Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts

Oparina, N. Yu.; Erlandsson, Malin C.; Beding, Anna Fäldt; Parris, Toshima Z.; Helou, Khalil; Karlsson, Per; Einbeigi, Zakaria; Bokarewa, Maria

doi:10.3390/cancers13092209

Cited by 32 publications

(27 citation statements)

References 68 publications

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“…Recently, a study identified an association between BIRC5 expression and tumor-infiltrating lymphocytes (TILs) [ 6 ]. Moreover, we previously evaluated BIRC5 in breast cancer subtypes, thereby demonstrating that high BIRC5 expression is associated with worse prognosis in breast cancer patients [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

et al. 2022

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Background The BIRC5 gene encodes for the Survivin protein, which is a member of the inhibitor of apoptosis family. Survivin is found in humans during fetal development, but generally not in adult cells thereafter. Previous studies have shown that Survivin is abundant in most cancer cells, thereby making it a promising target for anti-cancer drugs and a potential prognostic tool. Methods To assess genetic alterations and mutations in the BIRC5 gene as well as BIRC5 co-expression with other genes, genomic and transcriptomic data were downloaded via cBioPortal for approximately 9000 samples from The Cancer Genome Atlas (TCGA) representing 33 different cancer types and 11 pan-cancer organ systems, and validated using the ICGC Data Portal and COSMIC. TCGA BIRC5 RNA sequencing data from 33 different cancer types and matching normal tissue samples for 16 cancer types were downloaded from Broad GDAC Firehose and validated using breast cancer microarray data from our previous work and data sets from the GENT2 web-based tool. Survival data were analyzed with multivariable Cox proportional hazards regression analysis and validated using KM plotter for breast-, ovarian-, lung- and gastric cancer. Results Although genetic alterations in BIRC5 were not common in cancer, BIRC5 expression was significantly higher in cancer tissue compared to normal tissue in the 16 different cancer types. For 14/33 cancer types, higher BIRC5 expression was linked to worse overall survival (OS, 4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). Interestingly, higher BIRC5 expression was associated with better OS in lung squamous cell carcinoma and ovarian serous cystadenocarcinoma. Higher BIRC5 expression was also linked to shorter progressive-free interval (PFI) for 14/33 cancer types (4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). External validation showed that high BIRC5 expression was significantly associated with worse OS for breast-, lung-, and gastric cancer. Conclusions Our findings suggest that BIRC5 overexpression is associated with the initiation and progression of several cancer types, and thereby a promising prognostic biomarker.

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Section: Introductionmentioning

confidence: 99%

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

et al. 2022

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“…Many of the SC marker genes are correlated with poor BrC patient survival statistics in the literature. BrCs expressing BIRC5, CENPF, or UBE2C have reduced disease-free, metastasis-free, and overall survival [ 43 , 50 , 52 , 59 , 60 ]. HIST1H4C expression is associated with worse overall and metastasis-free survival in BrCs [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Newly identified breast luminal progenitor and gestational stem cell populations likely give rise to HER2-overexpressing and basal-like breast cancers

McMullen

Soto

2022

Discov Onc

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Breast Cancer (BrC) is a common malignancy with genetically diverse subtypes. There is evidence that specific BrC subtypes originate from particular normal mammary cell populations. However, the cell populations that give rise to most BrC subtypes are unidentified. Several human breast scRNAseq datasets are available. In this research, we utilized a robust human scRNAseq dataset to identify population-specific marker genes and then identified the expression of these marker genes in specific BrC subtypes. In humans, several BrC subtypes, HER2-enriched, basal-like, and triple-negative (TN), are more common in women who have had children. This observation suggests that cell populations that originate during pregnancy give rise to these BrCs. The current human datasets have few normal parous samples, so we supplemented this research with mouse datasets, which contain mammary cells from various developmental stages. This research identified two novel normal breast cell populations that may be the origin of the basal-like and HER2-overexpressing subtypes, respectively. A stem cell-like population, SC, that expresses gestation-specific genes has similar gene expression patterns to basal-like BrCs. A novel luminal progenitor cell population and HER2-overexpressing BrCs are marked by S100A7, S100A8, and S100A9 expression. We bolstered our findings by examining SC gene expression in TN BrC scRNAseq datasets and S100A7-A9 gene expression in BrC cell lines. We discovered that several potential cancer stem cell populations highly express most of the SC genes in TN BrCs and confirmed S100A8 and A9 overexpression in a HER2-overexpressing BrC cell line. In summary, normal SC and the novel luminal progenitor cell population likely give rise to basal-like and HER2-overexpressing BrCs, respectively. Characterizing these normal cell populations may facilitate a better understanding of specific BrCs subtypes.

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“…Baculoviral IAP Repeat Containing 5 (BIRC5) is an apoptotic inhibitor protein (IAP), which has the characteristics of cell cycle-dependent expression and significantly up-regulated expression in the G2/M phase ( 19 ). BIRC5 is believed to inhibit the activity of Caspase-3 and Caspase-7 to impede cell apoptosis and promote cell mitosis and tumor progression ( 20 , 21 ). Also, it is widely considered a potential therapeutic target ( 22 , 23 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the key prognostic genes and potential traditional Chinese medicine therapeutic targets in glioblastoma based on bioinformatics and network pharmacology methods

Xia

Gao

Chen

et al. 2022

Transl Cancer Res TCR

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Background To analyze the key prognostic genes and potential traditional Chinese medicine targets in glioblastoma (GBM) by bioinformatics and network pharmacology. Methods GBM datasets were obtained from the Gene Expression Omnibus (GEO) database to clarify the differentially-expressed genes (DEGs) in the carcinoma and paracancerous tissues. The molecular functions (MF) and signaling pathways of enriched DEGs were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The STRING database and Cytoscape software were used to construct the protein-protein interaction (PPI) network and screen hub genes to focus on genes with greater clinical significance. The transcription expression and prognosis of hub genes were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database. The important compounds and target molecules were obtained via the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. We identified the active ingredients by setting the property values of pharmacokinetic attribute values. We constructed the network of “Chinese medicine ingredients-DEGs target” and screened out the target genes and active ingredients with high correlation scores. Finally, molecular docking verification was carried out using AutoDock Tools and PyMOL. Results We obtained 271 DEGs, including 212 up-regulated genes and 59 down-regulated genes and screened ten hub genes. GO and KEGG analyses suggested that the hub genes were mainly involved in the following biological processes: the cell cycle, cell division, and cell adhesion, as well as extracellular matrix adhesion-related pathways, the p53 signaling pathways, and cadherin binding involved in cell-cell adhesion. We established the interaction network between the components and DEGs to screen out the traditional Chinese medicine active component (luteolin) and target genes (BIRC5 and CCNB1) for the treatment of GBM. The molecular docking results showed that the bindings of protein receptors, BIRC5 and CCNB1, with the compound ligand, luteolin, were stable and formed by hydrogen bonding interaction. Conclusions In this study, we determined that luteolin potentially inhibits glioblastoma proliferation and migration through key target genes, BIRC5 and CCNB1, via bioinformatics and network pharmacology analysis, and affects the prognosis of GBM patients, providing new ideas for clinical targeted therapy and new drug development.

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Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts

Cited by 32 publications

References 68 publications

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

Newly identified breast luminal progenitor and gestational stem cell populations likely give rise to HER2-overexpressing and basal-like breast cancers

Analysis of the key prognostic genes and potential traditional Chinese medicine therapeutic targets in glioblastoma based on bioinformatics and network pharmacology methods

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