Dataset Information

Immune Escape during Breast Tumor Progression.

ABSTRACT: Immunotherapy using checkpoint inhibitors is one of the most promising current cancer treatment strategies. However, in breast cancer, its success has been limited to a subset of patients with triple-negative disease, whose durability of observed responses remain unclear. The lack of detailed understanding of breast tumor immune evasion mechanisms and the treatment of patients with highly heterogeneous metastatic disease contribute to these disappointing results. Here we discuss the current knowledge about immune-related changes during breast tumor progression, with special emphasis on the in situ-to-invasive breast carcinoma transition that may represent a key step of immunoediting in breast cancer. Comprehensive characterization of early-stage disease and better understanding of immunologic drivers of disease progression will likely expand the tools available for immunotherapy and improve patient stratification.

SUBMITTER: Gil Del Alcazar CR

PROVIDER: S-EPMC7138346 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Immune Escape during Breast Tumor Progression.

Gil Del Alcazar Carlos R CR Alečković Maša M Polyak Kornelia K

Cancer immunology research 20200401 4

Immunotherapy using checkpoint inhibitors is one of the most promising current cancer treatment strategies. However, in breast cancer, its success has been limited to a subset of patients with triple-negative disease, whose durability of observed responses remain unclear. The lack of detailed understanding of breast tumor immune evasion mechanisms and the treatment of patients with highly heterogeneous metastatic disease contribute to these disappointing results. Here we discuss the current know ...[more]

PMID: 32238387

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Project description:PurposeInvestigating the role of lncRNAs associated with the latest cell death mode (Disulfideptosis) in renal clear cell carcinoma, as well as their correlation with tumor prognosis, immune escape, immune checkpoints, tumor mutational burden, and malignant tumor progression. Searching for potential biomarkers and targets for renal clear cell carcinoma.MethodsDownloaded the expression profile data and clinical data of 533 cases of renal clear cell carcinoma from the TCGA database, and randomly divided them into a test set (267 cases) and a validation set (266 cases). Based on previous research, 13 genes associated with Disulfideptosis were obtained. Using R software, lncRNAs with a differential expression that is related to the prognosis of renal clear cell carcinoma and associated with Disulfideptosis were screened out. After univariate Cox regression analysis, Lasso regression analysis, and multivariate Cox regression analysis, lncRNAs with independent predictive ability were obtained. A predictive risk model was established based on the risk scores. Verification was carried out between the obtained high-risk and low-risk groups and their subgroups (including Age, Gender, tumor mutational burden (TMB), tumor grading, and staging). Subsequently, a nomogram was established, and a calibration curve was generated for verification. Performed GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) functional enrichment analyses. Downloaded the values of Tumor Immune Dysfunction and Exclusion (TIDE) for all samples and calculated the difference between the high and low-risk groups. Selected human renal tumor cell lines (786-O, OS-RC-2, A-498, ACHN) and human renal cortex proximal tubule epithelial cell line (HK-2). The RNA expression levels of the above lncRNAs in each cell line were analyzed using RT-qPCR (Real-time Quantitative PCR Detecting System). Used siRNA (small interfering RNA) to knock down FAM225B in 786-O and OS-RC-2 cell lines, and then performed in vitro cell experiments to validate the functional characteristics of FAM225B.ResultsOur constructed predictive model includes 5 lncRNAs with an independent predictive ability (FAM225B, ZNF503-AS1, SPINT1-AS1, WWC2-AS2, LINC01338), which can effectively distinguish between patients in high and low-risk groups and their subgroups. The 1, 3, and 5-year AUC (Area Under the ROC Curve) values of the established nomogram are 0.756, 0.752, and 0.781, respectively. The 5-year AUC value is higher compared to other clinical characteristics (Age: 0.598, Gender: 0.488, Grade: 0.680, Stage: 0.717). After the knockdown of FAM225B, the proliferation, migration, and invasion abilities of renal cancer cell lines OS-RC-2 and 786-O all decreased.ConclusionWe have constructed and validated a prognostic model based on Disulfideptosis-associated lncRNAs. This model can effectively predict the high or low risk of patient prognosis and can distinguish the tumor cell mutational burden and immune escape capabilities among high-risk and low-risk patients. This predictive model can serve as an independent prognostic factor for renal clear cell carcinoma, providing a new direction for personalized treatment of patients with renal clear cell carcinoma.

Dataset Information

Immune Escape during Breast Tumor Progression.

Publications

Immune Escape during Breast Tumor Progression.

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