High expression of DOCK2 indicates good prognosis in acute myeloid leukemia

Hu, Ning; Pang, Yifan; Zhao, Haixia; Si, Chaozeng; Ding, Hui; Chen, Li; Wang, Chao; Qin, Tong; Li, Qianyu; Han, Yu; Dai, Yifeng; Zhang, Yijie; Shi, Jianxin; Wu, Depei; Zhang, Xinyou; Cheng, Zhiheng; Fu, Lin

doi:10.7150/jca.33244

Cited by 13 publications

(13 citation statements)

References 27 publications

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“…It can also regulate the functions of innate immune cells such as the migration and interferon (IFN) secretion of plasmacytoid dendritic cells, the cytotoxicity of natural killer (NK) cells, and the reactive oxygen species (ROS) production of neutrophils ( Chen et al, 2018b ). DOCK2 mutations have been observed in many cancers, including chronic lymphocytic leukemia (CLL), prostate cancer, and acute myeloid leukemia (AML; Hasan et al, 2018 ; Bjerre et al, 2019 ; Hu et al, 2019 ). In particular, DOCK2 might be a potential druggable target for AML with FLT3/internal tandem duplication (ITD) mutations ( Wu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

et al. 2020

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Background: The tumor microenvironment (TME) has been reported to have significant value in the diagnosis and prognosis of cancers. This study aimed to identify key biomarkers in the TME of luminal breast cancer (BC).Methods: We obtained immune scores (ISs) and stromal scores (SSs) for The Cancer Genome Atlas (TCGA) luminal BC cohort from the online ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) portal. The relationships between ISs and SSs and the overall survival of luminal BC patients were assessed by the Kaplan-Meier method. The differentially expressed messenger RNAs (DEmRNAs) related to the ISs and SSs were subjected to functional enrichment analysis. Additionally, a competing endogenous RNA (ceRNA) network was constructed with differentially expressed microRNAs (DEmiRNAs) and long noncoding RNAs (DElncRNAs). Furthermore, a protein–protein interaction (PPI) network was established to analyze the DEmRNAs in the ceRNA network. Then, survival analysis of biomarkers involved in the ceRNA network was carried out to explore their prognostic value. Finally, these biomarkers were validated using the luminal BC dataset from the Gene Expression Omnibus (GEO) database.Results: The results showed that ISs were significantly associated with longer survival times of luminal BC patients. Functional enrichment analysis showed that the DEmRNAs were mainly associated with immune response, antigen binding, and the extracellular region. In the PPI network, the top 10 DEmRNAs were identified as hub genes that affected the TME of luminal BC. Finally, two DEmiRNAs, two DElncRNAs, and 17 DEmRNAs of the ceRNA network associated with the TME were shown to have prognostic value. Subsequently, the expression of 15 prognostic biomarkers was validated in one additional dataset (GSE81002). In particular, one lncRNA (GVINP1) and five mRNAs (CCDC69, DOCK2, IKZF1, JCHAIN, and NCKAP1L) were novel biomarkers.Conclusions: Our studies demonstrated that ISs were associated with the survival of luminal BC patients, and a set of novel biomarkers that might play a prognostic role in the TME of luminal BC was identified.

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Section: Discussionmentioning

confidence: 99%

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

et al. 2020

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“…Additionally, DOCK2 plays a critical role in the modulation of the immune system [56]. Hu et al [57] have reported that low expression of DOCK2 is associated with poorer prognosis of acute myeloid leukemia. Recent study reported that DOCK2 hypermethylation was associated with biochemical recurrence after radical prostatectomy in prostate cancer [58].…”

Section: Discussionmentioning

confidence: 99%

Genomic landscape of the immune microenvironments of brain metastases in breast cancer

