Overexpression of DDX49 in prostate cancer is associated with poor prognosis.

BACKGROUND: There is increasing evidence that DEAD-box helicases (DDX) can act either as promoters or suppressors in various cancer types. Nevertheless, the function of DDX49 in prostate cancer (PCa) is unknown. This study reveals the prognostic and predictive value of DDX49 in PCa. METHODS: First, we evaluated the expression of DDX49 between PCa and normal tissues based on TCGA and GEO databases. Univariate and multivariate regression analyses were conducted to reveal the risk factors for PCa recurrence. A K-M curve was employed to assess the relationship between DDX49 and recurrence-free survival. In vitro, DDX49 expression was evaluated in PCa and normal prostate cell lines. Furthermore, we constructed a shDDX49 lentivirus to knock down the expression of DDX49. Celigo® Image Cytometer and MTT assay were performed to analyse cell proliferation in PC-3 cells. Cell cycle distribution was detected with flow cytometry analysis. Apoptosis affected by the lack of DDX49 was metred with the PathScan® Stress and Apoptosis Signalling Antibody Array Kit. RESULTS: This study shows a high increase in DDX49 in PCa tissues in comparison with normal tissues and that increased DDX49 indicates a poor prognosis among PCa patients. Meanwhile, DDX49 knockdown suppressed the proliferation and migration of PC-3 cells, causing cell cycle arrest in the G1 phase. Stress and apoptosis pathway analysis revealed that the phosphorylation of HSP27, p53, and SAPK/JNK was reduced in the DDX49 knockdown group compared with the control group. CONCLUSIONS: In summary, these results suggest that high expression of DDX49 predicts a poor prognosis among PCa patients. Downregulation of DDX49 can suppress cell proliferation, block the cell cycle, and facilitate cell apoptosis. Therefore, knockdown of DDX49 is a promising novel therapy for treating patients with PCa.

Positive response of a recurrent clear cell sarcoma to anlotinib combined with chemotherapy: A case report.

RATIONALE: Renal clear cell sarcoma is a rare and highly invasive malignant renal tumor that easily relapses after treatment. Recurrent recurrent clear cell carcinoma (CCSK) responds poorly to chemotherapy and has no established standardized treatment, and need to be explored potentially useful treatments. PATIENT CONCERNS: A 18-years-old patient with renal clear cell sarcoma recurrence after open radical nephrectomy. DIAGNOSIS: Recurrent clear cell sarcoma. INTERVENTIONS: After chemotherapy alone failed, the patient received 6 courses of anlotinib combined with chemotherapy. The tumor had significantly reduced in size and the recurrent tumor and part of the liver were resected. OUTCOMES: No tumor recurrence or metastasis was detected during the follow-up 8 months after the operation. LESSONS: This is the first report describing the use of anlotinib in treating CCSK. We believe that anlotinib combined with chemotherapy may be a useful treatment option for patients with recurrent CCSK.

Identification and validation of an E2F-related gene signature for predicting recurrence-free survival in human prostate cancer.

BACKGROUND: It is well-established that biochemical recurrence is detrimental to prostate cancer (PCa). In the present study, we explored the mechanisms underlying PCa progression. METHODS: Five cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases were used to perform gene set variation analysis (GSVA) between nonrecurrent and recurrent PCa patients. We obtained the intersection of pathway enrichment results and extracted the corresponding gene list. LASSO Cox regression analysis was used to identify recurrence-free survival (RFS)-related significant genes and establish an RFS prediction gene signature and nomogram. MTT and colony formation assays were conducted to validate our findings. RESULTS: The E2F signaling pathway was activated in recurrent PCa patients compared to nonrecurrent patients. We established an E2F-related gene signature for RFS prediction based on the four identified E2F-related genes (CDKN2C, CDKN3, RACGAP1, and RRM2) using LASSO Cox regression in the Memorial Sloan Kettering Cancer Center (MSKCC) cohort. The risk score of each patient in MSKCC was calculated based on the expression levels of CDKN2C, CDKN3, RACGAP1, and RRM2. PCa patients with low-risk scores exhibited higher RFS than those with high-risk scores. Receiver operating characteristic (ROC) curve analysis validated the good performance and prognostic accuracy of the E2F-related gene signature, which was validated in the TCGA-prostate adenocarcinoma (TCGA-PRAD) cohort. Compared to patients with low Gleason scores and early T stages, PCa patients with high Gleason scores and advanced T stages had high-risk scores. Moreover, the E2F-related gene signature-based nomogram yielded good performance in RFS prediction. Functional experiments further confirmed these results. CONCLUSIONS: The E2F signaling pathway is associated with biochemical recurrence in PCa. Our established E2F-related gene signature and nomogram yielded good accuracy in predicting the biochemical recurrence in PCa.

Expression of basement membrane genes and their prognostic significance in clear cell renal cell carcinoma patients.

