Telomerase related molecular subtype and risk model reveal immune activity and evaluate prognosis and immunotherapy response in prostate cancer.

BACKGROUND: Prostate cancer ranks among the six most lethal malignancies worldwide. Telomerase, a reverse transcriptase enzyme, plays a pivotal role in extending cellular telomeres and is intimately associated with cell proliferation and division. However, the interconnection between prostate cancer and telomerase-related genes (TEASEs) remains unclear. METHODS: Somatic mutations and copy number alterations of TEASEs were comprehensively analyzed. Subsequently, the transcripts of prostate cancer patients in TCGA and GEO databases were integrated to delineate new molecular subtypes. Followed by constructing a risk model containing nine characteristic genes through Lasso regression and Cox prognostic analysis among different subtypes. Various aspects including prognosis, tumor microenvironment (TME), landscape of immunity, tumor mutational burden (TMB), stem cell correlation, and median inhibitory concentration amongst different risk groups were compared. Finally, the expression, prognosis, and malignant biological behavior of ZW10 interactor (ZWINT) in vitro was explored. RESULTS: TEASEs exhibited a notably high mutation frequency. Three distinct molecular subtypes and two gene subclusters based on TEASEs were delineated, displaying significant associations with prognosis, immune function regulation, and clinical characteristics. Low-risk patients demonstrated superior prognosis and better response to immunotherapy. Conversely, high-risk patients exhibited higher TMB and stronger stem cell correlations. It was also found that the patients' sensitivity to chemotherapy agents was impacted by the risk score. Finally, ZWINT's potential as a novel diagnostic and prognostic biomarker for prostate cancer was validated. CONCLUSIONS: TEASEs play a pivotal role in modulating immune regulation and immunotherapeutic responses, thereby significantly impacting the diagnosis, prognosis, and treatment strategies for affected patients.

Impact of positive surgical margin location and perineural invasion on biochemical recurrence in patients undergoing radical prostatectomy.

OBJECTIVE: To estimate the prognostic value of positive surgical margins (PSM) location and perineural invasion (PNI) for biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP). METHODS: All men with prostate cancer (PCa) who received RP in the second hospital of Tianjin Medical University from 2014 to 2018 were retrospectively identified. All patients met the following criteria: no neoadjuvant or adjuvant treatment, absence of lymph node invasion, or distant metastasis confirmed by surgery or imaging. Comparisons were made between cases with only apex positive (AM), isolated nonapical positive (OM), multiple positive (MM), and negative surgical margins (NSM). Patients were also subdivided according to the Gleason score and pathological tumor stage for analysis. RESULTS: A total of 416 patients available for analysis, of which 132 (31.7%) were PSM, 43 were AM, 37 were OM, and 52 were MM at a median follow-up of 27 months. The PNI was in 30.5% of patients. BCR occurred in 22.6% of patients during follow-up. Both AM and MM were noticed to be independent predictors of BCR with a hazard ratio of 4.192 (95% CI 2.185-8.042; p < 0.001) and 2.758 (95% CI 1.559-4.880; p < 0.001), respectively, when compared to NSM. Though the correlation was significant in univariate analysis, PNI was not an independent risk factor for BCR (p = 0.369). Subgroup analyses suggested that MM was not particularly predictive for BCR in the Gleason score < 8. The hole Cox regression model for the C-index was 0.843 CONCLUSIONS: PSM location was a significant independent predictor of BCR in PCa, especially in patients with AM or MM, while PNI is a non-independent risk factor. Compared with other locations, AM has a higher BCR risk.

Nucleobindin 2 expression is an independent prognostic factor for clear cell renal cell carcinoma.

