Arginase 2 is a Diagnostic and Prognostic Marker for Prostate Cancer and Is Associated with Metabolism.

Objective: Metabolism, a basic need and biochemical process for cell survival and proliferation, is closely connected with the pathogenesis and progression of prostate cancer. Methods: A four-gene signature construct that includes CKM (CKM), CD38, Enoyl Coenzyme A(EHHADH), and Arginase 2(ARG2) was created by bioinformatics. Finally, hub genes were validated by IHC and in vitro experiments. Results: The results showed the AUCs of the logistic regression and neural networks diagnostic model for the diagnosis of two subtypes were 0.920 and 0.936, respectively. The risk score demonstrated by univariable and multivariable Cox analysis is an independent predictive component of the prognostic signature for DFS. According to immunohistochemical analyses, ARG2 and CD38 expression levels were considerably under-expressed, but CKM and EHHADH expression levels were significantly overexpressed. Furthermore, The expression of ARG2 was significantly down-regulated in the late Gleason score. Finally, we found that ARG2 is lowly expressed in prostate cancer cells. Furthermore, based on the effect of ARG2 on the malignant phenotype of PCa in vitro, we also found that ARG2 may be a tumor suppressor that plays an important role in inhibiting proliferation, migration, and invasion. Conclusions: These findings suggest that ARG2 has been tentatively identified as a new target for research into how PCa develops in metabolism and for the development of innovative targeted treatments.

Identification and Validation of a PPP1R12A-Related Five-Gene Signature Associated With Metabolism to Predict the Prognosis of Patients With Prostate Cancer.

BACKGROUND: Prostate cancer (PCa) is the most common malignant male neoplasm in the American male population. Our prior studies have demonstrated that protein phosphatase 1 regulatory subunit 12A (PPP1R12A) could be an efficient prognostic factor in patients with PCa, promoting further investigation. The present study attempted to construct a gene signature based on PPP1R12A and metabolism-related genes to predict the prognosis of PCa patients. METHODS: The mRNA expression profiles of 499 tumor and 52 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. We selected differentially expressed PPP1R12A-related genes among these mRNAs. Tandem affinity purification-mass spectrometry was used to identify the proteins that directly interact with PPP1R12A. Gene set enrichment analysis (GSEA) was used to extract metabolism-related genes. Univariate Cox regression analysis and a random survival forest algorithm were used to confirm optimal genes to build a prognostic risk model. RESULTS: We identified a five-gene signature (PPP1R12A, PTGS2, GGCT, AOX1, and NT5E) that was associated with PPP1R12A and metabolism in PCa, which effectively predicted disease-free survival (DFS) and biochemical relapse-free survival (BRFS). Moreover, the signature was validated by two internal datasets from TCGA and one external dataset from the Gene Expression Omnibus (GEO). CONCLUSION: The five-gene signature is an effective potential factor to predict the prognosis of PCa, classifying PCa patients into high- and low-risk groups, which might provide potential novel treatment strategies for these patients.

Hue-Preserving Saturation Improvement in RGB Color Cube.

This paper proposes a method for improving saturation in the context of hue-preserving color image enhancement. The proposed method handles colors in an RGB color space, which has the form of a cube, and enhances the contrast of a given image by histogram manipulation, such as histogram equalization and histogram specification, of the intensity image. Then, the color corresponding to a target intensity is determined in a hue-preserving manner, where a gamut problem should be taken into account. We first project any color onto a surface in the RGB color space, which bisects the RGB color cube, to increase the saturation without a gamut problem. Then, we adjust the intensity of the saturation-enhanced color to the target intensity given by the histogram manipulation. The experimental results demonstrate that the proposed method achieves higher saturation than that given by related methods for hue-preserving color image enhancement.

LncRNA growth arrest-specific transcript 5 targets miR-21 gene and regulates bladder cancer cell proliferation and apoptosis through PTEN.

The aim of this study was to investigate the mechanism by which growth arrest-specific transcript 5 (GAS5) regulates bladder cancer cells. Bladder cancer samples were collected and tested for experiment. Dual-luciferase reporter assay was used to verify the downstream target genes for GAS5 and miR-21. The expression level of GAS5 was decreased and that of miR-21 was increased, indicating a negative correlation between the two. Patients with high GAS5 level and low miR-21 level had relatively longer survival rates. GAS5 inhibited bladder cancer cells proliferation and promoted apoptosis, and miR-21 had the opposite effects. MiR-21 was a direct target for GAS5, whereas phosphatase and tensin homolog (PTEN) was a direct target gene of miR-21. Low expression of miR-21 could reverse the proliferative and antiapoptotic effects caused by GAS5 silencing. High levels of GAS5 and low levels of miR-21 might be associated with a higher survival rate in bladder cancer patients. GAS5 could exert antiproliferative and proapoptotic effects on bladder cancer cells through miR-21 and PTEN.

