Yoel G Montoyo-Pujol, José J Ponce, Silvia Delgado-García, Tina A Martín, Hortensia Ballester, Elena Castellón-Molla, Angela Ramos-Montoya, Inmaculada Lozano-Cubo, J Miguel Sempere-Ortells, Gloria Peiró
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引用次数: 0
Abstract
Background: Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death worldwide. This heterogeneous disease has been historically considered a non-immunogenic type of cancer. However, recent advances in immunotherapy have increased the interest in knowing the role of the immune checkpoints (IC) and other immune regulation pathways in this neoplasia.
Methods: In this retrospective study, we evaluated the correlation of mRNA expression of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FOXO1 with clinicopathological factors and BC patient's outcome by real-time quantitative polymerase chain reaction (qPCR).
Results: Our results showed that immunoregulatory gene expression depends on BC immunophenotype being CTLA-4 and PDCD1 (PD1) overexpressed on triple-negative/basal-like (TN/BL) and luminal B/HER2-positive phenotypes, respectively, and CD276 (B7-H3), JAK2 and FOXO1 associated with both luminal A and luminal B/HER2-negative tumors. In addition, we found that these genes can also be related to aggressive and non-aggressive clinicopathological characteristics in BC. Finally, survival analysis showed that CTLA-4 expression levels emerge as a significant independent factor of good prognosis in BC patients, especially in the HER2-enriched subtype.
Conclusion: Considering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.
背景：乳腺癌（BC）是女性最常见的癌症，也是全球癌症相关死亡的主要原因。这种异质性疾病历来被认为是一种非免疫原性癌症。然而，免疫疗法的最新进展增加了人们了解免疫检查点（IC）和其他免疫调节途径在这种肿瘤中的作用的兴趣：在这项回顾性研究中，我们通过实时定量聚合酶链反应（qPCR）评估了CTLA-4、PDCD1（PD1）、CD274（PD-L1）、PDCD1LG2（PD-L2）、CD276（B7-H3）、JAK2和FOXO1的mRNA表达与临床病理因素和BC患者预后的相关性：结果表明，免疫调节基因的表达取决于BC免疫表型，CTLA-4和PDCD1（PD1）分别在三阴性/基底样（TN/BL）和管腔B/HER2阳性表型中过表达，而CD276（B7-H3）、JAK2和FOXO1与管腔A和管腔B/HER2阴性肿瘤相关。此外，我们还发现这些基因还与 BC 的侵袭性和非侵袭性临床病理特征有关。最后，生存分析表明，CTLA-4表达水平是BC患者预后良好的重要独立因素，尤其是在HER2富集亚型中：综合上述数据，我们可以得出结论：免疫调节基因的表达取决于肿瘤表型，对BC患者具有潜在的临床意义。
期刊介绍：
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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