AIMS: Nucleobindin 2 (NUCB2) has been reported to play an important role in both tumorigenesis and cancer progression. This study aimed to examine the clinical significance of NUCB2 expression in clear cell renal cell carcinoma (ccRCC). METHODS AND RESULTS: The expression level of NUCB2 and its correlation with clinicopathological parameters was analysed in 188 ccRCC tissues and adjacent non-cancerous tissues by immunohistochemistry. Samples from eight ccRCC patients were examined by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between NUCB2 expression and the prognosis of ccRCC patients. The expression level of NUCB2 was found to be significantly higher in ccRCC tumours compared to adjacent non-cancerous tissues using immunohistochemistry, Western blotting and qRT-PCR. Moreover, high NUCB2 tumour expression was associated with high T stage and metastasis and shorter overall survival. Univariate and multivariate analysis confirmed that NUCB2 was an independent prognostic factor for overall survival. CONCLUSIONS: Our results show that NUCB2 plays an important role in tumorigenesis and progression and is a potential molecular biomarker for the diagnosis and targeted therapy of ccRCC.

High expression of nucleobindin 2 mRNA: an independent prognostic factor for overall survival of patients with prostate cancer.

Nucleobindin 2 (NUCB2) has been demonstrated to play critical roles in tumorigenesis and tumor development of breast cancer. The expression change of nucleobindin 2 at mRNA level in prostate cancer (PCa) tissues compared with adjacent benign prostate tissues was detected by using real-time quantitative reverse transcriptase-polymerase chain reaction analysis in our previous study. The data suggests that NUCB2 is a cancer-related gene associated with the aggressive progression and biochemical recurrence-free survival predictor of PCa patients. However, the correlation between the expression of the NUCB2 mRNA and the overall survival of patients with PCa was not analyzed. Thus, the association of NUCB2 mRNA expression with overall survival of PCa patients was analyzed in this study. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between NUCB2 mRNA expression and prognosis of PCa patients. The Kaplan-Meier survival analysis showed that the high expression of NUCB2 was related to the poor overall survival of patients with PCa. Multivariate Cox analysis showed that NUCB2 mRNA was an independent prognostic factor for overall survival of patients with PCa. In conclusion, we demonstrated that high NUCB2 mRNA expression correlated with poor overall survival in patients with PCa.

The CCND1 G870A polymorphism and susceptibility to bladder cancer.

Published studies on the association between cyclin D1 (CCND1) G870A polymorphism and bladder cancer risk have yielded conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. All eligible studies of G870A polymorphism and bladder cancer risk were collected from the PubMed and the Cochrane Library. Statistical analyses were performed by Review Manager 5.0 and Stata 11.0. Significant association between G870A polymorphism and bladder cancer susceptibility was found under recessive model in overall population (OR = 1.21, 95% CI 1.01-1.45, P = 0.04). When stratifying for the race, our analysis suggested that CCND1 G870A was associated with bladder cancer risk in Asians when using homogeneous codominant (OR = 1.72, 95% CI 1.34-2.20, P < 0.0001), recessive (OR = 1.46, 95% CI 1.21-1.77, P < 0.0001), dominant (OR = 1.36, 95% CI 1.10-1.69, P = 0.004), and allelic models (OR = 1.30, 95% CI 1.15-1.47, P < 0.0001) to analyze the data. However, no significant associations were found in Caucasians. After stratifying the studies by control source, G870A polymorphism was significantly associated with bladder cancer risk under recessive model (OR = 1.31, 95% CI 1.03-1.67, P = 0.03) in hospital-based case-control studies, but not in population-based case-control studies. This meta-analysis suggested that G870A polymorphism most likely contributes to increased susceptibility to bladder cancer in the overall population, hospital-based case-control studies, and Asians.

Protein tyrosine kinase 7 (PTK7) as a predictor of lymph node metastases and a novel prognostic biomarker in patients with prostate cancer.

