RMI2 plays crucial roles in growth and metastasis of lung cancer

Zhan, Weixiang; Liu, Yina; Gao, Ying; Gong, Run; Wang, Wen; Zhang, Ruhua; Wu, Yuanzhong; Kang, Tiebang; Wei, Denghui

doi:10.1038/s41392-020-00295-4

Cited by 15 publications

(16 citation statements)

References 5 publications

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“…RMI2 is an important component of the BLM-TopoIIIa-RMI1-RMI2 complex, which helps to keep the genome stable [ 25 ]. RMI2 expression was linked to a poor prognosis and shorter survival time in patients with hepatocellular cancer [ 26 ] and is also important for lung cancer metastasis and growth [ 27 ]. SWI5 facilitates the Rad51-dependent recombination repair cascade and is a component of the SWI5-SFR1 heterodimers [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

DNA Damage Response Genes in Osteosarcoma

Tang

Liu

Huang

et al. 2021

Journal of Oncology

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Background. Improving the osteosarcoma (OS) patients’ survival has long been a challenge, even though the disease’s treatment is on the verge of progress. DNA damage response (DDR) has traditionally been associated with carcinogenesis, tumor growth, and genomic instability. No study has used DDR genes as a signature to identify the prognosis of OS. The goal of this work was to find an effective possible DDR gene biomarker for predicting OS prognosis, which may be useful in clinical diagnosis and therapy. Methods. To assess gene methylation, univariate and multivariate cox regression analyses were performed on data from OS patients. The data were retrieved from public databases, including the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and the Gene Expression Omnibus (GEO). Results. The DDR gene signature was chosen, which included seven genes (NHEJ1, RMI2, SWI5, ERCC2, CLK2, POLG, and MLH1). In the TARGET dataset, patients were categorized into two groups: high-risk and low-risk. Patients with a high-risk score revealed a shorter OS rate (hazard ratio (HR): 3.15, 95% confidence interval (CI): 1.38–4.34, P < 0.001 ) in comparison with the patients with a low-risk score in the TARGET as a training group. The validation of the prognostic signature accuracy was carried out in relapse and validation cohorts (TARGET, n = 75; GSE21257, n = 53). The signature was found to be an independent predictive factor for OS in multivariate cox regression analysis, and a nomogram model was developed to predict an individual’s risk of OS. DDR gene signature involved in Fanconi anemia pathway, nonhomologous end−joining pathway, mismatch repair, and nucleotide excision repair pathway. Conclusions. Our study suggests that the identified novel DDR genes could be a powerful prognostic tool for prognosis evaluation and a valuable tool in predicting the risk factors in OS patients.

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Section: Discussionmentioning

confidence: 99%

DNA Damage Response Genes in Osteosarcoma

Tang

Liu

Huang

et al. 2021

Journal of Oncology

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“…RMI2 is widely considered to play a crucial role in DNA damage repair. High expression of RMI2 was confirmed to be associated with the worse prognosis in pancreatic cancer ( Xu et al, 2018 ) and lung cancer ( Zhan et al, 2020 ). RMI2 was also reported to act as a tumor promoter by mediating MYCN/PARP DDR signaling pathway in neuroendocrine prostate cancer ( Zhang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 96%

Screening of DNA Damage Repair Genes Involved in the Prognosis of Triple-Negative Breast Cancer Patients Based on Bioinformatics

Wang

Chi

et al. 2021

Front. Genet.

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Background: Triple-negative breast cancer (TNBC) is a special subtype of breast cancer with poor prognosis. DNA damage response (DDR) is one of the hallmarks of this cancer. However, the association of DDR genes with the prognosis of TNBC is still unclear.Methods: We identified differentially expressed genes (DEGs) between normal and TNBC samples from The Cancer Genome Atlas (TCGA). DDR genes were obtained from the Molecular Signatures Database through six DDR gene sets. After the expression of six differential genes were verified by quantitative real-time polymerase chain reaction (qRT-PCR), we then overlapped the DEGs with DDR genes. Based on univariate and LASSO Cox regression analyses, a prognostic model was constructed to predict overall survival (OS). Kaplan–Meier analysis and receiver operating characteristic curve were used to assess the performance of the prognostic model. Cox regression analysis was applied to identify independent prognostic factors in TNBC. The Human Protein Atlas was used to study the immunohistochemical data of six DEGs. The prognostic model was validated using an independent dataset. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were performed by using gene set enrichment analysis (GSEA). Single-sample gene set enrichment analysis was employed to estimate immune cells related to this prognostic model. Finally, we constructed a transcriptional factor (TF) network and a competing endogenous RNA regulatory network.Results: Twenty-three differentially expressed DDR genes were detected between TNBC and normal samples. The six-gene prognostic model we developed was shown to be related to OS in TNBC using univariate and LASSO Cox regression analyses. All the six DEGs were identified as significantly up-regulated in the tumor samples compared to the normal samples in qRT-PCR. The GSEA analysis indicated that the genes in the high-risk group were mainly correlated with leukocyte migration, cytokine interaction, oxidative phosphorylation, autoimmune diseases, and coagulation cascade. The mutation data revealed the mutated genes were different. The gene-TF regulatory network showed that Replication Factor C subunit 4 occupied the dominant position.Conclusion: We identified six gene markers related to DDR, which can predict prognosis and serve as an independent biomarker for TNBC patients.

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“…Moreover, it is overexpressed in IDC followed by LC [ 84 ]. RMI2 is also upregulated in breast cancer [ 85 ] and SNPs in BLM and RMI1 were associated with breast carcinoma [ 86 ]. Controversially, BLM was reported to be overexpressed in aggressive clinicopathological breast cancer phenotypes, and also reported to be downregulated in other breast cancer subtypes.…”

Section: Discussionmentioning

confidence: 99%

The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine

et al. 2021

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In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients’ response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients’ samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients’ samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients’ samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.

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RMI2 plays crucial roles in growth and metastasis of lung cancer

Cited by 15 publications

References 5 publications

DNA Damage Response Genes in Osteosarcoma

DNA Damage Response Genes in Osteosarcoma

Screening of DNA Damage Repair Genes Involved in the Prognosis of Triple-Negative Breast Cancer Patients Based on Bioinformatics

The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine

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