{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:07:03Z","timestamp":1790140023482,"version":"4.0.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bevacizumab and immune-checkpoint inhibitors (ICIs) improve outcomes in advanced cervical cancer but may cause cardiovascular toxicity (CVT). Public cervical-cancer transcriptomic datasets do not contain cardiac tissue or adjudicated CVT outcomes; consequently, tumour-microenvironment (TME) expression cannot by itself establish a cardiac susceptibility mechanism. We reanalysed the available data to ask the narrower question of whether cervical tissues contain angiogenic, endothelial, inflammatory, T-cell-exhaustion, and TGF-\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \/fibrotic programmes that are biologically relevant to cardio-oncology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>All nine single-cell RNA-sequencing specimens in GSE208653 were analysed: two HPV-negative healthy cervix, two HPV-positive histologically normal cervix, two high-grade squamous intraepithelial lesions, two squamous-cell carcinomas, and one adenocarcinoma. After prespecified quality control, 74,457 cells were integrated with Harmony and annotated into broad lineages. Prespecified module scores and four ligand\u2013receptor expression-product scores were aggregated by biological specimen; malignant versus non-malignant differences were evaluated with exact specimen-label permutation tests and Benjamini\u2013Hochberg correction. Four GSE208654 Visium count matrices were analysed descriptively at spot level. Coexpression among the five programmes was assessed in 304 TCGA-CESC primary tumours. qRT-PCR summary data from HUVEC (ATCC PCS-100-010) and primary human aortic endothelial cells (HAEC; ATCC PCS-100-011) were reinterpreted as endothelial pharmacology, not cardiac validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The scRNA-seq atlas contained 32 clusters spanning epithelial, immune, endothelial, and stromal lineages. None of the five specimen-level programmes differed significantly between malignant and non-malignant specimens after multiple-testing correction (all q\u2009\u2265\u20090.119). Likewise, none of the VEGFA\u2013KDR, IL1B\u2013IL1R1, TGFB1\u2013TGFBR2, or LGALS9\u2013HAVCR2 expression-product scores was significant (all q\u2009\u2265\u20090.143). The four spatial specimens showed heterogeneous spot-level expression but, with one specimen per histology and no slide coordinates in the supplied matrices, did not support group-level spatial inference. TCGA tumours showed coordinated intratumoural expression, strongest between angiogenesis and TGF-\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \/fibrosis (Spearman\n                      <jats:italic>\u03c1<\/jats:italic>\n                      =0.707; q\u2009=\u20092.24\u2009\u00d7\u200910\u207b46), but TCGA-CESC contained no CVT endpoint. VEGFA increased KDR, ICAM1, VCAM1, and EDN1 mRNA in HUVEC, and bevacizumab attenuated these changes; IL-1\n                      <jats:italic>\u03b2<\/jats:italic>\n                      induced inflammatory transcripts in HAEC, and anakinra attenuated IL6, TNF, and CXCL8.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cervical tissues contain cardio-oncology-relevant transcriptional programmes, but the available data neither demonstrate cardiac expression nor identify bevacizumab- or ICI-induced CVT susceptibility. The endothelial experiments show expected pathway responsiveness and pharmacological blockade, not treatment-induced cardiotoxicity. Prospective analyses must compare CVT-positive and CVT-negative treated patients using matched clinical outcomes and, ideally, blood or cardiac-relevant biospecimens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1917892","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:49:37Z","timestamp":1790138977000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardio-oncology-relevant programmes in the cervical cancer tumour microenvironment: an exploratory multi-omics and endothelial-cell study"],"prefix":"10.3389","volume":"13","author":[{"given":"Rongrong","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Gynecology, Nantong Haimen People\u2019s Hospital","place":["Nantong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suqin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of 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