Prognostic and tumor-immune infiltration cell signatures in tamoxifen-resistant breast cancers

Cao, Zhenyu; Jin, Ziwei; Zeng, Liyun; He, Hongyi; Chen, Qitong; Zou, Qiongyan; Ouyang, Dengjie; Luo, Na; Zhang, Yulong; Yuan, Yunchang; Yi, Wei

doi:10.21037/gs-21-566

Cited by 3 publications

(2 citation statements)

References 48 publications

(38 reference statements)

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“…Besides, suppression of SAA1 expression can also occur after surgery or in late cancers. The prognostic value of SAA1 in BC has been frequently reported (Cao et al, 2021;Olivier et al, 2021). Kinesin family member 4A (KIF4A), a KIF protein, is an essential chromosome-associated molecular motor encoding a 140-kDa protein (Cuijpers et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

A Novel Five-Gene Signature Related to Clinical Outcome and Immune Microenvironment in Breast Cancer

Yang

Liu

2022

Front. Genet.

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Breast cancer (BC) is the most frequent cancer in women and the main cause of cancer-related deaths in the globe, according to the World Health Organization. The need for biomarkers that can help predict survival or guide treatment decisions in BC patients is critical in order to provide each patient with an individualized treatment plan due to the wide range of prognoses and therapeutic responses. A reliable prognostic model is essential for determining the best course of treatment for patients. Patients’ clinical and pathological data, as well as their mRNA expression levels at level 3, were gleaned from the TCGA databases. Differentially expressed genes (DEGs) between BC and non-tumor specimens were identified. Tumor immunity analyses have been utilized in order to decipher molecular pathways and their relationship to the immune system. The expressions of KIF4A in BC cells were determined by RT-PCR. To evaluate the involvement of KIF4A in BC cell proliferation, CCK-8 tests were used. In this study, utilizing FC > 4 and p < 0.05, we identified 140 upregulated genes and 513 down-regulated genes. A five-gene signature comprising SFRP1, SAA1, RBP4, KIF4A and COL11A1 was developed for the prediction of overall survivals of BC. Overall survival was distinctly worse for patients in the high-risk group than those in the low-risk group. Cancerous and aggressiveness-related pathways and decreased B cell, T cell CD4+, T cell CD8+, Neutrophil and Myeloid dendritic cells levels were seen in the high-risk group. In addition, we found that KIF4A was highly expressed in BC and its silence resulted in the suppression of the proliferation of BC cells. Taken together, as a possible prognostic factor for BC, the five-gene profile created and verified in this investigation could guide the immunotherapy selection.

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Section: Discussionmentioning

confidence: 99%

A Novel Five-Gene Signature Related to Clinical Outcome and Immune Microenvironment in Breast Cancer

Yang

Liu

2022

Front. Genet.

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“…In BRCA, SAA1 knockdown induces cellular stress and fails to activate the relevant molecular mechanisms involved in DNA as well as underlying biological processes, which may be more favourable for cancer cell survival (56). Another study found that SAA1 overexpression in BRCA may be associated with longer disease-free survival (57). KRT17 can promote carcinogenesis in a variety of cancers (58-60).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis and experimental validation of six cuproptosis-associated genes as prognostic signatures in breast cancer

Chen

Sun

Yang

et al. 2022

Preprint

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Background Breast carcinoma (BRCA) is the life-threatening malignancy in women with poor prognosis. Cuproptosis is a novel mode of cell death, and its relationship with BRCA is unclear. This study endeavored to develop the cuproptosis-relevant prognostic genes and signature for BRCA. Methods Cuproptosis-relevant subtypes of BRCA patients were derived by consistent clustering. Disparate expression analysis was implemented in the ‘limma’ package. The univariate Cox and multivariate Cox analysis were executed to determine the cuproptosis-relevant prognostic signature. The signature was created and affirmed in distinct datasets. The Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) were also conducted to uncover the molecular mechanisms involved in the prognostic signature. ESTIMATE and CIBERSORT algorithm were applied to probe the linkage between the gene signature and tumor microenviroment (TME). Immunotherapy responsiveness were projected by Tumor Immune Dysfunction and Exclusion (TIDE) website. Detection of the expression of cuproptosis-revelant prognostic genes in breast cancer cell lines was implemented by Real Time Quantitative PCR (RT-qPCR). Results A grand total of 38 cuproptosis-associated differentially expressed genes (DEGs) in BRCA were mined by consistent clustering and disparate expression analysis. Based on univariate Cox and multivariate Cox analysis, six cuproptosis-revelant prognostic genes, namely SAA1, KRT17, VAV3, IGHG1, TFF1 and CLEC3A, were mined to establish a cuproptosis-revelant signature. Then, we affirmed the signature by external validation set. GSVA and GSEA manifested that multiple cell cycle-linked and immune-related pathways and biological processes were connected to the signature. The ESTIMATE and CIBERSORT results revealed significantly different TMEs for the two Cusig score subgroups. Finally, the result of RT-qPCR of cell lines further affirmed the expression trend of SAA1, KRT17, IGHG1 and CLEC3A. Conclusion Taken together, this study authenticated the cuproptosis-revelant prognostic genes and developed a signature for the overall survival projection of BRCA, which will provide the basis for developing prognostic molecular biomarkers and in-depth understanding of the relationship between cuproptosis and BRCA.

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Propofol overcome Tamoxifen resistance in breast cancer by modulating tumorogenesis, immune response and metabolism

Yin,

Gao,

Guo

et al. 2024

Preprint

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Although 70% of estrogen receptor (ER)-positive breast cancer patients benefit from Tamoxifen therapy, the developing resistance to Tamoxifen leads to high rates of metastasis and poor prognosis. Propofol, a commonly used anesthetic, has been shown to inhibit the occurrence and development of breast cancer. However, its role in anti-endocrine resistance in ER-positive breast cancer remains unclear. In this study, we found that Propofol significantly promotes cell cycle arrest, induces apoptosis, and inhibits proliferation in Tamoxifen-resistant breast cancer cells. Furthermore, transcriptome sequencing analysis revealed 1065 differentially expressed genes (DEGs) between Propofol-treated Tamoxifen-resistant MCF-7 (MCF7-TR) cells and none-treated MCF7-TR cells. Gene ontology annotation enrichment analysis (GO), Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG), and gene set enrichment analysis (GSEA) showed that Propofol affects the expression of genes located in the plasma membrane and cell periphery, mainly regulating signals involved in cell cycle regulation, immune response modulation, and metabolism. Our results provide new insights into the mechanism by which Propofol controls resistance to Tamoxifen in breast cancer progression and offer a theoretical basis for clinical treatment.

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Prognostic and tumor-immune infiltration cell signatures in tamoxifen-resistant breast cancers

Cited by 3 publications

References 48 publications

A Novel Five-Gene Signature Related to Clinical Outcome and Immune Microenvironment in Breast Cancer

A Novel Five-Gene Signature Related to Clinical Outcome and Immune Microenvironment in Breast Cancer

Bioinformatic analysis and experimental validation of six cuproptosis-associated genes as prognostic signatures in breast cancer

Propofol overcome Tamoxifen resistance in breast cancer by modulating tumorogenesis, immune response and metabolism

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