DJ-1 In Patients Research Articles

Irradiation induces DJ-1 secretion from esophageal squamous cell carcinoma cells to accelerate metastasis of bystander cells via a TGF-β1 positive feedback loop

BackgroundRadiation-induced bystander effect (RIBE) can promote tumor metastasis contributing to the failure of radiotherapy for esophageal squamous cell carcinoma (ESCC). Aberrant expression of DJ-1 has been identified in ESCC; however, the relationship between DJ-1 and RIBE in ESCC remains unknown.MethodsWe detected DJ-1 in the serum and cell supernatants by enzyme-linked immunosorbent assay (ELISA) and evaluated tumor metastasis by phenotypic experiments in vivo and in vitro. RNA-seq, mass spectrometry, western blot (WB), immunoprecipitation (IP), and dual-luciferase reporter assays were performed to explore the underlying mechanisms.ResultsDJ-1 was highly expressed in the serum of patients with ESCC receiving radiotherapy and was significantly overexpressed in the medium of ESCC cells receiving irradiation. DJ-1 promoted tumor metastasis via the TGF-β1 pathway. Mechanistic studies revealed that DJ-1 bound to HSC70 to promote Smad3 phosphorylation and nuclear aggregation in a protein-interaction manner, which activated the transcription of Thrombospondin-1 (TSP1). Subsequently, the activation of TGF-β1 by TSP1 re-promoted Smad3 phosphorylation and nuclear aggregation, constituting a positive feedback loop to strengthen the metastasis of ESCC cells, which was effectively blocked by LY2109761 and LSKL. Moreover, higher levels of serum DJ-1 in patients with ESCC were related to a poorer prognosis of radiotherapy.ConclusionsIrradiation can induce ESCC cells secreting DJ-1. Secreted DJ-1 enters bystander cells to initiate activation of the TGF-β1 pathway via the DJ-1/HSC70/Smad3 signaling axis. The TSP1/TGF-β1/Smad3 positive feedback pathway constitutes the core pathway that promotes ESCC metastasis. DJ-1 is a useful biomarker for predicting the efficacy of radiotherapy and a potential therapeutic target for reversing RIBE in ESCC.Graphical Schematic diagram showing the underlying mechanismthat irradiation-induced secretion of DJ-1 accelerates the metastasis ofbystander ESCC cells.

Effects of carboplatin combined with paclitaxel-based intraperitoneal hyperthermic perfusion chemotherapy on serum levels of HE4 and DJ-1 in patients with advanced recurrent ovarian cancer.

Objective:To analyze the effects of carboplatin combined with paclitaxel-based intraperitoneal hyperthermic perfusion chemotherapy (IPCH) on serum levels of human epididymis protein 4 (HE4) and mitogen-dependent oncogene-1 (DJ-1) in patients with advanced recurrent ovarian cancer (OC).Methods:From July 2019 to July 2020, patients with advanced recurrent OC (n=92) treated in Affiliated Hospital of Hebei Engineering University were selected as study subjects. According to the random number table method, patients were divided into control group and observation group. Patients in the control group were treated with carboplatin combined with paclitaxel-based intravenous chemotherapy, and patients in the observation group were treated with carboplatin combined with paclitaxel-based IPCH. The therapeutic effects, serum levels of HE4, DJ-1 and human kallikrein 10 (HK-10), peripheral blood immune indexes and adverse reactions of patients were compared between the two groups.Results:The response rate of the observation group was significantly higher than that of the control group (p<0.05); after treatment, the indexes of HE4, DJ-1 and HK-10 in the two groups were significantly decreased, while the indexes of CD3+CD4+, CD3+CD56+ and CD3+CD4+/CD3+CD8+ were significantly increased; moreover, significantly lower indexes of HE4, DJ-1 and HK-10 and significantly higher indexes of CD3+CD4+, CD3+CD56+ and CD3+CD4+/CD3+CD8+ were found in the observation group when compared with the control group (p<0.05). The severity of myelosuppression, nausea and vomiting in the observation group was significantly lower than that in the control group, and the total tumor metastasis rate in the observation group was significantly lower than that in the control group (p<0.05).Conclusions:Carboplatin combined with paclitaxel IPCH had obvious inhibitory effects on HE4, DJ-1 and other serum tumor markers in patients with advanced recurrent OC, with a more prominent clinical effect, and could further significantly reduce the risk of adverse reactions and metastasis.

