{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:56:37Z","timestamp":1786978597546,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,21]],"date-time":"2024-01-21T00:00:00Z","timestamp":1705795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>As a promising immune checkpoint of immunogenic cell death (ICD) and multifunctional calcium\u2010binding molecular chaperone, calreticulin (CALR) has been attracting increasing attention. CALR mainly locates in cellular endoplasmic reticulum and significantly affects cell proliferation, invasion, induction of apoptosis, and angiogenesis in breast invasive carcinoma (BRCA). CALR overexpression might be correlated with a worse outcome. Nonetheless, it remains obscure how CALR correlates with immune infiltration and survival prognosis of BRCA. In this study, we investigated CALR expression utilizing RNAseq data from the cancer genome atlas (TCGA) and genotype\u2010tissue expression (GTEx) database. The prognostic value of CALR was analyzed using clinical survival data. Enrichment analysis was conducted using the R package \u201cclusterProfiler.\u201d We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases and performed a correlation analysis between immune cell infiltration levels and CALR expression. We further assessed the association between CALR and immunomodulators. Moreover, we also evaluated the expression of CALR in 100 formalin\u2010fixed and paraffin\u2010embedded breast cancer and adjacent normal breast tissue specimens. Our results found that CALR was highly expressed in BRCA, and CALR expression levels differed in pathological stages, T stages, and N stages. Besides, these results suggested that CALR overexpression may have adverse effects on the progression\u2010free interval (PFI) and disease\u2010free interval (DFI), which may be related to tumor proliferation, invasion, and metastasis, leading to tumor deterioration. Meanwhile, immune cell infiltration analysis revealed a correlation between the expression of CALR and the number of neutrophils and dendritic cells, suggesting that CALR was highly correlated with many immunomodulators in BRCA. Our results provide potential biomarkers of CALR in BRCA. CALR may interact synergistically with other immunomodulators to regulate the immune microenvironment, which could be utilized to develop new immunotherapy drugs.<\/jats:p>","DOI":"10.1002\/tox.24120","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T02:35:10Z","timestamp":1705890910000},"page":"2717-2731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Calreticulin, a potential coregulator of immune checkpoints and biomarker associated with tumor microenvironment and clinical prognostic significance in breast invasive carcinoma"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6939-0076","authenticated-orcid":false,"given":"Jiali","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Reproduction and Development Obstetrics and Gynecology Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1620-4353","authenticated-orcid":false,"given":"Yiwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Oncology Ruijin Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingdi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery Obstetrics and Gynecology Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21583"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21754"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17414-y"},{"key":"e_1_2_11_5_1","article-title":"Screening for early breast cancer reduces invasive cancer, study finds","volume":"351","author":"Mayor S","year":"2015","journal-title":"BMJ (Clinical Research 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