RAD54B potentiates tumor growth and predicts poor prognosis of patients with luminal A breast cancer

Zhang, Zeyu; Li, Xiaoting; Han, Yingyan; Ji, Tiantian; Huang, Xiaoyuan; Gao, Qinglei; Ma, Ding

doi:10.1016/j.biopha.2019.109341

Cited by 15 publications

(19 citation statements)

References 19 publications

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“…Interestingly, we found that most of HR pathway genes were mainly amplified. The most amplified gene was RAD54B (22.7%, 35/154) which is related to multiple cancers ( 24 – 26 ). However, how RAD54B links to ESCC is unclear.…”

Section: Resultsmentioning

confidence: 99%

“…Similar to the gene mutation profile, HR and NHEJ had a significant gene amplification profile. Previous studies demonstrated that DSB repair pathway genes were over-expressed in cancers and high expression of these genes was associated with cancer development and resistance to chemotherapy and radiotherapy (8,10,11,25,26,47,48). However, how altered DSB repair pathways contribute to ESCC is much less explored.…”

Section: Discussionmentioning

confidence: 99%

“…Contrast to the gene mutation profile, CNVs especially amplification was observed to be the dominant alteration type in DDR pathways. Amplification of DDR pathway genes was reported to play a crucial role in cancer progression ( 9 , 26 , 46 ). We observed that obvious gene amplification occurred in multiple DDR pathways in ESCC.…”

Section: Discussionmentioning

confidence: 99%

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A Comprehensive Analysis of Alterations in DNA Damage Repair Pathways Reveals a Potential Way to Enhance the Radio-Sensitivity of Esophageal Squamous Cell Cancer

et al. 2020

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Esophageal squamous cell cancer (ESCC) is a common malignancy with a poor 5-year overall survival in China. Altered DNA damage repair (DDR) pathways are associated with a predisposition to cancer and contribute to therapeutic response and resistance in cancers. However, alterations of DDR pathway genes in ESCC are still largely unknown. In this study, we employed genome sequencing data of 192 samples, comparative genomic hybridization data of 123 cases, and gene expression microarray data of 119 patients to firstly perform a comprehensive analysis of the gene alterations of 7 DDR pathways in ESCC. Gene mutations and copy number variations (CNVs) were observed in all 7 DDR pathways, and especially, CNVs were the dominant alteration types. Compared with other pathways, two DNA double-strand break (DSB) repair pathways homologous recombination (HR) and nonhomologous end joining (NHEJ), carried significant gene mutations and CNVs especially gene amplifications. Most genes including RAD54B, NBS1, RAD51B, and PRKDC were significantly amplified and over-expressed in ESCC. Amplification and high expression of DSB repair pathway genes were associated with poorer overall survival. Gene set variation analysis further showed that DSB repair pathways were up-regulated in ESCC. Besides, we firstly demonstrated that combination of mirin and NU7441, two inhibitors for HR and NHEJ respectively, with ionizing radiation treatment significantly enhanced DSBs, reduced clonogenic cell survival, inhibited cell proliferation, and promoted cell apoptosis in ESCC cells with DSB pathway gene amplification. These findings suggest that DSB repair pathways were significantly altered in ESCC and inhibiting DSB repair pathways might enhance the radio-sensitivity of ESCC with DSB repair up-regulation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A Comprehensive Analysis of Alterations in DNA Damage Repair Pathways Reveals a Potential Way to Enhance the Radio-Sensitivity of Esophageal Squamous Cell Cancer

et al. 2020

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“…In addition, RAD54B stands for a somatic mutation which is overexpressed in different cancer types including breast cancer. 54,55 In previous reports, the analysis of TA presentation enriched by nanoparticles for the activation of the immune system is rarely reported. [9][10][11] Our nding based on the immunoaffinity separation test supports our hypothesis that tumor antigens enriched by the nanoparticles can be successfully cross presented in the immune cells, which is crucial for the activation of CTLs to induce the antigen specic anti-tumor immunity.…”

Section: Resultsmentioning

confidence: 99%

Post translational modification-assisted cancer immunotherapy for effective breast cancer treatment

et al. 2020

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“…Some important breast cancer and tumor oncogenes, such as PARI, CCNE2 and RAD54B, were detected to have positive correlations with epithelial tissue proportion in our study. Previous studies have demonstrated that PARI overexpression was correlated with aggressive tumor cell proliferation and poor prognosis in breast cancer [24], high expression of CCNE2 in breast cancer is strongly predictive of shorter distant metastasis-free survival following endocrine therapy [25] and RAD54B potentiates tumor growth and predicts poor prognosis of breast cancer patients [26]. The histograms depict the distribution of epithelial tissue proportions, whereas the box plots stratify the cases into low and high epithelial groups using a cutoff = 0.5.…”

Section: Linking Dna Regulatory Elements To Target Genesmentioning

confidence: 99%

Integrative analysis of histopathological images and chromatin accessibility data for estrogen receptor-positive breast cancer

Shao

et al. 2020

BMC Med Genomics

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Background Existing studies have demonstrated that the integrative analysis of histopathological images and genomic data can be used to better understand the onset and progression of many diseases, as well as identify new diagnostic and prognostic biomarkers. However, since the development of pathological phenotypes are influenced by a variety of complex biological processes, complete understanding of the underlying gene regulatory mechanisms for the cell and tissue morphology is still a challenge. In this study, we explored the relationship between the chromatin accessibility changes and the epithelial tissue proportion in histopathological images of estrogen receptor (ER) positive breast cancer. Methods An established whole slide image processing pipeline based on deep learning was used to perform global segmentation of epithelial and stromal tissues. We then used canonical correlation analysis to detect the epithelial tissue proportion-associated regulatory regions. By integrating ATAC-seq data with matched RNA-seq data, we found the potential target genes that associated with these regulatory regions. Then we used these genes to perform the following pathway and survival analysis. Results Using canonical correlation analysis, we detected 436 potential regulatory regions that exhibited significant correlation between quantitative chromatin accessibility changes and the epithelial tissue proportion in tumors from 54 patients (FDR < 0.05). We then found that these 436 regulatory regions were associated with 74 potential target genes. After functional enrichment analysis, we observed that these potential target genes were enriched in cancer-associated pathways. We further demonstrated that using the gene expression signals and the epithelial tissue proportion extracted from this integration framework could stratify patient prognoses more accurately, outperforming predictions based on only omics or image features. Conclusion This integrative analysis is a useful strategy for identifying potential regulatory regions in the human genome that are associated with tumor tissue quantification. This study will enable efficient prioritization of genomic regulatory regions identified by ATAC-seq data for further studies to validate their causal regulatory function. Ultimately, identifying epithelial tissue proportion-associated regulatory regions will further our understanding of the underlying molecular mechanisms of disease and inform the development of potential therapeutic targets.

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RAD54B potentiates tumor growth and predicts poor prognosis of patients with luminal A breast cancer

Cited by 15 publications

References 19 publications

A Comprehensive Analysis of Alterations in DNA Damage Repair Pathways Reveals a Potential Way to Enhance the Radio-Sensitivity of Esophageal Squamous Cell Cancer

A Comprehensive Analysis of Alterations in DNA Damage Repair Pathways Reveals a Potential Way to Enhance the Radio-Sensitivity of Esophageal Squamous Cell Cancer

Post translational modification-assisted cancer immunotherapy for effective breast cancer treatment

Integrative analysis of histopathological images and chromatin accessibility data for estrogen receptor-positive breast cancer

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