Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer

Dong, Menglu; Li, Hanning; Zhang, Rui; Li, Xingrui

doi:10.3892/ol.2020.11533

Cited by 20 publications

(26 citation statements)

References 62 publications

(61 reference statements)

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“…Although it remains to be fully elucidated what the exact functional contributions of HURP in the mitotic spindle assembly are, the strong evidence mentioned above provides important insights into the role of HURP in the control of cell cycle. Importantly, as expected, the upregulated of HURP in many common cancers is detected, including HCC [8,14], bladder cancer [15], prostate cancer [16,17], breast cancer [18,19], lung cancer [20,21], colorectal cancer [22], as well as endometrial carcinoma [23], but not in normal tissues, indicating that misregulation of its expression plays roles in carcinogenesis.…”

Section: Introductionsupporting

confidence: 70%

“…An increased number of studies have con rmed that DLGAP5 Upregulated occurs in many cancer tissues as mentioned in the introduction. DLGAP5/HURP is initially found to be upregulated in HCC by bioinformatics analysis, and the results subsequently con rmed by experiments [7], In a similar way, its Upregulated in many cancers is found by analysis of database or microarray data and experimental veri cation, such as prostate cancer [16,17], breast cancer cells [19], lung cancer [20,21], and endometrial carcinoma [23]. In the present study, our TCGA pan-cancer analysis clearly showed signi cant upregulated of DLGAP5 in at least 26 types of cancer tissues compared with the respective adjacent tissues (P < 0.001), including ccRCC, and 7 types mentioned above.…”

Section: Discussionmentioning

confidence: 69%

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Pan-cancer Analysis Combining with Experiments Indicates the Sensitivity of Renal Carcinogenesis to DLGAP5 Expression

Feng

Guo

et al. 2020

Preprint

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Background: Discs large-associated protein 5 (DLGAP5), a kinetochore ﬁbers-binding protein, has been found to function as a oncoprotein in many cancers. However, its expression patterns in normal and cancer tissues across pan-cancer, as well as the cell lines, are far from clear. Methods: Data from genotype-tissue expression (GTEx) and The Cancer Genome Atlas (TCGA) was used to analyze the DLGAP5 expression in normal tissues and cancer cell lines, respectively. The analysis of DLGAP5 expression in cancer tissues and adjacent tissues was based on data from a combined TCGA and GTEx. The associations between the expression, prognosis and cancer immune infiltrates in pan-cancer were also investigated based on TCGA and Tumor Immune Estimation Resource (TIMER), respectively. Furthermore, the analysis results of ccRCC was verified using cell lines via RNAi, western blotting, and the cytological analysis.Results: The low expression levels of DLGAP5 were observed in 31 types of common human tissues, including kidney tissue. However, its expression displayed upregulation in all the 21 tested cancer cell lines, of which kidney cancer cell lines showed a minimal upregulation. As predicted, the significant overexpression of DLGAP5 occurred in at least 26 types of common cancer tissues compared with the adjacent normal tissues. Surprisingly, in three types of kidney cancer (KICH, KIRC/ccRCC, KIRP), DLGAP5 exhibited a statistically significant, but minor, overexpression among 26 types of tested cancers. Furthermore, the survival probability of some tested cancers, including kidney cancer, were significantly related to the upregulated expression of DLGAP5. In addition, among 33 types of tested cancers, KIRC/ccRCC, LGG and LIHC showed a significant positive correlation between DLGAP5 expression and immune infiltration levels. DLGAP5 expression level was also significantly positive correlated with clinical TNM stage of ccRCC patients. Regarding ccRCC tissues and the cell lines, upregulation expression of DLGAP5 was also detected. Its knockdown inhibited the cells viability and proliferation, and compromised the cells migration and invasion. Conclusions: DLGAP5 overexpression occurred in common human cancers, including the kidney cancers. Notably, ccRCC, seemed to be particularly sensitive to the expression. DLGAP5, therefore, may be as a robust independent prognostic biomarker in ccRCC diagnosis.

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Section: Introductionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 69%

Pan-cancer Analysis Combining with Experiments Indicates the Sensitivity of Renal Carcinogenesis to DLGAP5 Expression

Feng

Guo

et al. 2020

Preprint

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“…DLGAP5 and CDC7 are potential cell cycle regulators that play roles in carcinogenesis of cancer cells. Elevated expressions of DLGAP5 were noticed in breast cancer specimens and were associated with poor prognosis [29]. Moreover, a cellular apoptosis susceptibility protein (CSE1L), is extensively expressed in certain types of cancers.…”

Section: Discussionmentioning

confidence: 99%

Astragalus Polysaccharide Regulates EGFR and ANXA1 Expression to Inhibit Tumor Growth

