{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:24:42Z","timestamp":1786944282343,"version":"build-2736575974"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Accessible biomarkers are needed to complement conventional clinicopathological risk assessment in endometrial cancer. Calreticulin (CALR) and heat shock protein 70 (HSP70) are stress-related proteins involved in immunogenic cell death and tumor\u2013immune interactions, but their clinicopathological and prognostic relevance remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>This retrospective cohort included 286 surgically treated patients who underwent surgery between January 2016 and December 2023, with administrative follow-up through December 31, 2025. CALR and HSP70 expression was assessed by immunohistochemistry and classified as low or high using prespecified semiquantitative thresholds. CD8+ and CD68+ cell densities were evaluated as immune infiltration markers. Associations with adverse pathological features were examined using logistic regression with false-discovery rate correction. Recurrence-free survival (RFS), defined as recurrence or death, and overall survival (OS) were analyzed using Kaplan-Meier curves and Cox regression. Clinical and integrated models were compared for 3-year recurrence prediction with bootstrap validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>High CALR and high HSP70 expression were independently associated with grade 3 disease, deep myometrial invasion, lymphovascular space invasion, lymph node metastasis, advanced clinicopathological stage, and a secondary adverse pathology summary endpoint after false-discovery rate correction. High expression of either marker was associated with lower CD8+ and higher CD68+ density. In multivariable RFS models including adjuvant treatment, HSP70-high expression remained associated with poorer RFS (adjusted HR 1.85, 95% CI 1.23\u20132.79; P\u00a0=\u00a00.003), whereas CALR-high expression did not. The CALR-high\/HSP70-high phenotype was also associated with poorer RFS (adjusted HR 2.30, 95% CI 1.36\u20133.88; P\u00a0=\u00a00.002). OS models were exploratory because of limited deaths, although associations for HSP70-high expression and the double-high phenotype were directionally consistent. For 3-year recurrence prediction, the integrated model showed a small apparent AUC increase over the clinical model (0.779 vs. 0.763; DeLong P\u00a0=\u00a00.350), which was not retained after bootstrap optimism correction (0.717 vs. 0.720).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>CALR and HSP70 expression were associated with aggressive pathology and an immune profile characterized by reduced CD8+ and increased CD68+ infiltration. HSP70 and the CALR-high\/HSP70-high phenotype showed the most consistent RFS associations, whereas OS and prediction-model findings require cautious interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1884530","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:36:18Z","timestamp":1786941378000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Calreticulin and heat shock protein 70 expression, immune infiltration, and prognostic stratification in endometrial cancer: a retrospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Xueqin","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanzhe","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Third People\u2019s Hospital of Chengdu","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2016.69.4638","article-title":"Addressing the role of obesity in 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