Hypermethylated ITGA8 Facilitate Bladder Cancer Cell Proliferation and Metastasis.

DNA methylation plays a vital role during the development of tumorigenesis. The purpose of this study is to identify candidate DNA methylation drivers during progression of bladder cancer (BLCA). The methylation spectrum in bladder cancer tissues was detected by CHARM analysis, and methylated ITGA8 was selected for further study due to its low expression. Methylation levels in BLCA tissues and cells were detected with methylated-specific PCR (MSP), while mRNA expression and methylation of ITGA8 were detected by qRT-PCR and MSP. After treatment with 5-Aza-dC (DNA methylation inhibitor), the proliferation, migration, and invasion abilities of BLCA cells were determined by MTT, wound healing, and transwell assays, respectively. Flow cytometric analysis was performed to evaluate any variance in the cell cycle. In addition, the effect of demethylated ITGA8 on BLCA tumor growth was verified with an in vivo xenograft tumor model. Based on the methylation profiling of BLCA, ITGA8 was identified to be hypermethylated. ITGA8 methylation levels in BLCA tissues and cells were upregulated, and 5-Aza-dC significantly suppressed ITGA8 methylation levels and increased ITGA8 mRNA expression. Furthermore, after treatment with 5-Aza-dC, the propagation, migration, and invasiveness of the cancer cells were inhibited, and more cancer cells were arrested at the G0/G1 phase. In vivo assays further demonstrated that 5-Aza-dC could impede BLCA tumor growth by repressing methylation levels of ITGA8 and increasing ITGA8 mRNA expression. Hypermethylated ITGA8 facilitated BLCA progression, and 5-Aza-dC treatment inhibited BLCA cell propagation and metastasis by decreasing methylation levels of ITGA8 and inducing cell cycle arrest.

Observational Study: Clinical characteristics and Survival Rates in Patients with Prostate Cancer with Normal Prostate-Specific Antigen Concentrations.

Objectives: This study aimed to explore the clinical characteristics of patients with prostate cancer with prostate-specific antigen (PSA) concentrations of less than 4 ng/mL (normal PSA) to provide clinical insights regarding diagnosis and treatment. Methods: We recruited 35 patients with prostate cancer with normal PSA who were admitted to Xi'an People's Hospital from January 2013 to January 2018, and further determined their clinical characteristics, serum PSA concentration, prostate volume, tumor pathology, surgical margins, seminal vesicle invasion, lymph node metastasis, Gleason score, TNM staging, risk classification, and survival, and described the patients' interventions and treatments. All patients and their families signed informed consent forms before enrollment. Results: In our study, we observed a 3-year survival rate of 77.14% for patients with prostate cancer and normal PSA concentrations. This outcome can be attributed to several clinical characteristics, including the absence of obvious clinical presentation, a high detection rate of seminal vesicle invasion, as well as high Gleason scores and risk levels. The primary outcome, 3-year survival rate, reflects the long-term prognosis of this specific patient subgroup. We also conducted correlation analyses to better understand the relationships between these clinical characteristics and patient survival.

Systematic Investigation of Immune-Related lncRNA Landscape Reveals a Potential Long Non-Coding RNA Signature for Predicting Prognosis in Renal Cell Carcinoma.

Background: Renal cell carcinoma (RCC) is the predominant type of malignant tumor in kidney cancer. Finding effective biomarkers, particularly those based on the tumor immune microenvironments (TIME), is critical for the prognosis and diagnosis of RCC. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) play a crucial role in cancer immunity. However, the comprehensive landscape of immune infiltration-associated lncRNAs and their potential roles in the prognosis and diagnosis of RCC remain largely unexplored. Methods: Based on transcriptomic data of 261 RCC samples, novel lncRNAs were identified using a custom pipeline. RCC patients were classified into different immune groups using unsupervised clustering algorithms. Immune-related lncRNAs were obtained according to the immune status of RCC. Competing endogenous RNAs (ceRNA) regulation network was constructed to reveal their functions. Expression patterns and several tools such as miRanda, RNAhybrid, miRWalk were used to define lncRNAs-miRNAs-mRNAs interactions. Univariate Cox, LASSO, and multivariate Cox regression analyses were performed on the training set to construct a tumorigenesis-immune-infiltration-related (TIR)-lncRNA signature for predicting the prognosis of RCC. Independent datasets involving 531 RCC samples were used to validate the TIR-lncRNA signature. Results: Tens of thousands of novel lncRNAs were identified in RCC samples. Comparing tumors with controls, 1,400 tumorigenesis-related (TR)-lncRNAs, 1269 TR-mRNAs, and 192 TR-miRNAs were obtained. Based on the infiltration of immune cells, RCC patients were classified into three immune clusters. By comparing immune-high with immune-low groups, 241 TIR-lncRNAs were identified, many of which were detected in urinary samples. Based on lncRNA-miRNA-mRNA interactions, we constructed a ceRNA network, which included 25 TR-miRNAs, 28 TIR-lncRNAs, and 66 TIR-mRNAs. Three TIR lncRNAs were identified as a prognostic signature for RCC. RCC patients in the high-risk group exhibited worse OS than those in the low-risk group in the training and testing sets (p < 0.01). The AUC was 0.9 in the training set. Univariate and multivariate Cox analyses confirmed that the TIR-lncRNA signature was an independent prognostic factor in the training and testing sets. Conclusion: Based on the constructed immune-related lncRNA landscape, 241 TIR-lncRNAs were functionally characterized, three of which were identified as a novel TIR-lncRNA signature for predicting the prognosis of RCC.

