Associations between genetically predicted concentrations of plasma proteins and the risk of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer-related death in men. Understanding the proteomic landscape associated with PCa risk can provide insights into its molecular mechanisms and pave the way for potential therapeutic interventions. METHODS: A proteome-wide Mendelian randomization (MR) analysis was employed to determine associations between genetically predicted protein concentrations in plasma and PCa risk. From an initial list of 4,364 proteins, significant associations were identified and validated. Multiple sensitivity analyses were also conducted to enhance the robustness of our findings. RESULTS: Of the 4,364 genetically predicted proteins, 308 exhibited preliminary associations with PCa risk. After rigorous statistical refinement, genetically predicted concentrations of 14 proteins showed positive associations with PCa risk, with odds ratios spanning from 1.55 (95% CI 1.28-1.87) for ATG4B to 2.67 (95% CI 1.94-3.67) for HCN1. In contrast, genetically predicted concentrations of ATG7, B2M, MSMB, and TMEM108 demonstrated inverse associations with PCa. The replication analysis further substantiated positive associations for MDH1 and LSM1, and a negative one for MSMB with PCa. A meta-analysis harmonizing primary and replication data mirrored these findings. Furthermore, the MVMR analysis pinpointed B2M and MSMB as having significant associations with PCa risk. CONCLUSION: The genetic evidence unveils a refined set of proteins associated with PCa risk. The findings underscore the potential of these proteins as molecular markers or therapeutic targets for PCa, calling for deeper mechanistic studies and exploration into their translational relevance.

Characterization of Ligand-Receptor Pair in Bladder Cancer Develops a Validated Scoring Model for Prognosis and Treatment Response.

The role of ligand-receptor (LR) pairs in disease progression has been explored in bladder cancer. However, the relationship of LR pairs with cancer prognosis and treatment response remains poorly understood. We characterized the LR pair network and identified three distinct molecular subtypes with distinct biologic features based on the TCGA database (n = 406) and validated in GSE13507 (n = 165) and GSE32894 (n = 224). Three subtypes were compared for differences in patient clinical characteristics, genomic, and transcriptomic features. A multivariate Lasso Cox regression model was applied to construct an LR pairs-based scoring model to stratify the prognostic risk of patients. We demonstrated the high LR. score patients had better responses in chemotherapy, while low LR. score patients may benefit from immune checkpoint blockade (ICB). Collectively, we identified three LR pair-related subtypes associated with prognosis. We constructed and validated a LR pairs-based gene signature, which helps to predict prognosis and differentiate the susceptible population to chemotherapy and immunotherapy in patients with bladder cancer. Among the LR pairs significantly related to prognosis, ANAX1-EGFR axis was found to be potential therapeutic target for treatment of bladder cancer.

Circular RNA circ-0016068 Promotes the Growth, Migration, and Invasion of Prostate Cancer Cells by Regulating the miR-330-3p/BMI-1 Axis as a Competing Endogenous RNA.

Prostate cancer is a common neoplasm worldwide, and the sixth most common cause of cancer-related mortality. Biomarkers for earlier diagnosis and improved treatment alternatives are critical. Circular RNAs (circRNAs) can promote the growth and progression of various cancers; however, prostate cancer-specific circRNAs have not been found. We identified circ-0016068, a circRNA that was expressed more strongly in prostate cancer tumors vs. normal paired tissue, and confirmed its relatively high expression in prostate cancer tissues and cell lines. We also discerned that circ-0016068 promotes the epithelial-to-mesenchymal transition (EMT) and the growth, migration, and invasion of prostate cancer cells in vitro; and promotes the growth and metastasis of tumors in a mouse model of prostate cancer. Moreover, we found that circ-0016068 competes with the B-lymphoma Moloney murine leukemia virus insertion region-1 (BMI-1) for binding to miR-330-3p. In so doing, circ-0016068 sequesters miR-330-3p and frees BMI-1 to enhance the proliferation, migration, and invasion of prostate cancer cells, and the metastasis of xenograft tumors. These results suggest that circ-0016068 may be a promising diagnostic biomarker for early stage prostate cancer and a potential target for novel cancer therapeutics.

Prognostic Value of Genes and Immune Infiltration in Prostate Tumor Microenvironment.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers and the fifth leading cause of cancer-related death in men. Immune responses in the tumor microenvironment are hypothesized to be related to the prognosis of PCa patients; however, no studies are available to confirm the same. In this study, we aimed to explore the potential link between these two factors and identify new biomarkers to estimate the survival rate of PCa patients. METHODS: A total of 490 cases were obtained from The Cancer Genome Atlas (TCGA) database. The gene expression data were analyzed by the ESTIMATE algorithm to evaluate the immune and stromal scores. The survival rate was calculated according to the case-specific clinical data. Enrichment analysis was performed to discover the main biological processes and signaling pathways of immune responses. We further identified and analyzed hub genes in the protein-protein interaction (PPI) network and evaluated their prognostic values. RESULTS: Immune score significantly correlated with immune cell infiltration and overall survival of PCa patients. The genes CXCR4 and GPR183, identified as hub genes in the PPI network, correlated with immune cell infiltration and prognosis of PCa patients. CONCLUSION: CXCR4 and GPR183 participate in immune cell infiltration and function in PCa patients. The immune score, as well as the expression of CXCR4 and GPR183 in prostate cancer tissues, could be potential indexes for the prognosis of prostate cancer.

Long non-coding RNA cartilage injury-related promotes malignancy in bladder cancer.

Recent advances have highlighted the important roles of long non-coding RNAs (lncRNAs) in a number of biological processes, including oncogenesis. However, the function of lncRNA cartilage injury-related (lncRNA-CIR) in bladder cancer progression remains elusive. A novel function for lncRNA-CIR in bladder cancer was identified in the present study. Reverse transcription quantitative polymerase chain reaction, viability, invasion assay and in vivo implantation were used to evaluate the role of lncRNA-CIR. It was identified that the expression of lncRNA-CIR was frequently upregulated in 52 cancerous tissues and selected bladder cancer cell lines. Additionally, upregulating lncRNA-CIR was demonstrated to promote viability and invasion in T24 and SW780 cells, whereas siRNA-mediated lncRNA-CIR-knockdown consistently exhibited the opposite effects. High lncRNA-CIR levels also dictated poor overall survival among patients with bladder cancer. Furthermore, in vivo implantation experiments also supported a tumorigenic function for lncRNA-CIR, as decreasing lncRNA-CIR levels markedly attenuated Ki-67 staining and xenograft tumor growth. Overall, the present study identified a novel function of lncRNA-CIR and indicates that lncRNA-CIR may serve as a potential biomarker for bladder cancer treatment.