Department of Reproduction and Development, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Environ Toxicol. 2024 May;39(5):2717-2731. doi: 10.1002/tox.24120. Epub 2024 Jan 21.
As a promising immune checkpoint of immunogenic cell death (ICD) and multifunctional calcium-binding 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-tissue expression (GTEx) database. The prognostic value of CALR was analyzed using clinical survival data. Enrichment analysis was conducted using the R package "clusterProfiler." 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-fixed and paraffin-embedded 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-free interval (PFI) and disease-free 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.
作为一种有前途的免疫检查点的免疫原性细胞死亡 (ICD) 和多功能钙结合分子伴侣，钙网蛋白 (CALR) 引起了越来越多的关注。CALR 主要位于细胞内质网中，对乳腺浸润性癌 (BRCA) 的细胞增殖、侵袭、诱导凋亡和血管生成有显著影响。CALR 的过表达可能与预后不良有关。然而，CALR 如何与 BRCA 的免疫浸润和生存预后相关仍不清楚。在这项研究中，我们利用癌症基因组图谱 (TCGA) 和基因型组织表达 (GTEx) 数据库中的 RNAseq 数据研究了 CALR 的表达。利用临床生存数据分析了 CALR 的预后价值。使用 R 包 "clusterProfiler" 进行了富集分析。我们从已发表的文章和在线数据库中下载了 TCGA 样本的免疫细胞浸润评分，并对免疫细胞浸润水平与 CALR 表达之间的相关性进行了分析。我们进一步评估了 CALR 与免疫调节剂之间的关联。此外，我们还评估了 100 例福尔马林固定石蜡包埋的乳腺癌及相邻正常乳腺组织标本中 CALR 的表达。结果发现，CALR 在 BRCA 中高表达，CALR 表达水平在病理分期、T 分期和 N 分期中存在差异。此外，这些结果表明，CALR 的过表达可能对无进展生存期 (PFI) 和无病生存期 (DFS) 产生不利影响，这可能与肿瘤增殖、侵袭和转移有关，导致肿瘤恶化。同时，免疫细胞浸润分析显示，CALR 的表达与中性粒细胞和树突状细胞的数量存在相关性，提示 CALR 与 BRCA 中的许多免疫调节剂高度相关。我们的研究结果为 BRCA 中的 CALR 提供了潜在的生物标志物。CALR 可能与其他免疫调节剂协同作用，调节免疫微环境，这可能被用于开发新的免疫治疗药物。
Cochrane Database Syst Rev. 2018-2-6
Health Technol Assess. 2006-9
Cochrane Database Syst Rev. 2021-4-19
Cochrane Database Syst Rev. 2020-1-9
Zotero 插件