Survivin in Breast Cancer: A Review

Martínez-Sifuentes, Manuel Antonio; Bassol-Mayagoitia, Susana; Nava-Hernández, Martha P.; Ruíz-Flores, Pablo; Ramos-Treviño, Juan; Cruz, Jorge Haro-Santa; Hernández‐Ibarra, José Anselmo

doi:10.1089/gtmb.2021.0286

Cited by 19 publications

(14 citation statements)

References 107 publications

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“…reported that the BIRC5 mRNA expression was positively correlated with the Gleason score in PCa tissue samples ( 21 ), which validated our findings. The role of BIRC5 in tumor growth and development has also been identified in other cancers, including lung, brain and colon ( 22 – 25 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a prognostic biomarker predicting biochemical recurrence and construction of a novel nomogram for prostate cancer

Chao

et al. 2023

Front. Oncol.

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BackgroundBiochemical recurrence (BCR) is common in prostate cancer (PCa), but its prediction is based predominantly on clinicopathological characteristics with low accuracy. We intend to identify a potential prognostic biomarker related to the BCR and construct a nomogram for improving the risk stratification of PCa patients.MethodsThe transcriptome and clinical data of PCa patients were obtained from TCGA and GEO databases. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to screen out differentially expressed genes (DEGs) related to the BCR of PCa. Cox regression analysis was further applied to screen out DEGs related to BCR-free survival (BFS). Time-dependent receiver operating curve (ROC) analysis and Kaplan–Meier (K-M) survival analysis were conducted to assess the prognostic value. Then, a prognostic nomogram was established and evaluated. The clinicopathological correlation analysis, GSEA analysis, and immune analysis were used to explore the biological and clinical significance of the biomarker. Finally, the qRT-PCR, western blotting, and immunohistochemistry (IHC) were conducted to validate the expression of the biomarker.ResultsBIRC5 was identified to be the potential prognostic biomarker. The clinical correlation analysis and K-M survival analysis found that the BIRC5 mRNA expression was positively associated with disease progression and negatively associated with the BFS rate. Time-dependent ROC curves verified its accurate prediction performance. The GSEA and immune analysis suggested that the BIRC5 was related to immunity. A nomogram with an accurate prediction for BFS of PCa patients was constructed. qRT-PCR, western blotting, and IHC results validated the expression level of BIRC5 in PCa cells and tissues.ConclusionOur study identified BIRC5 as a potential prognostic biomarker related to BCR of PCa and constructed an efficacy nomogram for predicting BFS to assist clinical decision-making.

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Section: Discussionmentioning

confidence: 99%

Identification of a prognostic biomarker predicting biochemical recurrence and construction of a novel nomogram for prostate cancer

Chao

et al. 2023

Front. Oncol.

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“…SOX2 is an oncogene in all breast cancer subtypes [ 59 ] and its expression correlates with breast cancer aggressiveness [ 59 ]. High activity of BIRC5 has been associated with a poor prognosis and worse survival rates in breast cancer patients [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 dependent modulation of Hippo pathway in cancer cells

D’Aguanno,

Brignone,

Scalera

et al. 2024

Cell Commun Signal

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Introduction Bcl-2 and Bcl-xL are the most studied anti-apoptotic members of Bcl-2 family proteins. We previously characterized both of them, not only for their role in regulating apoptosis and resistance to therapy in cancer cells, but also for their non-canonical functions, mainly including promotion of cancer progression, metastatization, angiogenesis, and involvement in the crosstalk among cancer cells and components of the tumor microenvironment. Our goal was to identify transcriptional signature and novel cellular pathways specifically modulated by Bcl-2. Methods We performed RNAseq analysis of siRNA-mediated transient knockdown of Bcl-2 or Bcl-xL in human melanoma cells and gene ontology analysis to identify a specific Bcl-2 transcriptional signature. Expression of genes modulated by Bcl-2 and associated to Hippo pathway were validated in human melanoma, breast adenocarcinoma and non-small cell lung cancer cell lines by qRT-PCR. Western blotting analysis were performed to analyse protein expression of upstream regulators of YAP and in relation to different level of Bcl-2 protein. The effects of YAP silencing in Bcl-2 overexpressing cancer cells were evaluated in migration and cell viability assays in relation to different stiffness conditions. In vitro wound healing assays and co-cultures were used to evaluate cancer-specific Bcl-2 ability to activate fibroblasts. Results We demonstrated the Bcl-2-dependent modulation of Hippo Pathway in cancer cell lines from different tumor types by acting on upstream YAP regulators. YAP inhibition abolished the ability of Bcl-2 to increase tumor cell migration and proliferation on high stiffness condition of culture, to stimulate in vitro fibroblasts migration and to induce fibroblasts activation. Conclusions We discovered that Bcl-2 regulates the Hippo pathway in different tumor types, promoting cell migration, adaptation to higher stiffness culture condition and fibroblast activation. Our data indicate that Bcl-2 inhibitors should be further investigated to counteract cancer-promoting mechanisms.

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“…Briefly, the most prevalent survivin isoform detected in the DCIS tissue analyzed in this study was the wild-type survivin isoform (BIRC5-202). This is the canonical form of survivin and is the most extensively studied isoform found in breast cancer [27,28]. The anti-apoptotic activity of survivin primarily rests in an baculovirus inhibitor of the apoptosis repeat (BIR) domain, thought to bind to cell death, thus promoting caspases directly and/or stabilizing other caspase inhibitors [29].…”

Section: Discussionmentioning

confidence: 99%

Survivin Expression in Luminal Breast Cancer and Adjacent Normal Tissue for Immuno-Oncology Applications

Wright,

Burkholz,

Zelinsky

et al. 2023

IJMS

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Survivin (BIRC5) is a tumor-associated antigen (TAA) overexpressed in various tumors but present at low to undetectable levels in normal tissue. Survivin is known to have a high expression in breast cancer (e.g., Ductal Carcinoma in situ (DCIS) and triple negative breast cancer). Previous studies have not compared survivin expression levels in DCIS tumor samples to levels in adjacent, normal breast tissue from the same patient. To ensure the effective use of survivin as a target for T cell immunotherapy of breast cancer, it is essential to ascertain the varying levels of survivin expression between DCIS tumor tissue samples and the adjacent normal breast tissue taken from the same patient simultaneously. Next-generation sequencing of RNA (RNA-seq) in normal breast tissue and tumor breast tissue from five women presenting with DCIS for lumpectomy was used to identify sequence variation and expression levels of survivin. The identity of both tumor and adjacent normal tissue samples were corroborated by histopathology. Survivin was overexpressed in human breast tissue tumor samples relative to the corresponding adjacent human normal breast tissue. Wild-type survivin transcripts were the predominant species identified in all tumor tissue sequenced. This study demonstrates upregulated expression of wild type survivin in DCIS tumor tissue versus normal breast tissue taken from the same patient at the same time, and provides evidence that developing selective cytotoxic T lymphocyte (CTL) immunotherapy for DCIS targeting survivin warrants further study.

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Survivin in Breast Cancer: A Review

Cited by 19 publications

References 107 publications

Identification of a prognostic biomarker predicting biochemical recurrence and construction of a novel nomogram for prostate cancer

Identification of a prognostic biomarker predicting biochemical recurrence and construction of a novel nomogram for prostate cancer

Bcl-2 dependent modulation of Hippo pathway in cancer cells

Survivin Expression in Luminal Breast Cancer and Adjacent Normal Tissue for Immuno-Oncology Applications

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