic>STC1<\/jats:italic>\n                      (log2FC\u2009=\u20092.02, padj\u2009=\u20090.001), a secreted glycoprotein, and\n                      <jats:italic>MKI67<\/jats:italic>\n                      (log2FC\u2009=\u20091.11, padj\u2009=\u20090.02), a common proliferation marker, in KS+KAD lesions, along with lower expression of cytokine-associated pathways. Spatial RNA profiling from 4 KS samples from patients with KS+KAD identified increased abundance of lymphatic endothelial cells, elevated\n                      <jats:italic>LYVE1<\/jats:italic>\n                      expression in LANA-1+ tumor areas as compared to LANA-negative areas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bulk and spatial transcriptomic profiling of archival HIV-associated KS lesions revealed disease-specific molecular programs associated with concurrent KAD that altered tumor and microenvironment features. These findings demonstrate the heterogeneity of HIV-associated KS lesions that may guide future studies on KS pathogenesis and potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-07976-8","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T11:32:40Z","timestamp":1772883160000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial and bulk transcriptomics reveal distinct molecular signatures in Kaposi sarcoma with and without other KSHV-associated diseases"],"prefix":"10.1186","volume":"24","author":[{"given":"Quashawn","family":"Chadwick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ned","family":"Cauley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Mercado-Matos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahman","family":"Afsari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bassel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelly Sampaio","family":"De Melo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Lurain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Yarchoan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Ziegelbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Febres-Aldana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie T.","family":"Krug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5709-4675","authenticated-orcid":false,"given":"Ramya","family":"Ramaswami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"issue":"2","key":"7976_CR1","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1086\/518791","volume":"196","author":"EA Engels","year":"2007","unstructured":"Engels EA, Atkinson JO, Graubard BI, McQuillan GM, Gamache C, Mbisa G, et al. 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Both protocols were approved by the NIH Institutional Review Board. All enrolled participants gave written informed consent in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"A part of this study was presented at the American Society of Clinical Oncology (ASCO) 2025, Chicago, IL and the International Conference on Malignancy in HIV 2024, Bethesda, MD. Data from this material should not be interpreted as representing the viewpoint of the U.S. Department of Health and Human Services, the National Institutes of Health, or the National Cancer Institute.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Prior presentation and publication disclaimer"}},{"value":"R. Yarchoan, R Ramaswami and K Lurain report receiving research support from Celgene (now Bristol Myers Squibb), CTI BioPharma (a Sobi A.B. Company), PDS Biotech, and Janssen Pharmaceuticals through CRADAs with the NCI. R. Yarchoan, R Ramaswami and K Lurain also reports receiving drugs for clinical trials from Merck, EMD-Serano, and Eli Lilly and preclinical material from Lentigen Technology through CRADAs or MTAs with the NCI. T.S. Uldrick reports receiving other commercial research support from Roche through a CTA with Fred Hutchinson Cancer Research Center and is now employed by Regeneron Pharmaceuticals. R. Yarchoan is a co-inventor on US Patent 10,001,483 entitled \u201cMethods for the treatment of Kaposi\u2019s sarcoma or KSHV-induced lymphoma using immunomodulatory compounds, and uses of biomarkers.\u201d R. Yarchoan is also a coinventor on patents on a peptide vaccine for HIV and on the treatment of Kaposi sarcoma with IL12, and an immediate family member of R. Yarchoan is a co-inventor on patents related to internalization of target receptors, on KSHV viral IL-6, and on the use of calreticulin and calreticulin fragments to inhibit angiogenesis. All rights, title, and interest to these patents have been or should by law be assigned to the U.S. Department of Health and Human Services; the government conveys a portion of the royalties it receives to its employee inventors under the Federal Technology Transfer Act of 1986 (P.L. 99\u2013502). No potential conflicts of interest were disclosed by the other authors.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests and COI disclosures"}}],"article-number":"508"}}