Protein tyrosine kinase 7 (PTK7) has been studied in various tumors, but its role in prostate cancer remains unknown. This study is aimed to investigate the prognostic and predictive significance of PTK7 in patients with prostate cancer. PTK7 expression was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis in 20 pairs of benign prostatic hyperplasia specimens and prostate cancer specimens. Then, we examined the immunohistochemical expression of PTK7 in 180 prostate cancer specimens and evaluated its clinical significances. Elevated PTK7 expression was significantly associated with lymph node metastases, seminal vesicle invasion, prostate cancer stage, the higher preoperative prostate-specific antigen, the higher Gleason score, angiolymphatic invasion, and biochemical recurrence. The results revealed that the overexpression of PTK7 in prostate cancer was an independent prognostic factor for poor overall survival and biochemical recurrence-free survival. The present data provide evidence that PTK7 predicts lymph node metastasis and poor overall survival and biochemical recurrence-free survival, highlighting its potential function as a therapeutic target for prostate cancer.

Inflammatory cytokine profiles in erectile dysfunction: a bidirectional Mendelian randomization.

Objectives: Inflammatory cytokines (ICs) play an important role in erectile dysfunction (ED). Previous studies have demonstrated that most ED patients have high levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). The causality between 41 ICs and ED is investigated using the Mendelian randomization (MR) approach. Methods: Single nucleotide polymorphisms (SNPs) exposure data of 41 ICs came from a genome-wide association study (GWAS) of 8293 subjects. At the same time, the FINNGEN R9 database provided the ED outcome data containing 2205 ED patients and 164104 controls. MR-Egger (ME), inverse variance weighting (IVW), and weighted median (WM) were applied to conduct the MR study and IVW was taken as the main criterion. Results: From a genetic perspective, the increase of interferon-inducible protein-10 (IP-10) level significantly increased the risk of ED (P=0.043, odds ratio (OR)=1.269, 95% confidence interval (95%CI): 1.007-1.600), while the increase of interleukin-1 receptor antagonist (IL-1RA) markedly decreased the risk of ED (P=0.037, OR=0.768, 95%CI: 0.600-0.984). Meanwhile, IP-10 (p=0.099) and IL-1RA (p=0.135) failed to demonstrate causality in reverse MR analysis. Conclusions: Changes in ICs levels will significantly affect the risk of ED, especially IP-10 as a risk component for ED and IL-1RA as a protective component for ED. In the future, we can achieve targeted treatment and prevention of ED by intervening with specific inflammatory factors.

Association between insulin receptor substrate 1 Gly972Arg polymorphism and cancer risk.

Epidemiological studies investigating the association between the insulin receptor substrate 1 (IRS1) gene Gly972Arg (rs1801278) polymorphism and various carcinomas risk reported conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. A comprehensive search was conducted to identify all eligible studies of IRS1 Gly972Arg polymorphism and cancer risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations. A total of 16 independent studies, including 11,776 cases and 11,654 controls, were identified. When all studies were pooled, we found a significant association between IRS1 Gly972Arg polymorphism and increased cancer risk under dominant model (OR = 1.16, 95 %CI = 1.04-1.30, P = 0.007) and allelic model (OR = 1.16, 95 %CI = 1.02-1.30, P = 0.02). In subgroup analysis based on cancer type, increased cancer risk was found in ovarian cancer (dominant: OR = 1.55, 95 %CI = 1.17-2.05, P = 0.002; allelic: OR = 1.55, 95 %CI = 1.19-2.01, P = 0.001), breast cancer (allelic: OR = 1.12, 95 %CI = 1.00-1.26, P = 0.05), and other cancers (allelic: OR = 1.31, 95 %CI = 1.00-1.71, P = 0.05). When stratified by study types, significant associations were observed in both cohort studies (dominant: OR = 1.25, 95 %CI = 1.06-1.47, P = 0.007; allelic: OR = 1.25, 95 %CI = 1.07-1.46, P = 0.005) and case-control studies (dominant: OR = 1.15, 95 %CI = 1.01-1.31, P = 0.04). In the subgroup analyses by ethnicity, significantly increased cancer risk was suggested among both Caucasians (dominant: OR = 1.13, 95 %CI = 1.02-1.26, P = 0.02; allelic: OR = 1.13, 95 %CI = 1.03-1.25, P = 0.01) and mixed population (dominant: OR = 1.22, 95 %CI = 1.01-1.46, P = 0.04). Our investigations demonstrate that IRS1 Gly972Arg polymorphism was associated with an increased risk of cancer, and additional well-designed studies are warranted to validate these findings.