Frequency of mutations in PRKN, PINK1, and DJ1 in Patients With Early-Onset Parkinson Disease from neighboring countries in Central Europe

IntroductionApproximately 10% of patients with Parkinson disease (PD) present with early-onset disease (EOPD), defined as diagnosis before 50 years of age. Genetic factors are known to contribute to EOPD, with most commonly observed mutations in PRKN, PINK1, and DJ1 genes. The aim of our study was to analyze the frequency of PRKN, PINK1, and DJ1 mutations in an EOPD series from 4 neighboring European countries: Czech Republic, Germany, Poland, and Ukraine. MethodsDiagnosis of PD was made based on UK Brain Bank diagnostic criteria in departments experienced in movement disorders (1 from Czech Republic, 1 from Germany, 9 from Poland, and 3 from Ukraine). EOPD was defined as onset at or before 50 years of age. Of the 541 patients recruited to the study, 11 were Czech, 38 German, 476 Polish, and 16 Ukrainian. All cohorts were fully screened with Sanger sequencing for PRKN, PINK1, and DJ1 and multiplex ligation-dependent probe amplification for exon dosage. ResultsPRKN homozygous or double heterozygous mutations were identified in 17 patients: 1 Czech (9.1%), 1 German (2.6%), 14 Polish (2.9%), and 1 Ukrainian (6.3%). PINK1 homozygous mutations were only identified in 3 Polish patients (0.6%). There were no homozygous or compound heterozygous DJ1 mutations in analyzed subpopulations. One novel variant in PRKN was identified in the Ukrainian series. ConclusionIn the analyzed cohorts, mutations in the genes PRKN, PINK1, and DJ1 are not frequently observed.

PARK2, PINK1, and DJ1 in patients with early-onset Parkinson’s disease in four European countries. (2506)

PARK2, PINK1, and DJ1 in patients with early-onset Parkinson’s disease in four European countries. (2506)

DJ-1 is a useful biomarker for invasive extrahepatic cholangiocarcinoma

We have previously reported that DJ-1 protein is up-regulated in cholangiocarcinoma compared with non-neoplastic epithelium of the bile duct in a study using liquid-chromatography mass spectrometry-based proteomics. The aim of this study was to clarify whether DJ-1 expression offers a biomarker for patients with invasive extrahepatic cholangiocarcinoma (EHCC) who undergo surgical resection with curative intent. Positive immunohistochemical (IHC) staining of DJ-1 was significantly more frequent in the cytoplasm of 96 invasive EHCCs (n = 28, 29.2%) than in that of 66 non-neoplastic epithelial lesions adjacent to invasive EHCC (n = 7, 10.6%; P = .006). No significant difference in clinicopathological features was evident between invasive EHCC patients with negative (n = 68) and positive (n = 28) IHC staining. However, negative IHC staining for DJ-1 in cytoplasm was selected as an independent risk factor for adverse prognosis on multivariate analysis (P = .004, hazard ratio 2.13, 95% confidence interval 1.28-3.57). Serum levels of DJ-1 in 16 invasive EHCC patients with metastasis were compared with 12 invasive EHCC patients without metastasis. Serum levels of DJ-1 tended to be higher in 16 patients with metastasis (median, 40.9 ng/ml) than in 12 patients without (27.6 ng/ml, P = .137). In addition, patients with high serum levels (≥ 40 ng/ml) of DJ-1 tended to have metastasis more frequently than those without (P = .054, Fisher's exact test). We concluded that IHC staining pattern and serum level of DJ-1 in patients with invasive EHCC might be predictive of prognosis and metastasis, respectively.