Xie

Yuan

et al. 2020

J Transl Med

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Background: This study was intended to investigate the genomic landscape of the immune microenvironments of brain metastases in breast cancer. Methods: Three gene expression profile datasets (GSE76714, GSE125989 and GSE43837) of breast cancer with brain metastases were downloaded from Gene Expression Omnibus (GEO) database. After differential expression analysis, the tumor immune microenvironment and immune cell infiltration were analyzed. Then immune-related genes were identified, followed by function analysis, transcription factor (TF)-miRNA-mRNA co-regulatory network analysis, and survival analysis of metastatic recurrence. Results: The present results showed that the tumor immune microenvironment in brain metastases was immunosuppressed compared with primary caner. Compared with primary cancer samples, the infiltration ratio of plasma cells in brain metastases samples was significantly higher, while the infiltration ratio of macrophages M2 cells in brain metastases samples was significantly lower. Total 42 immune-related genes were identified, such as THY1 and NEU2. CD1B, THY1 and DOCK2 were found to be implicated in the metastatic recurrence of breast cancer. Conclusions: Targeting macrophages or plasma cells may be new strategies for immunotherapy of breast cancer with brain metastases. THY1 and NEU2 may be potential therapeutic targets for breast cancer with brain metastases, and THY1, CD1B and DOCK2 may serve as potential prognostic markers for improvement of brain metastases survival.

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“…Meanwhile, DOCK2 belonging to the Rho GEFs family activates GTPase which has the opposite function compared with Rho GAPs. Also, it was an independent favorable prognostic factor for both EFS and OS in AML [40]. Thus, in addition to being associated with GTPase, some regulators of Rho GTPase may have other functions in cancer.…”

Section: Discussionmentioning

confidence: 94%

The Role of ARHGAP9: Clinical Implication and Potential Function in Acute Myeloid Leukemia

Han

Wang

et al. 2020

Preprint

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Background: Rho GTPase activating protein 9 (ARHGAP9) is expressed in many cancers and can inactivate Rho GTPases that are key regulators of cytoskeletal dynamics. However, the exact role of ARHGAP9 in acute myeloid leukemia (AML) is still unclear. Methods: We compared the transcriptional expression, prognosis, differentially expressed genes, function enrichment, and hub genes in AML patients based on published data in UALCAN, GEPIA, Gene Expression Omnibus (GEO), the Human Protein Atlas (HPA), Cancer Cell Line Encyclopedia (CCLE), LinkedOmics, Metascape, and String databases. Data from the Cancer Genome Atlas (TCGA) database was used to evaluate the correlations between ARHGAP9 expression and various clinicopathological parameters as well as the significantly different genes associated with ARHGAP9 expression.Results: We found that ARHGAP9 expression was higher in AML patient tissues and cell lines than the corresponding control tissues and other cancer types. Furthermore, ARHGAP9 over-expression was associated with shorter overall survival (OS) in AML patients. Compared with the ARHGAP9low group, ARHGAP9high patients received only chemotherapy showed the significantly worse OS and event-free survival (EFS), but no significant difference after treatment with autologous or allogeneic hematopoietic stem cell transplantation (auto/allo-HSCT). In addition, ARHGAP9high patients undergoing auto/allo-HSCT had significantly better prognosis in OS and EFS than those receiving only chemotherapy. Because most of the overlapping gene between the significantly different genes and co-expression genes were enriched in the immune functions, suggesting an immune regulation potential of ARHGAP9 in AML. Thirty-two hub genes were identified from the differently expressed genes, within which the KIF20A had significant prognostic value for AML.Conclusions: Our results demonstrated that ARHGAP9 overexpression was associated with poor OS in AML patients and can be used as a prognosis biomarker. AML patients with ARHGAP9 over-expression could benefit from auto/allo-HSCT rather than chemotherapy.

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High expression of DOCK2 indicates good prognosis in acute myeloid leukemia

Cited by 13 publications

References 27 publications

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

Identification of Tumor Microenvironment-Related Prognostic Biomarkers in Luminal Breast Cancer

Genomic landscape of the immune microenvironments of brain metastases in breast cancer

The Role of ARHGAP9: Clinical Implication and Potential Function in Acute Myeloid Leukemia

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