Lack of association between COMT Val158Met polymorphism and prostate cancer susceptibility.

BACKGROUND: The relationship of prostate cancer (PCa) with the presence of catechol-O-methyltransferase (COMT) genetic polymorphism Val158Met (158G/A) has been reported with inconsistent results. The objective of this study was to quantitatively evaluate the association between Val158Met polymorphism and PCa susceptibility. METHODS: Two investigators independently searched Medline and the Cochrane Library up to July 18, 2012. Pooled odds ratio and 95% confidence interval were calculated using a fixed or random-effects model. Statistical analysis was performed with Review Manage 5.0 and Stata 11. RESULTS: Of the 7 case-control studies selected for this meta-analysis, a total of 2,292 PCa cases and 2,485 controls were included. The combined results based on all studies suggested that Val158Met was not associated with PCa risk under all genetic models. When stratifying for race, no noteworthy associations were observed in Asians or Caucasians. CONCLUSION: This meta-analysis suggests that COMT Val158Met polymorphism might not be a risk factor for PCa risk. However, further well-designed studies are required to confirm our findings.

CHMP4C as a novel marker regulates prostate cancer progression through cycle pathways and contributes to immunotherapy.

Background: CHMP4C is one of the charged multivesicular protein (CHMP), and is involved in the composition of the endosomal sorting complex required for transport III (ESCRT-III), facilitating the necessary separation of daughter cells. CHMP4C has been proposed to be involved in the progression of different carcinomas. However, the value of CHMP4C in prostate cancer has not yet been explored. Prostate cancer is the most frequently occurring malignancy among male and remains a leading cause of deaths in cancers. So far, clinical therapy of prostate cancer is more inclined to molecular classification and specific clinical treatment and research. Our study investigated the expression and clinical prognosis of CHMP4C and explored its potential regulatory mechanism in prostate cancer. The immune status of CHMP4C in prostate cancer and relative immunotherapy were then analyzed in our study. Based on CHMP4C expression, a new subtype of prostate cancer was established for precision treatment. Methods: We studied the expression of CHMP4C and relative clinical outcome using the online databases TIMER, GEPIA2, UALCAN, and multiple R packages. Meanwhile, the biological function, immune microenvironment and immunotherapy value of CHMP4C in prostate cancer were further explored on the R software platform with different R packages. Then we performed qRT-PCR, Western Blotting, transwell, CCK8, wound healing assay, colony formation assay and immunohistochemistry to verify the expression of CHMP4C, carcinogenesis and potential regulatory mechanisms in prostate cancer. Results: We found that the expression of CHMP4C is significant in prostate cancer and the high expression of CHMP4C represents a poor clinical prognosis and malignant progression of prostate cancer. In subsequent vitro validation, CHMP4C promoted the malignant biological behavior of prostate cancer cell lines by adjusting the cell cycle. Based on CHMP4C expression, we established two new subtypes of prostate cancer and found that low CHMP4C expression has a better immune response while high CHMP4C expression was more sensitive to paclitaxel and 5-fluorouracil. Above findings revealed a new diagnostic marker for prostate cancer and facilitated the subsequent precise treatment of prostate cancer.

Experimental validation and pan-cancer analysis identified COL10A1 as a novel oncogene and potential therapeutic target in prostate cancer.

