CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer

Zhang, Mingdi; Wu, Kangning; Wang, Maoli; Bai, Fang; Chen, Hongliang

doi:10.21203/rs.3.rs-355512/v1

Cited by 2 publications

(1 citation statement)

References 42 publications

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“…A preprint has previously been published [ 51 ]. This work was supported by grants for a clinical research project from the Shanghai Municipal Commission of Health (grant number 20194Y0123, MD Zhang), for a project to foster clinical research from the Obstetrics and Gynecology Hospital of Fudan University (grant number 20017, MD Zhang), for an innovative medical research project under the Scientific and Technological Innovation Action Plan (grant number 20Y11914500, MD Zhang).…”

Section: Acknowledgmentsmentioning

confidence: 99%

CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer

Zhang

Wang

et al. 2022

International Journal of Analytical Chemistry

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Background. Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtypes of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. Material and Methods. Two datasets from gene expression omnibus database (GEO) were selected. Enrichment analysis and protein-protein interaction (PPI) network for the DEGs were performed. We analyzed the prognostic values of hub genes in the Kaplan-Meier Plotter. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) was used to find candidate small molecules capable to reverse the gene status of IBC. Results. 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. The KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A, and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24, and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cancer. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Conclusion. Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC.

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Section: Acknowledgmentsmentioning

confidence: 99%

CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer

Zhang

Wang

et al. 2022

International Journal of Analytical Chemistry

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Meta-analysis of integrated ChIP-seq and transcriptome data revealed genomic regions affected by estrogen receptor alpha in breast cancer

Piryaei,

Salehi,

Ebrahimie

et al. 2023

BMC Med Genomics

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Background The largest group of patients with breast cancer are estrogen receptor-positive (ER+) type. The estrogen receptor acts as a transcription factor and triggers cell proliferation and differentiation. Hence, investigating ER-DNA interaction genomic regions can help identify genes directly regulated by ER and understand the mechanism of ER action in cancer progression. Methods In the present study, we employed a workflow to do a meta-analysis of ChIP-seq data of ER+ cell lines stimulated with 10 nM and 100 nM of E2. All publicly available data sets were re-analyzed with the same platform. Then, the known and unknown batch effects were removed. Finally, the meta-analysis was performed to obtain meta-differentially bound sites in estrogen-treated MCF7 cell lines compared to vehicles (as control). Also, the meta-analysis results were compared with the results of T47D cell lines for more precision. Enrichment analyses were also employed to find the functional importance of common meta-differentially bound sites and associated genes among both cell lines. Results Remarkably, POU5F1B, ZNF662, ZNF442, KIN, ZNF410, and SGSM2 transcription factors were recognized in the meta-analysis but not in individual studies. Enrichment of the meta-differentially bound sites resulted in the candidacy of pathways not previously reported in breast cancer. PCGF2, HNF1B, and ZBED6 transcription factors were also predicted through the enrichment analysis of associated genes. In addition, comparing the meta-analysis results of both ChIP-seq and RNA-seq data showed that many transcription factors affected by ER were up-regulated. Conclusion The meta-analysis of ChIP-seq data of estrogen-treated MCF7 cell line leads to the identification of new binding sites of ER that have not been previously reported. Also, enrichment of the meta-differentially bound sites and their associated genes revealed new terms and pathways involved in the development of breast cancer which should be examined in future in vitro and in vivo studies.

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CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer

Cited by 2 publications

References 42 publications

CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer

CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer

Meta-analysis of integrated ChIP-seq and transcriptome data revealed genomic regions affected by estrogen receptor alpha in breast cancer

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