Evidence for Tumour Suppressor Function of DOK7 in Human Breast Cancer

Bracken, James; Ghanem, Tamara; Kasem, Abdul; Jiang, Wei; Mokbel, Kefah

doi:10.4236/jct.2014.51009

Cited by 6 publications

(3 citation statements)

References 53 publications

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“…Several studies suggested DOK7 as a potential tumor-suppressor gene, because of the significantly low expression levels in BC tissues compared with normal tissues. The lower expression level of DOK7 was associated with the greater aggressive clinical behaviors and poorer prognosis in BC 47 . The mechanistic studies by Yue et al 48 illustrated that DOK7 inhibited proliferation and invasion of BC cells through PI3K/PTEN/AKT pathway.…”

Section: Discussionmentioning

confidence: 93%

Identification of an exosome-related signature associated with prognosis and immune infiltration in breast cancer

Guo,

Pan,

Qiu

et al. 2023

Sci Rep

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Exosomes, nanosized vesicles, play a vital role in breast cancer (BC) occurrence, development, and drug resistance. Hence, we proceeded to study the potential prognostic value of exosome-related genes and their relationship to the immune microenvironment in BC. 121 exosome-related genes were provided by the ExoBCD database, and 7 final genes were selected to construct the prognostic signature. Besides, the expression levels of the 7 exosome-related genes were validated by the experiment in BC cell lines. Based on the signature, BC patients from the training and validation cohorts were separated into low- and high-risk groups. Subsequently, the R clusterProfiler package was applied to identify the distinct enrichment pathways between high-risk groups and low-risk groups. The relevance of the tumor immune microenvironment and exosome-related gene risk score were analyzed in BC. Eventually, the different expression levels of immune checkpoint-related genes were compared between the two risk groups. Based on the risk model, the low-risk groups were identified with a higher survival rate both in the training and validation cohorts. A better overall survival was revealed in patients with higher scores evaluated by the estimation of stromal and immune cells in malignant tumor tissues using expression (ESTIMATE) algorithm. Subsequently, BC patients with lower risk scores were indicated by higher expression levels of some immune checkpoint-related genes and immune cell infiltration. Exosomes are closely associated with the prognosis and immune cell infiltration of BC. These findings may contribute to improving immunotherapy and provide a new vision for BC treatment strategies.

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Section: Discussionmentioning

confidence: 93%

Identification of an exosome-related signature associated with prognosis and immune infiltration in breast cancer

Guo,

Pan,

Qiu

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Several studies suggested DOK7 as a potential tumor-suppressor gene, because of the signi cantly low expression levels in BC tissues compared with normal tissues. The lower expression level of DOK7 was associated with the greater aggressive clinical behaviors and poorer prognosis in BC [45]. The mechanistic studies by Yue et al illustrated that DOK7 inhibited proliferation and invasion of BC cells through PI3K/PTEN/AKT pathway [46].…”

Section: Discussionmentioning

confidence: 99%

Identification of an Exosome-Related Signature Associated with Prognosis and Immune Infiltration in Breast Cancer

Guo

Qiu

Pan

et al. 2022

Preprint

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Background: Exosomes are nanosized vesicles, play a vital role in breast cancer (BC) occurrence, development, invasion, metastasis, and drug resistance. Nevertheless, studies about exosome-related genes in breast cancer are limited. Besides, the interaction between the exosomes and tumor immune microenvironment (TIME) in BC are still unclear. Hence, we procced to study the potential prognostic value of exosome-related genes and their relationship to immune microenvironment in BC. Methods: 121 exosome-related genes were provided by ExoBCD database and 7 final genes were selected from the intersection of 33 differential expression genes (DEGs) and 19 prognostic genes in BC. Based on the expression levels of the 7 genes, downloaded from The Cancer Genome Atlas (TCGA) database, as well as the regression coefficients, the exosome-related signature was constructed. As a result, the patients in TCGA and GEO database were separated into low- and high- risk groups, respectively. Subsequently, R clusterProfiler package was applied to identify the distinct enrichment pathways between high-risk group and low-risk group. The ESTIMATE method was used to calculate ESTIMATE Score and CIBERSORT was applied to evaluate the immune cell infiltration. Eventually, the different expression levels of immune checkpoint related genes were analyzed between the two risk groups. Results: Results of BC prognosis vary from different risk groups. The low-risk groups were identified with higher survival rate both in TCGA and GEO cohort. The DEGs between high- and low- risk groups were found to enrich in immunity, biological processes, and inflammation pathways. The BC patients with higher ESTIMATE scores were revealed to have better overall survival (OS). Subsequently, CD8+ T cells, naive B cells, CD4+ resting memory T cells, monocytes, and neutrophils were upregulated, while M0 macrophages and M2 macrophages were downregulated in the low-risk group. At last, 4 genes reported as the targets of immune checkpoint inhibitors were further analyzed. The low-risk groups in TCGA and GEO cohorts were indicated with higher expression levels of LAG-3, CD274, TIGIT and CTLA-4. Conclusion: According to this study, exosomes are closely associated with the prognosis and immune cell infiltration of BC patients. These findings may make contributions to improve immunotherapy and bring a new sight for BC treatment strategies.