BACKGROUND: Type X collagen (COL10) is a homologous trimeric non-fibrillar collagen found in the extracellular matrix of human tissues, and it exhibits a distinctive white appearance. Type X collagen α1 chain (COL10A1) is a specific cleaved fragment of type X collagen. However, the expression, prognostic significance, clinicopathological attributes and immune-related associations of COL10A1 in prostate cancer as well as in pan-cancer contexts remain poorly understood. METHODS: Using bioinformatic analysis of data from the most recent databases (TCGA, GTEx and GEO databases), we have extensively elucidated the role played by COL10A1 in terms of its expression patterns, prognostic implications, and immune efficacy across a pan-cancer spectrum. Subsequently, the biological functions of COL10A1 in prostate cancer were elucidated by experimental validation. RESULTS: Our findings have confirmed that COL10A1 was highly expressed in most cancers and was associated with poorer prognosis in cancer patients. Immune correlation analysis of COL10A1 in various cancers showed its significant correlation with Tumor mutational burden (TMB), microsatellite instability (MSI) and immune cell infiltration. In addition, knockdown of COL10A1 in prostate cancer resulted in a substantial reduction in the proliferation, migration, and invasive potential of prostate cancer cells. CONCLUSION: Our pan-cancer analysis of COL10A1 gene provided novel insights into its pivotal role in cancer initiation, progression, and therapeutic implications, underscoring its potential significance in prognosis and immunotherapeutic interventions for cancer, particularly prostate cancer.

Association between COX-2 rs2745557 polymorphism and prostate cancer risk: a systematic review and meta-analysis.

BACKGROUND: Evidence is accumulating that chronic inflammation may have an important role in prostate cancer (PCa). The COX-2 polymorphism rs2745557 (+202 C/T) has been extensively investigated as a potential risk factor for PCa, but the results have thus far been inconclusive. This meta-analysis was performed to derive a more precise estimation of the association. METHODS: A comprehensive search was conducted to identify all case-control studies of COX-2 rs2745557 polymorphism and PCa risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) give a sense of the precision of the estimate. Statistical analyses were performed by Review Manage, version 5.0 and Stata 10.0. RESULTS: A total of 8 available studies were considered in the present meta-analysis, with 11356 patients and 11641 controls for rs2745557. When all groups were pooled, there was no evidence that rs2745557 had significant association with PCa under co-dominant, recessive, over-dominant, and allelic models. However, our analysis suggested that rs2745557 was associated with a lower PCa risk under dominant model in overall population (OR=0.85, 95%CI=0.74-0.97, P=0.02). When stratifying for race, there was a significant association between rs2745557 polymorphism and lower PCa risk in dominant model comparison in the subgroup of Caucasians (OR=0.86, 95%CI=0.75-0.99, P=0.04), but not in co-dominant, recessive, over-dominant and allelic comparisons. CONCLUSION: Based on our meta-analysis, COX-2 rs2745557 was associated with a lower PCa risk under dominant model in Caucasians.

The interleukin-6 -174G/C polymorphism and prostate cancer risk: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis was undertaken to integrate previous findings and summarize the effect size of the association of interleukin-6 (IL-6) genetic polymorphism -174G/C with susceptibility to prostate cancer (PCa). METHODS: All eligible studies of IL-6 -174G/C polymorphism and PCa risk were collected from the following electronic databases: PubMed and the Cochrane Library, with the last report up to June 1, 2011. Statistical analyses were performed by Review Manage version 5.0 and Stata 10.0. RESULTS: A total of 7 independent studies, including 9,959 cases and 12,361 controls, were identified. When all studies were pooled, we did not detect a significant association of -174G/C polymorphism with PCa risk. When stratifying for race, similar results were obtained; evidence of a significant relation was absent in both Caucasians and the mixed population. After stratifying the studies by study types, -174G/C polymorphism was significantly associated with PCa risk when examining the contrast of CC + GC versus GG (OR = 1.44, 95% CI = 1.05-1.98, p = 0.03) in cohort studies but not in case-control studies. CONCLUSIONS: Our review suggest that -174G/C polymorphism is associated with an increased PCa risk in two cohort studies from one article. Additional well-designed studies are warranted to validate these findings.

