High Expression of
            <i>DNAJA1</i>
            (
            <i>Hdj2</i>
            ) Predicts Unfavorable Survival Outcomes in Breast Cancer

Ileri, Furkan Celebi; Acun, Tolga

doi:10.2217/bmm-2020-0728

Cited by 7 publications

(6 citation statements)

References 31 publications

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“…30 DNAJA1 accumulates unfolded mutp53 in HNSCC cells and promotes tumor metastasis. 31 By using a variety of assays, Ileri et al 32 demonstrated that DNAJA1 expression in clinical tumor tissues was significantly higher than in normal tissues and that high DNAJA1 mRNA expression was associated with low survival in breast cancer. NDRG3 has been implicated in many types of cancer and is a member of the NDRG family.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive profiling of endocrine metabolism identifies a novel signature with robust predictive value in ovarian cancer

Yu,

Luo,

Guo

et al. 2024

The Journal of Gene Medicine

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BackgroundThe cell endocrine pathway is a critical physiological process composed of the endoplasmic reticulum, Golgi apparatus and associated vesicles. Loss of enzymes or proteins can cause dysfunction of endoplasmic reticulum and Golgi apparatus and affect secretion pathways leading to a variety of human diseases, including cancer.MethodsThe single‐cell RNA sequencing and single nucleotide variant principal component analysis data of ovarian cancer were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) datasets. Eighty‐four genes from SECRETORY_PATHWAYs were obtained from the gene set enrichment analysis (GSEA) website. Univariate cox regression analyses and ConsensusClusterPlus were used to identify prognostic genes and molecular subtypes, which were validated using the tumor immune dysfunction and exclusion (i.e. TIDE) analysis and gene mutation analysis. A prognosis model was established by randomForestSRC. Abundant infiltrated immune cells and pathway enrichment analyses were carried out, respectively, through ssGSEA, ESTIMATE, MCP‐counter and GSEA. The drug sensitive analysis was performed using pRRophetic package. Immunotherapy datasets and pan‐carcinoma analysis were used to examine the performance of prognostic model.ResultsEighteen prognostic genes from SECRETORY_PATHWAYs were found in both TCGA and GEO datasets. Next, two clusters (C1 and C2) were determined, for which C1 with a poor prognosis had higher immune infiltration. Tumor‐related pathways, such as PATHWAYS_IN_CANCER and B_CELL_RECEPTOR_SIGNALING_PATHWAY, were enriched in C1. Moreover, C2 was suitable for immunotherapy. A four‐gene (DNAJA1, NDRG3, LUZP1 and ZCCHC24) signature was developed and successfully validated. RiskScore of higher levels were significantly associated with worse prognoses. An enhanced immune infiltration, increased pathways score and inappropriate immunotherapy were observed in the high RiskScore group. The high‐ and low‐RiskScore groups had different drug sensitivities. Immunotherapy datasets and pan‐carcinoma analysis indicated that the low RiskScore group may benefit from immunotherapy.ConclusionsBased on the perspective of the secretory signaling pathway, a robust prognostic signature with great performances was determined, which may provide clues for clinical precision treatment of ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Comprehensive profiling of endocrine metabolism identifies a novel signature with robust predictive value in ovarian cancer

Yu,

Luo,

Guo

et al. 2024

The Journal of Gene Medicine

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“…DNAJA1 , a member of J-domain containing proteins or heat shock protein 40, is evidenced to prevent unfolded mutp53 from proteasomal degradation, which is associated with several cancers. 24,25 It was found that DNAJA1 promoted tumor metastasis by accumulating unfolded mutp53. 26 TAGLN is a regulator of the actin cytoskeleton, and affects the survival, migration, and apoptosis of various cancer cells to varying degrees.…”

Section: Discussionmentioning

confidence: 99%

“…In this present study, we identi ed 3 prognostic biomarkers of malignant tumor cells in the WT tissue, including DNAJA1, TAGLN, and NES. DNAJA1, a member of J-domain containing proteins or heat shock protein 40, is evidenced to prevent unfolded mutp53 from proteasomal degradation, which is associated with several cancers [17,18]. It was found that DNAJA1 promoted tumor metastasis by accumulating unfolded mutp53 [19].…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a prognostic model based on a single-cell RNA-seq in Wilms tumor in children