Background: Clear cell renal cell carcinoma (ccRCC) is a malignant tumor with limited treatment options. A recent study confirmed the involvement of basement membrane (BM) genes in the progression of many cancers. Therefore, we studied the role and prognostic significance of BM genes in ccRCC. Methods: Co-expression analysis of ccRCC-related information deposited in The Cancer Genome Atlas database and a BM geneset from a recent study was conducted. The differentially expressed BM genes were validated using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Least absolute shrinkage and selection operator regression and univariate Cox regression analyses were performed to identify a BM gene signature with prognostic significance for ccRCC. Multivariate Cox regression, time-dependent receiver operating characteristic, Kaplan-Meier, and nomogram analyses were implemented to appraise the prognostic ability of the signature and the findings were further verified using a Gene Expression Omnibus dataset. Additionally, immune cell infiltration and and pathway enrichment analyses were performed using ImmuCellAI and Gene Set Enrichment Analysis (GSEA), respectively. Finally, the DSIGDB dataset was used to screen small-molecule therapeutic drugs that may be useful in treating ccRCC patients. Results: We identified 108 BM genes exhibiting different expression levels compared to that in normal kidney tissues, among which 32 genes had prognostic values. The qRT-PCR analyses confirmed that the expression patterns of four of the ten selected genes were the same as the predicted ones. Additionally, we successfully established and validated a ccRCC patient prediction model based on 16 BM genes and observed that the model function is an independent predictor. GSEA revealed that differentially expressed BM genes mainly displayed significant enrichment of tumor and metabolic signaling cascades. The BM gene signature was also associated with immune cell infiltration and checkpoints. Eight small-molecule drugs may have therapeutic effects on ccRCC patients. Conclusion: This study explored the function of BM genes in ccRCC for the first time. Reliable prognostic biomarkers that affect the survival of ccRCC patients were determined, and a BM gene-based prognostic model was established.

EPM2A acts as a protective factor in prostate cancer, evidence from a real-world patient cohort.

EPM2A encodes a dual specificity phosphatase and has been proven to be a potential biomarker in several cancers but has not been mentioned in prostate cancer (PCA). We investigated the prognostic and therapeutic value of EPM2A in PCA. The TCGA-PRAD cohort was collected to evaluate the differential expression, prognostic value, immunocyte infiltration and drug sensitivity of EPM2A in PCA. We constructed a nomogram model to predict the recurrence probability for PCA patients. Immunohistochemistry was used to validate the different transcript levels of EPM2A between tumor and normal tissues. A real-world AHMU-PC cohort was employed for validation. The results showed decreased expression of EPM2A in 95.65% of tumor tissues and was related to their prognosis, especially PCA (p = 0.008, HR = 0.57, 95% CI: 0.371-0.863). Further multiple analysis by adjusting clinical features revealed that EPM2A acted as an independent prognostic factor (p = 0.014, HR = 0.589, 95% CI: 0.386-0.898). Pathway enrichment analysis showed variable signaling activation between high EPM2A expression patients (HEXP) and low EPM2A expression patients (LEXP). The HEXP group contained higher infiltration of immunocytes than the LEXP group, as well as high levels of PD-1, PD-L1 and PD-L2, while LEXP patients were more sensitive to cisplatin, paclitaxel and bicalutamide therapy. The nomogram containing the EPM2A group, T stage and Gleason score showed a preferable prognostic value (AUC = 0.755; Hosmer‒Lemeshow, p = 0.486). In validation, we confirmed the lower transcript level of EPM2A in PCA than in normal tissues (120.5 ± 2.159 vs. 138.3 ± 1.83, p = 0.035) and correlated it with the expression level of PD-1 (R = 0.283). Among the 66 patients from the AHMU-PC cohort, we further validated the function of EPM2A in PCA patients. HEXP patients had longer recurrence-free survival times (1207 ± 110 vs. 794.2 ± 97.02, p = 0.0063) and favorable prognoses (HR: 0.417, 95% CI: 0.195-0.894, p = 0.0245). Collectively, we identified the prognostic value of EPM2A in PCa via a bioinformatics method. Patients with higher EPM2A may be more sensitive to immunotherapy, and patients with lower EPM2A were more suitable for bicalutamide, cisplatin and paclitaxel therapy.

Outcomes of Robot-Assisted Laparoscopic Isthmus Division Using Endoscopic Transection Equipment in the Treatment of Symptomatic Horseshoe Kidney.

Background: The surgical treatment of horseshoe kidney (HSK) remains a huge challenge because of the complex anatomy and abnormal blood vessel distribution. Therefore, this study aimed to evaluate the surgical technique and outcomes of robot-assisted laparoscopic isthmus division using endoscopic transection equipment (endoscopic linear stapler; Ethicon, ECHELON 60 FLEX™) in the treatment of symptomatic HSK and to conduct a literature review. Materials and Methods: Patients with HSK who underwent robot-assisted laparoscopic isthmus division using endoscopic transection equipment from August 2015 to August 2019 at the First Affiliated Hospital of Anhui Medical University in China were recruited. Isthmus division was conducted using an endoscopic linear stapler. Results: All 10 surgeries were performed successfully. Major organs and large blood vessels were effectively protected. Only 1 patient presented with postoperative perinephric effusion. The mean operative time was 179 minutes, and the mean length of the postoperative hospital stay was 6 days. During the 1- to 5-year follow-up, all patients were cured with mitigated symptoms and improved renal function, except for 1 patient with transitional cell carcinoma who died of multiple metastases 18 months postoperatively. Conclusion: Robot-assisted laparoscopic isthmus division using endoscopic transection equipment is a safe and effective method to manage patients with symptomatic HSK and to help them have few complications and quick recovery. Clinical Trial Registration No: Quick-PJ 2021-03-18.