[Correlation of histological prostatitis with PSA, prostate volume, PSAD, IPSS, Qmax and PVR in BPH patients].

OBJECTIVE: To explore the correlation of histologically proven prostatitis with the level of prostate specific antigen (PSA), prostate volume, PSA density (PSAD), international prostate symptom score (IPSS), maximum flow rate (Qmax) and post-void residual volume (PVR) in men with symptoms of benign prostate hyperplasia (BPH). METHODS: Totally 673 patients surgically treated for BPH were divided into Groups A and B in accordance with histological findings, the former including those with histological prostatitis, and the latter without it. Comparisons were made between the two groups in the PSA level, prostate volume, PSAD, IPSS, Qmax and PVR. RESULTS: The PSA level, prostate volume, IPSS and PVR were significantly higher in Group A ([5.64 +/- 2.48] microg/L, [43.66 +/- 13.11] ml, 24.72 +/- 5.39 and [124.90 +/- 49.80] ml) than in B ([4.97 +/- 1.99] microg/L, [40.41 +/- 11.44] ml, 23.40 +/- 6.21 and [112.73 +/- 50.03] ml) (P<0.05), while Qmax markedly lower in the former ([6.94 +/- 3.23] ml/s) than in the latter ([7.75 +/- 3.52] ml/s) (P<0.05), but PSAD showed no statistically significant difference between the two groups (0.129 +/- 0.048 vs 0.123 +/- 0.034, P>0.05). CONCLUSION: Histological prostatitis can significantly increase the PSA level, prostate volume, IPSS and PVR, and reduce the Qmax of the patient, but is not correlated with PSAD. It is an important factor influencing the clinical progression of BPH.

MiR-96-5p induced NDRG1 deficiency promotes prostate cancer migration and invasion through regulating the NF-κB signaling pathway.

OBJECTIVE: The N-myc downstream-regulated gene 1 (NDRG1) has been discovered as a significant gene in the progression of cancers. However, the regulatory mechanism of NDRG1 remained obscure in prostate cancer (PCa). METHODS: The miR-96-5p and NDRG1 expression levels were evaluated in PCa cell lines, prostate tissues, and validated public databases by real-time PCR, western blot analysis, and immunohistochemistry. The function of miR-96-5p and NDRG1 were investigated by wound healing and transwell assays in vitro, and mouse xenograft assay in vivo. The candidate pathway regulated by NDRG1 was conducted by the next-generation gene sequencing technique. Immunofluorescence and luciferase assay was used to detect the relation between miR-96-5p, NDRG1, and NF-κB pathway. RESULTS: Overexpressing NDRG1 suppresses the migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, and inhibits metastasis in vivo. Moreover, miR-96-5p contributes to NDRG1 deficiency and promotes PCa cell migration and invasion. Furthermore, NDRG1 loss activates the NF-κB pathway, which stimulates p65 and IKBa phosphorylation and induces EMT in PCa. CONCLUSIONS: MiR-96-5p promotes the migration and invasion of PCa by targeting NDRG1 and regulating the NF-κB pathway.

Predicting Prognosis and Distinguishing Cold and Hot Tumors in Bladder Urothelial Carcinoma Based on Necroptosis-Associated lncRNAs.

