Metastasis is the major cause of prostate cancer (PCa)-related mortality. Epithelial-mesenchymal transition (EMT) is a vital characteristic feature that empowers cancer cells to adapt and survive at the beginning of metastasis. Therefore, it is essential to identify the regulatory mechanism of EMT in metastatic prostate cancer (mPCa) and to develop a novel therapy to block PCa metastasis. Here, we discovered a novel PCa metastasis oncogene, DEP domain containing 1B (DEPDC1B), which was positively correlated with the metastasis status, high Gleason score, advanced tumor stage, and poor prognosis. Functional assays revealed that DEPDC1B enhanced the migration, invasion, and proliferation of PCa cells in vitro and promoted tumor metastasis and growth in vivo. Mechanistic investigations clarified that DEPDC1B induced EMT and enhanced proliferation by binding to Rac1 and enhancing the Rac1-PAK1 pathway. This DEPDC1Bmediated oncogenic effect was reversed by a Rac1-GTP inhibitor or Rac1

Matrine may be used to treat prostate cancer patients to increase the levels of GADD45B to inhibit tumor invasion and improve patient survivals.

Summary Background Chronic subdural hematoma (CSDH) is a common neurological disease, and the surgical evacuation of subdural collection remains the primary treatment approach for symptomatic patients. Postoperative recurrence is a serious complication, and several factors are correlated with postoperative recurrence. Methods We searched Embase, Web of Science, PubMed, and Cochrane Library from their establishment to September 2020. Reports on randomized, prospective, retrospective, and overall observational studies on the management of surgical patients with CSDH were searched, and an independent reviewer performed research quality assessment. Factors that affect the postoperative recurrence of CSDH were extracted: social demographics, drugs (as the main or auxiliary treatment), surgical management, imaging, and other risk factors. We evaluated the recurrence rate of each risk factor. A random effect model was used to perform a meta-analysis, and each risk factor affecting the postoperative recurrence of CSDH was then evaluated and graded. Findings In total, 402 studies were included in this analysis and 32 potential risk factors were evaluated. Among these, 21 were significantly associated with the postoperative recurrence of CSDH. Three risk factors (male, bilateral hematoma, and no drainage) had convincing evidence. The classification of evidence can help clinicians identify significant risk factors for the postoperative recurrence of CSDH. Interpretation Only few associations were supported by high-quality evidence. Factors with high-quality evidence may be important for treating and preventing CSDH recurrence. Our results can be used as a basis for improving clinical treatment strategies and designing preventive methods. Funding No funding was received.

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Objective: To explore the genetic changes in the progression of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC) and the reason why these cancers resist existing therapies. Methods: We employed our CRPC cell line microarray and other CRPC or NEPC datasets to screen the target gene NEIL3. Lentiviral transfection and RNA interference were used to construct overexpression and knockdown cell lines. Cell and animal models of radiotherapy were established by using a medical electron linear accelerator. Flow cytometry was used to detect apoptosis or cell cycle progression. Western blot and qPCR were used to detect changes in the protein and RNA levels. Results: TCGA and clinical patient datasets indicated that NEIL3 was downregulated in CRPC and NEPC cell lines, and NEIL3 was correlated with a high Gleason score but a good prognosis. Further functional studies demonstrated that NEIL3 had no effect on the proliferation and migration of PCa cells. However, cell and animal radiotherapy models revealed that NEIL3 could facilitate the radiotherapy sensitivity of PCa cells, while loss of NEIL3 activated radiotherapy resistance. Mechanistically, we found that NEIL3 negatively regulated the expression of ATR, and higher NEIL3 expression repressed the ATR/CHK1 pathway, thus regulating the cell cycle. Conclusions: We demonstrated that NEIL3 may serve as a diagnostic or therapeutic target for therapy-resistant patients.

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DNA damage response (DDR) plays an important role in the progression of cancers, including prostate cancer (PCa). Topoisomerase II-binding protein 1 (TopBP1) is an essential promotor of ATR-mediated DDR. Herein, we investigated the association between TopBP1 and PCa and determined its effect on the progression of PCa. The expression and clinical features of TopBP1 were analyzed using large-scale cohort of tissue microarray analyses and The Cancer Genome Atlas database, which indicated that TopBP1 was positively correlated with high Gleason Score, advanced clinical and pathological stages, the metastasis status. Multivariate analysis revealed that the upregulation of TopBP1 was an independent predictor for a worse biochemical recurrencefree survival (BCR-free survival). Furthermore, we discovered that downregulation of TopBP1 significantly suppressed the growth and migration ability of PCa lines by loss-of-function assays in vitro. Further mechanistic investigations clarified that TopBP1 promoted proliferation and migration by activating ATR-Chk1 signaling pathway.

Glioma tumor suppressor candidate region gene 1 (GLTSCR1) is associated with the progression of oligodendroglioma. However, there has been little study of GLTSCR1 in prostate cancer. In the present study, the association between the expression of GLTSCR1, and the progression and prognosis of tumors in patients with prostate cancer was assessed. An immunohistochemical analysis was performed using a human tissue microarray for GLTSCR1 at the protein expression level and the immunostaining results were evaluated against clinical variables of patients with prostate cancer. Subsequently, The Cancer Genome Atlas (TCGA) was used to validate the analysis results at the mRNA level and to study the prognostic value of GLTSCR1 in prostate cancer. Immunohistochemistry and TCGA data analysis revealed that GLTSCR1 expression in the prostate cancer tissues was significantly higher than that in the benign prostate tissues (immunoreactivity score, P=0.015; mRNA levels: cancer, 447.7±6.45 vs. benign, 343.5±4.21; P<0.001). Additionally, the increased GLTSCR1 protein expression was associated with certain clinical variables in the prostate cancer tissues, including advanced clinical stage (P<0.001), enhanced tumor invasion (P=0.003), lymph node metastasis (P=0.003) and distant metastasis (P=0.001). TCGA data revealed similar results, demonstrating that the upregulation of GLTSCR1 mRNA expression was associated with the Gleason score (P<0.001), enhanced tumor invasion (P=0.011), lymph node metastasis (P=0.001) and distant metastasis (P=0.002). Furthermore, Kaplan-Meier analysis suggested that among all patients, high GLTSCR1 expression indicated a decreased overall survival (P=0.028) and biochemical recurrence (BCR)-free survival (P=0.004), compared with patients with low GLTSCR1 expression. Finally, multivariate analysis revealed that the expression of GLTSCR1 was an independent predictor of poor BCR-free survival (P=0.049). The present study suggested that the increased expression of GLTSCR1 was associated with the progression of prostate cancer. Furthermore, GLTSCR1 may be a novel biomarker that is able to predict the clinical outcome in prostate cancer patients.