Increased expression of immediate early response gene 3 protein promotes aggressive progression and predicts poor prognosis in human bladder cancer.

BACKGROUND: Immediate early response gene 3 (IER3) is a stress-inducible gene, which exerts diverse effects in regulating cell apoptosis and cell cycle. Growing evidence shows that IER3 functions either as an oncogene or a tumor suppressor in various human cancers with a cancer type-dependent manner. However, the involvement of IER3 in human bladder cancer (BCa) has not been elucidated. In the current study, we aimed to investigate the expression pattern and the clinical significance of IER3 in BCa. METHODS: We performed immunohistochemistry analysis to examine the subcellular localization and the expression levels of IER3 protein in 88 BCa specimens obtained from Department of Pathology in Massachusetts General Hospital. The associations of IER3 protein expression with various clinicopathological features and patients' overall survival were statistically evaluated. RESULTS: IER3 protein was mainly expressed in the cytoplasm in bladder cancer cell. Of 88 BCa tissue specimens, 39 (44.3%) showed high expression of IER3 protein and 49 (55.7%) showed low expression. High IER3 protein expression was significantly associated with high pathologic nodal stage (p = 0.018). Kaplan-Meier analysis revealed that the overall survival of BCa patients with overexpression of IER3 protein was shorter than that with low expression (p < 0.01). Multivariate analysis by Cox regression further identified IER3 as an independent prognostic factor of BCa patients (p = 0.010). CONCLUSIONS: Our findings suggest for the first time that the increased expression of IER3 protein may promote the aggressive progression of BCa. Importantly, IER3 may be a potential prognostic marker for BCa patients.

Mitochondrion-associated protein peroxiredoxin 3 promotes benign prostatic hyperplasia through autophagy suppression and pyroptosis activation.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in the senior men and age plays an important role in the initiation and development of BPH. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles such as mitochondria and suppress pyroptosis, a type of cell death that stimulates inflammatory responses and growth of other cells around. Peroxiredoxin 3 (PRDX3) is the only mitochondrion-associated member of peroxiredoxin family enzymes that exert their protective antioxidant role in cells through their peroxidase activity. We hypothesized that PRDX3 may inhibit autophagy to activate pyroptosis to induce growth of prostatic epithelial cells. Here we show that PRDX3 maintained the integrity of mitochondria and its depletion led to an enhancement of oxidative stresses. PRDX3-associated and PRDX3-free mitochondria co-existed in the same cells. PRDX3 expressed at higher levels in prostatic epithelial cells in prostate tissues from BPH patients and BPH-representative cell line than in prostate tissues from healthy donors and a cell line representing normal epithelial cells. PRDX3 suppressed autophagy flux and activated pyroptosis to induce inflammatory responses and stimulate the over-growth of prostate tissues. Therefore, higher levels of PDRX3 in prostatic epithelial cells may promote the initiation and development of BPH through autophagy inhibition and pyroptosis activation.

Decreased expression of TCF12 contributes to progression and predicts biochemical recurrence in patients with prostate cancer.

As a member of helix-loop-helix protein family, transcription factor 12 functions as either an oncogene or a tumor suppressor in various human cancers. However, there are no reports on its involvement in prostate cancer. To investigate clinical relevance of transcription factor 12 in prostate cancer and to evaluate its roles in malignant phenotypes of this cancer in vitro and in vivo, we here examined expression patterns of transcription factor 12 protein in 50 prostate cancer tissue specimens by immunohistochemistry. Then, associations of transcription factor 12 expression with various clinicopathological characteristics and patients' prognosis of prostate cancer were evaluated. Its involvements in cancer cell proliferation, migration, invasion, and tumor growth were determined by in vitro and in vivo experiments. As a result, the positive immunostaining of transcription factor 12 protein was localized in cytoplasm and/or nucleus of prostate cancer cells. Its expression levels were decreased with prostate cancer Gleason score increased. Statistically, the decreased expression of transcription factor 12 protein more frequently occurred in prostate cancer patients with high Gleason score, positive metastasis, prostate-specific antigen failure, and short biochemical recurrence-free survival (all p < 0.05). Importantly, multivariate analysis showed that the status of transcription factor 12 expression was an independent predictor of biochemical recurrence-free survival in prostate cancer. Functionally, enforced expression of transcription factor 12 suppressed cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. In conclusion, transcription factor 12 protein may be a novel molecule which plays a critical role in prostate cancer progression and patients' prognosis, suggesting it might be a promising therapeutic target for prostate cancer therapy.