Background: In reference to previous studies, necroptosis played an important role in cancer development. Our team decided to explore the potential prognostic values of long non-coding RNAs (lncRNAs) associated with necroptosis in bladder urothelial carcinoma (BLCA) and their relationship with the tumor microenvironment (TME) and the immunotherapeutic response for accurate dose. Methods: To obtain the required data, bladder urothelial carcinoma transcriptome data were searched from Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/). We used co-expression analysis, differential expression analysis, and univariate Cox regression to screen out prognostic lncRNAs associated with necroptosis in BLCA. Then the least absolute shrinkage and selection operator (LASSO) was conducted to construct the necroptosis-associated lncRNAs model. Based on this model, we also performed the Kaplan-Meier analysis and time-dependent receiver operating characteristics (ROC) to estimate the prognostic power of risk score. Multivariate and univariate Cox regression analysis were performed to build up a nomogram. Calibration curves, and time-dependent ROC were also conducted to evaluate nomogram. Principal component analysis (PCA) revealed a difference between high- and low-risk groups. In addition, we explored immune analysis, gene set enrichment analyses (GSEA), and evaluation of the half-maximal inhibitory concentration (IC50) in constructed model. Finally, the entire samples were divided into three clusters based on model of necroptosis-associated lncRNAs to further compare immunotherapy in cold and hot tumors. Results: A model was built up based on necroptosis-associated lncRNAs. The model revealed good consistence between calibration plots and prognostic prediction. The area of 1-, 3-, and 5-year OS under the ROC curve (AUC) were 0.707, 0.679, and 0.675. Risk groups could be helpful for systemic therapy due to the markedly diverse IC50 between risk groups. To our delight, clusters could effectively identify cold and hot tumors, which would be beneficial to accurate mediation. Clusters 2 and 3 were considered the hot tumor, which was more sensitive to immunotherapeutic drugs. Conclusions: The outcomes of our study suggested that necroptosis-associated lncRNAs could effectively predict patients with BLCA prognosis, which may be helpful for distinguishing the cold and hot tumors and improving individual treatment of BLCA.

Cuproptosis-Associated lncRNA Establishes New Prognostic Profile and Predicts Immunotherapy Response in Clear Cell Renal Cell Carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) accounts for 80% of all kidney cancers and has a poor prognosis. Recent studies have shown that copper-dependent, regulated cell death differs from previously known death mechanisms (apoptosis, ferroptosis, and necroptosis) and is dependent on mitochondrial respiration (Tsvetkov et al., Science, 2022, 375 (6586), 1254-1261). Studies also suggested that targeting cuproptosis may be a novel therapeutic strategy for cancer therapy. In ccRCC, both cuproptosis and lncRNA were critical, but the mechanisms were not fully understood. The aim of our study was to construct a prognostic profile based on cuproptosis-associated lncRNAs to predict the prognosis of ccRCC and to study the immune profile of clear cell renal cell carcinoma (ccRCC). Methods: We downloaded the transcriptional profile and clinical information of ccRCC from The Cancer Genome Atlas (TCGA). Co-expression network analysis, Cox regression method, and least absolute shrinkage and selection operator (LASSO) method were used to identify cuproptosis-associated lncRNAs and to construct a risk prognostic model. In addition, the predictive performance of the model was validated and recognized by an integrated approach. We then also constructed a nomogram to predict the prognosis of ccRCC patients. Differences in biological function were investigated by GO, KEGG, and immunoassay. Immunotherapy response was measured using tumor mutational burden (TMB) and tumor immune dysfunction and rejection (TIDE) scores. Results: We constructed a panel of 10 cuproptosis-associated lncRNAs (HHLA3, H1-10-AS1, PICSAR, LINC02027, SNHG15, SNHG8, LINC00471, EIF1B-AS1, LINC02154, and MINCR) to construct a prognostic prediction model. The Kaplan-Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. The cuproptosis-associated lncRNA model had higher diagnostic efficiency compared to other clinical features. The analysis of Immune cell infiltration and ssGSEA further confirmed that predictive features were significantly associated with the immune status of ccRCC patients. Notably, the superimposed effect of patients in the high-risk group and high TMB resulted in shorter survival. In addition, the higher TIDE scores in the high-risk group suggested a poorer outcome for immune checkpoint blockade response in these patients. Conclusion: The ten cuproptosis-related risk profiles for lncRNA may help assess the prognosis and molecular profile of ccRCC patients and improve treatment options, which can be further applied in the clinic.

The hOGG1 Ser326Cys polymorphism and prostate cancer risk: a meta-analysis of 2584 cases and 3234 controls.