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“…A recent study of identical twins with differential breast cancer statuses identified DOK7 gene methylation as an indicator of breast cancer risk [ 20 ]. Increased expression of DOK7 has been correlated with longer patient survival time, and decreased expression of the gene has been seen in patients with recurrent cancers [ 21 ]. To our knowledge, a role of DOK7 in tamoxifen resistance has not been previously studied.…”

Section: Introductionmentioning

confidence: 99%

ELF5 and DOK7 regulation in anti-estrogen treated cells and tumors

et al. 2016

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Background Most women with primary breast cancers that express estrogen receptor alpha (ER or ESR1) are treated with endocrine therapies including the anti-estrogen tamoxifen, but resistance to these anti-endocrine therapies often develops. This study characterizes the expression of hormone receptors, and the mRNA and DNA methylation levels of docking protein 7 (DOK7), and E74-like factor 5 (ELF5), in 21 novel tamoxifen-resistant cell lines and extends the findings to primary and recurrent human breast tumors. MethodsTwenty-one tamoxifen-selected cell lines were developed through cloning by limiting dilution of an MCF-7 cell culture treated with 1 μM tamoxifen for 6 months. The parent (MCF-7) and tamoxifen-selected cell lines were characterized for protein expression of ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) using immunohistochemistry (IHC). The mRNA levels of ER, DOK7, and ELF5 were assessed using quantitative RT-PCR. Promoter methylation levels of DOK7 and ELF5 were determined by pyrosequencing of bisulfite-modified DNA. The relationship between hormone receptor status and promoter methylation of DOK7 and ELF5 was further examined using available methylation array data (Illumina HM450) from a set of paired primary and second breast tumors from 24 women.ResultsAll 21 of the novel tamoxifen-selected cell lines are ER-positive, and HER2-negative, and 18 of the cell lines are PR-negative while the MCF-7 cells were scored as ER-positive, modestly PR-positive and HER2 negative. Expression of DOK7 and ELF5 is significantly up-regulated in half of the tamoxifen-selected cell lines as compared to the parental MCF-7. In contrast, the previously established ER-negative TMX2-28 cell line has decreased expression of both DOK7 and ELF5 and increased DNA methylation in the transcriptional start site region of these genes. ELF5 methylation was lower in second versus primary tumors in women who received anti-estrogen treatment, in PR-negative versus PR-positive tumors, and in the subset of PR-positive first tumors from the group of women who had second PR-negative tumors as compared to those who had second PR-positive tumors.ConclusionsThe distinct ELF5 methylation of PR-positive primary tumors from women who had a PR-negative recurrence indicates the possibility of stratification of women for tailored treatment in the early stages of disease.

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Evidence for Tumour Suppressor Function of DOK7 in Human Breast Cancer

Cited by 6 publications

References 53 publications

Identification of an exosome-related signature associated with prognosis and immune infiltration in breast cancer

Identification of an exosome-related signature associated with prognosis and immune infiltration in breast cancer

Identification of an Exosome-Related Signature Associated with Prognosis and Immune Infiltration in Breast Cancer

ELF5 and DOK7 regulation in anti-estrogen treated cells and tumors

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