Li¹,

Hu²,

Li³

et al. 2021

Preprint

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Background: Astragalus polysaccharide (APS) has been frequently used as an adjuvant agent responsible for its immunoregulatory activity to enhance efficacy and reduce toxicity of chemotherapy used in the management of breast cancer. However, the other synergism mechanism of APS remains unclear. Methods: The expression profiles of breast cancer biological data (E-GEOD-10780), (E-GEOD-65194), (E-GEOD-10810), (E-GEOD-42568), (E-GEOD-61304), (E-GEOD-7904) and (E-GEOD-15852) were retrieved from European bioinformatics institute (EBI) database to identify differentially expressed genes (DEGs). Gene Ontology and pathway enrichment analyses were carried out. The protein–protein interaction (PPI) networks of the DEGs were constructed by STRING online database. Finally, STRING was applied to construct the PPI networks of the DEGs associated with cell proliferation, cell cycle and cell apoptosis from GO enrichment analysis. Subsequently, hub and common genes that might be the potential targets and possible mechanism behind APS in vivo direct anti-tumor activity on breast cancer were identified. Meanwhile, we evaluated the mRNA and protein expression levels of these key targets using multiple biological analyses.Results: In total, 116 down-regulated and 73 up-regulated differential expressed genes (DEGs) were examined from seven gene expression datasets. Top ten hub genes were obtained in four typical protein-protein interaction (PPI) network of DEGs involved in each specific biological process (BP, cell cycle, cell proliferation, cell apoptosis and death) that was related to inhibitory activity of APS in vitro against breast cancer cell lines. Four common DEGs (EGFR, ANXA1, KIF14 and IGF1) were further identified in the above four BP-PPI networks, among which EGFR and ANXA1 were the hub genes that were potentially linked to the progression of breast cancer. The results of biological detections indicated that APS could down-regulated EGFR and up-regulated ANXA1 expression.Conclusion: In conclusion, the present study may provide potential molecular therapeutic targets and a new insight into the mechanism of APS against breast cancer.

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“…Previous studies have demonstrated that these genes are involved in the pathogenesis of LUAD. For instance, the prognostic value of DLGAP5 has been assessed in other cancers, such as colorectal cancer (37), pancreatic cancer (38) and breast cancer (39). Prior studies on LUAD have also identi ed prognostic signatures including DLGAP5 (40); however, little is known about how this gene affects the development of LUAD (41,42).…”

Section: Discussionmentioning

confidence: 99%

Identification of a lncRNA-mRNA Regulatory Module for Prognosis, Classification and Potential Treatment of Lung Adenocarcinoma

Zhao

Liu

et al. 2021

Preprint

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Background: Lung cancer remains the leading cause of cancer death worldwide, with lung adenocarcinoma (LUAD) being the most prevalent subtype of lung cancer. This study aimed to identify a lncRNA-mRNA regulatory module related to the prognosis, classification, and potential treatment of LUAD.Methods: Publicly available gene expression data of three cohorts were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Differential expression analysis between LUAD and normal samples, as well as the survival analysis, was performed. Protein-protein interaction (PPI) network and co-expression analyses were conducted to further identify key genes. A least absolute shrinkage and selection operator (LASSO) Cox regression model was developed to predict overall survival. Five machine learning models, including logistic regression, K-nearest neighbor (KNN), support vector machine (SVM), random forest, and extremely gradient boosting (XGBOOST), were trained to distinguish early-stage or epidermal growth factor receptor (EGFR)-mutation LUAD from others. Furthermore, connectivity map (CMap) and molecular docking analyses were performed to identify compounds with the ability to reverse the expression profiles of the key genes.Results: A cohort comprised of 535 LUAD and 59 normal samples in TCGA was used as the training set, while the GSE31210 and GSE30219 datasets were used as validation sets. 189 mRNAs and 11 lncRNAs were differentially expressed and associated with the overall survival. 43 hub mRNAs were further identified from the PPI network, and 3 lncRNAs were significantly correlated to the expression of hub mRNAs. Six genes with nonzero coefficients were selected by using the LASSO COX regression analysis, and the corresponding risk score was derived. The time-dependent ROC and Kaplan Meier analysis demonstrated that the risk score accurately discriminates the patients with a high or low risk. KNN and XGBOOST were the best models to recognize early-stage and EGFR-mutation LUAD, respectively. Purvalanol-a and Etoposide obtained a score of -99.98 in CMap and were successfully docked with three key genes.Conclusions: A lncRNA-mRNA regulatory module, including 4 mRNAs and 2 lncRNAs, was identified, and this module can facilitate the exploration of pathogenesis of LUAD and speed up the development of new treatments for LUAD patients.

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Elevated mRNA expression levels of DLGAP5 are associated with poor prognosis in breast cancer

Cited by 20 publications

References 62 publications

Pan-cancer Analysis Combining with Experiments Indicates the Sensitivity of Renal Carcinogenesis to DLGAP5 Expression

Pan-cancer Analysis Combining with Experiments Indicates the Sensitivity of Renal Carcinogenesis to DLGAP5 Expression

Astragalus Polysaccharide Regulates EGFR and ANXA1 Expression to Inhibit Tumor Growth

Identification of a lncRNA-mRNA Regulatory Module for Prognosis, Classification and Potential Treatment of Lung Adenocarcinoma

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