BACKGROUND: Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys (rs1052133) has been implicated to alter the risk of prostate cancer, but the results are controversial. METHODS: Two investigators independently searched the Medline, and Cochrane Library up to June 7, 2011. Summary odds ratios (OR) and 95% confidence interval (CI) for Ser326Cys polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage, version 5.0 and Stata 10.0. RESULTS: A total of 8 independent studies, including 2584 cases and 3234 controls, were identified. Our analysis suggested that Ser326Cys was not associated with prostate cancer risk in overall population. In the subgroup analysis, we detected the significant association between Ser326Cys polymorphism and decreased prostate risk in mixed population under additive model (OR = 0.67, 95% CI = 0.50-0.90, P = 0.007), recessive model (OR = 0.68, 95% CI = 0.51-0.91, P = 0.008), and Cys allele versus Ser allele (OR = 0.88, 95% CI = 0.78-0.98, P = 0.02). Subanalysis on Caucasian subjects demonstrated that Ser326Cys was not associated with prostate cancer risk. CONCLUSION: This meta-analysis showed the evidence that hOGG1 Ser326Cys polymorphism was associated with a decreased risk of prostate cancer development in mixed populations.

CircGNG4 Promotes the Progression of Prostate Cancer by Sponging miR-223 to Enhance EYA3/c-myc Expression.

Patients diagnosed with prostate cancer often have a poor prognosis and limited treatment options, as the specific pathogenesis remains to be elucidated. Circular RNA (circRNA) is a type of non-coding RNA that interacts with microRNA (miRNA/miR) and transcription factors to regulate gene expression. However, little is known about specific circRNAs that serve roles in the pathogenesis of prostate cancer. Findings of the present study confirmed that circRNA G protein subunit γ 4 (circGNG4) was upregulated in prostate cancer tissues and cell lines. Knockdown of circGNG4 inhibited the malignant behavior of prostate cancer cells. Furthermore, bioinformatics were used to predict targeting interactions between circGNG4 or miR-223 and EYA transcriptional coactivator and phosphatase 3 (EYA3)/c-Myc mRNA. miR-223 inhibited the malignant behavior of prostate cancer cells, while EYA3/c-Myc had the opposite effect. circGNG4 enhanced the expression of EYA3/c-Myc by sponging miR-223 to promote the growth of prostate cancer tumors in vivo. In conclusion, the circGNG4/miR-223/EYA3/c-Myc regulatory pathway promoted the malignant progression of prostate cancer. The results of the present study may provide potential new targets for the diagnosis or treatment of prostate cancer.

Loss of miR-516a-3p mediates upregulation of ABCC5 in prostate cancer and drives its progression.

To gain a comprehensive understanding of whether ABCC5 can regulate prostate cancer (PCa) progression, we performed microarray data analyses and identified that ABCC5 was drastically increased in primary PCa relative to normal samples, metastatic PCa relative to primary PCa, and castration-resistant PCa relative to hormone naïve PCa, respectively. Multivariate Cox regression analysis suggested that ABCC5 overexpression in PCa was an independent prognostic factor for both poor biochemical recurrence-free and overall survival. We demonstrated that ABCC5 knockdown significantly inhibits PCa cell proliferation, migration, and invasion in vitro and suppresses tumor growth and metastasis in vivo. We also demonstrated that miR-516a-3p was significantly downregulated in PCa. We finally demonstrated that ABCC5 was a direct target of miR-516a-3p. miR-516a-3p overexpression can phenotypically copy ABCC5 knockdown-induced phenotypes, whereas forced expression of ABCC5 can drastically reverse the inhibitory effects of miR-516a-3p. miR-516a-3p may modulate the sensitivity of cancer cells to adriamycin and docetaxel by targeting ABCC5 with important implications in the design of new therapeutic agents. Taken together, our results indicated that loss of miR-516a-3p expression and thus uncontrolled ABCC5 upregulation might drive PCa progression and influence chemosensitivity.