Computed tomography-guided cryoablation for adrenal metastases secondary to lung cancer.

OBJECTIVES: The objective of the study was to assess the clinical efficacy of computed tomography (CT)-guided cryoablation as a means to treat adrenal metastasis (AM) secondary to lung cancer. MATERIALS AND METHODS: This study was a single-center retrospective study that analyzed 39 consecutive patients with AM secondary to lung cancer who underwent CT-guided cryoablation in our center. The rates of complete ablation, local recurrence, local recurrence-free survival (RFS), and overall survival (OS) were analyzed. RESULTS: The rates of primary and secondary complete ablation were 94.9% and 100%, respectively, and none of the patients suffered from a hypertensive crisis associated with the treatment. Over the follow-up period, 20.5% of the patients experienced local recurrence, and the median RFS duration was 26 months. The cumulative 1-, 3-, and 5-year local RFS rates in this study were 84.6%, 51.3%, and 5.9%, respectively. Extra-adrenal gland metastases were detected in five patients. Over the course of follow-up, 26 patients died. The mean OS duration was 34 months with cumulative 1-, 3-, and 5-year OS rates of 89.7%, 53.4%, and 8.3%, respectively. Advanced age (P = 0.001), primary adenocarcinoma (P = 0.006), other primary lung cancers (P = 0.038), and primary Stage III lung cancers (P = 0.007) were all found to be independent predictive factors of poor OS in these patients. CONCLUSION: CT-guided cryoablation can be safely and effectively used to control AM secondary to lung cancer, and patients with AM secondary to lung squamous cell carcinoma may be best suited for this form of treatment.

Long Non-Coding RNA GAS5 Suppresses Tumor Progression and Enhances the Radiosensitivity of Prostate Cancer Through the miR-320a/RAB21 Axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) function as a class of significant mediators in prostate cancer (PCa), and this study mainly discussed the molecular mechanism of lncRNA growth arrest-specific 5 (GAS5) in PCa progression and radiosensitivity. MATERIALS AND METHODS: GAS5 and microRNA-320a (miR-320a) levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and migration were severally examined through 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) and transwell assays. PCa cells were treated with X-ray irradiation. Cell survival and apoptosis rate were assayed using colony formation assay and flow cytometry, respectively. The apoptosis-related protein and Rab GTPase 21 (RAB21) protein levels were measured by Western blot. The relation between miR-320a and GAS5 or RAB21 was assessed via the dual-luciferase reporter assay. The effect of GAS5 on radiosensitivity of PCa in vivo was evaluated by xenotransplantation assay. RESULTS: GAS5 was down-regulated in PCa tissues and cells. GAS5 overexpression suppressed cell viability and migration while facilitated radiosensitivity of PCa cells. GAS5 was a molecular sponge of miR-320a. The effects of GAS5 up-regulation on PCa cells were accomplished by sponging miR-320a. MiR-320a targeted RAB21 and GAS5 up-regulated RAB21 expression via targeting miR-320a. RAB21 knockdown reversed the effects of miR-320a inhibition on PCa cells. GAS5 promoted the radiosensitivity of PCa by the miR-320a/RAB21 axis in vivo. CONCLUSION: Collectively, GAS5 restrained tumor development and expedited the radiosensitivity in PCa by the miR-320a/RAB21 axis, which provided a molecular regulatory mechanism of GAS5/miR-320a/RAB21 in PCa development and radioresistance.