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To accomplish that, sPD-L2 levels were quantified by enzyme-linked immunosorbent assay and compared between healthy control cats and cats with mammary carcinoma, also stratified by tumor molecular subtype. Statistical associations between sPD-L2 levels, clinicopathological features and other serum immune checkpoint molecules (sPD-1, sPD-L1, sCTLA-4, sTNF-\u03b1, sVEGF-A, sVEGFR-1, sVEGFR-2 and sLAG-3) were also analyzed. Results revealed that sPD-L2 levels were significantly higher in the FMC group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), with a concentration of 1934 pg\/mL established as the best cut-off value to distinguish sick from healthy cats (specificity: 96.6%; sensitivity: 93.6%; AUC\u2009=\u20090.980). Interestingly, cats with HER2-positive or Triple-Negative (TN) mammary carcinoma subtypes showed higher sPD-L2 levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). According to receiver-operating characteristic (ROC) curve analysis, a serum PD-L2 concentration of 5499 pg\/mL represented the optimal cut-off for distinguishing cats with these two subtypes from cats with Luminal A (LA) and Luminal B (LB) carcinomas (specificity: 95.2%; sensitivity: 82.6%; AUC\u2009=\u20090.919). Furthermore, in the FMC group, positive correlations were found between sPD-L2 levels and sCTLA-4 (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.496,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.001), sTNF-\u03b1 (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.482,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0009), sVEGF-A (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.54,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0002), sVEGFR-1 (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.339,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.025), sVEGFR-2 (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.322,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.033) and sLAG-3 levels (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.324,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.032). Finally, significant associations were found between sPD-L2 levels and progesterone receptor (PR) status (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002), HER2 status (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.009) and Ki-67 index (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). A serum sPD-L2 concentration of 3732 pg\/mL was identified as the optimal cut-off value for distinguishing FMCs with a high Ki-67 index (\u2265\u200914%) from those with a low index (specificity: 80.0%; sensitivity: 94.1%; AUC\u2009=\u20090.906). In conclusion, our findings suggest that sPD-L2 is a potential biomarker for FMC, particularly in HER2-positive and TN subtypes.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-41375-9","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T21:06:51Z","timestamp":1771967211000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum programmed death ligand 2 is elevated in cats with mammary carcinoma"],"prefix":"10.1038","volume":"16","author":[{"given":"Vit\u00f3ria Silva","family":"Jo\u00e3o","sequence":"first","affiliation":[]},{"given":"Gon\u00e7alo","family":"Pereira","sequence":"additional","affiliation":[]},{"given":"Gon\u00e7alo","family":"Vicente","sequence":"additional","affiliation":[]},{"given":"Ana Catarina","family":"Urbano","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Correia","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Fernando","family":"Ferreira","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"41375_CR1","doi-asserted-by":"publisher","first-page":"189144","DOI":"10.1016\/j.bbcan.2024.189144","volume":"1879","author":"T Vilela","year":"2024","unstructured":"Vilela, T., Valente, S., Correia, J. & Ferreira, F. 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