Zhao

Ning

et al. 2023

Journal of Investigative Medicine

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To analyze the heterogeneity between different cell types in pediatric Wilms tumor (WT) tissue, and identify the differentially expressed genes (DEGs) of malignant tumor cells, thereby establishing a prognostic model. The single-cell sequencing data of pediatric WT tissues were downloaded from the public database. Data filtration and normalization, principal component analysis, and T-distributed stochastic neighbor embedding cluster analysis were performed using the Seurat package of R language. Cells were divided into different clusters, malignant tumor cells were extracted, and DEGs were obtained. Then, the pseudo-time trajectory analysis was performed. Prognostic biomarkers were determined by univariate and multivariate COX regression analyses and LASSO regression analysis. Kaplan–Meier survival analysis and receiver operator characteristic curve analysis were performed. Combined with the prognostic biomarkers and clinical characteristics, a nomogram was generated to predict WT prognosis. The prognostic power was validated in the external datasets. Cells in the WT tissue were divided into 10 clusters. Three prognostic biomarkers that affected the survival time of patients were screened from 215 DEGs in malignant tumor cells, and a nomogram was constructed using the three genes and clinical characteristics. The area under the curve (AUC) values of 3- and 5-year disease-free survival were 0.756 and 0.734, respectively. In the external validation dataset, the AUC value of this nomogram model was 0.826. Based on the single-cell RNA-seq, we recognized cell clusters in the WT tissue of children, identified prognostic biomarkers in malignant tumor cells, and established a comprehensive prognostic model. Our findings might provide new ideas and methods for the diagnosis and treatment of WT.

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“…It is responsible for many cell activities, such as unfolding misfolded protein, polypeptide chain folding, transmembrane transport of polypeptide, assembling and disassembling protein complex, and regulation of protein formation [ 13 , 14 ]. In recent years, emerging in tumor-related fields, DNAJA1 has been identified as biomarker for pancreatic cancer and breast cancer [ 12 , 15 ]. DNAJA1 promotes cancer metastasis through interaction with mutant p53 in head and neck squamous cell carcinoma [ 16 ] and enhances the radiotherapy resistance of glioma cells [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

DNAJA1 Stabilizes EF1A1 to Promote Cell Proliferation and Metastasis of Liver Cancer Mediated by miR-205-5p

Ren

Bai

2022

Journal of Oncology

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Liver cancer is one of the most common and aggressive malignancies worldwide with poor prognosis. Studies on pathogenesis of liver cancer are urgently demanded to develop better treatment strategy. Here, we found that overexpression of DnaJ heat shock protein family (Hsp40) member A1 (DNAJA1) increased cell proliferation, invasion, and angiogenesis in Huh 7 and HepG2 cells, while depletion of DNAJA1 in MHCC-97H and HCC-M3 showed opposite effects. In vivo functional assays indicated that DNAJA1 promoted tumor growth and pulmonary metastasis in mice. Mechanistically, as a direct target of miR-205-5p, DNAJA1 promoted proliferation and metastasis of liver cancer cells by stabilizing eukaryotic elongation factor 1A1 (EF1A1). Moreover, DNAJA was markedly upregulated in liver cancer tissues ( P < 0.05 ) and was significantly associated with poor prognosis. And its expression was correlated with differentiation ( P < 0.001 ), dissemination ( P < 0.001 ), and serum AFP ( P = 0.029 ). The mRNA levels of miR-205-5p and DNAJA1 were negatively correlated in liver cancer. In conclusion, our study reveals that DNAJA1 acts as an oncogene in liver cancer via miR-205-5p/EF1A1 axis and might be a potential biomarker to predict the prognosis for liver cancer patients.

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High Expression of DNAJA1 ( Hdj2 ) Predicts Unfavorable Survival Outcomes in Breast Cancer

Cited by 7 publications

References 31 publications

Comprehensive profiling of endocrine metabolism identifies a novel signature with robust predictive value in ovarian cancer

Comprehensive profiling of endocrine metabolism identifies a novel signature with robust predictive value in ovarian cancer

Development and validation of a prognostic model based on a single-cell RNA-seq in Wilms tumor in children

DNAJA1 Stabilizes EF1A1 to Promote Cell Proliferation and Metastasis of Liver Cancer Mediated by miR-205-5p

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