Background: Ferroptosis is a newly found non-apoptotic forms of cell death that plays an important role in tumors. However, the prognostic value of ferroptosis-related genes (FRG) in bladder cancer (BLCA) have not been well examined. Methods: FRG data and clinical information were collected from The Cancer Genome Atlas (TCGA). Then, significantly different FRGs were investigated by functional enrichment analyses. The prognostic FRG signature was identified by univariate cox regression and least absolute shrinkage and selection operator (LASSO) analysis, which was validated in TCGA cohort and Gene Expression Omnibus (GEO) cohort. Subsequently, the nomogram integrating risk scores and clinical parameters were established and evaluated. Additionally, Gene Set Enrichment Analyses (GSEA) was performed to explore the potential molecular mechanisms underlying our prognostic FRG signature. Finally, the expression of three key FRGs was verified in clinical specimens. Results: Thirty-two significantly different FRGs were identified from TCGA–BLCA cohort. Enrichment analyses showed that these genes were mainly related to the ferroptosis. Seven genes (TFRC, G6PD, SLC38A1, ZEB1, SCD, SRC, and PRDX6) were then identified to develop a prognostic signature. The Kaplan–Meier analysis confirmed the predictive value of the signature for overall survival (OS) in both TCGA and GEO cohort. A nomogram integrating age and risk scores was established and demonstrated high predictive accuracy, which was validated through calibration curves and receiver operating characteristic (ROC) curve [area under the curve (AUC) = 0.690]. GSEA showed that molecular alteration in the high- or low-risk group was closely associated with ferroptosis. Finally, experimental results confirmed the expression of SCD, SRC, and PRDX6 in BLCA. Conclusion: Herein, we identified a novel FRG prognostic signature that maybe involved in BLCA. It showed high values in predicting OS, and targeting these FRGs may be an alternative for BLCA treatment. Further experimental studies are warranted to uncover the mechanisms that these FRGs mediate BLCA progression.

Background: Stanniocalcin-1 (STC1) is a well-studied oncogene that promotes different types of cancer progression. However, the expression status of STC1, the values of STC1 on prognosis, and its immune characteristic in bladder cancer (BLCA) have not been well examined. Methods: The expression of STC1 and its clinicopathological as well as immune characteristics in BLCA samples were firstly identified in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Immunohistochemistry (IHC) performed on the tissue microarray (TMA) slide was further used to validate the expression of STC1 and its relationship with immune features in 16 non-muscle invasive bladder cancer (NMIBC) samples and 42 muscle invasive bladder cancer (MIBC) samples. Results: The expression of STC1 was upregulated in higher stage BLCA. High STC1 expression also predicted poor prognosis in BLCA. Subsequently, the TMA validated the expression and prognostic value of STC1 in BLCA. Bioinformatics analysis demonstrated that STC1 and common immune checkpoints as well as immune markers of various immune cells were positively correlated in TCGA. In addition, IHC data from the TMA further validated that tumor cells with higher STC1 level tended to express higher PDL1 as well as increased infiltration of CD3+ T cells. Conclusion: To our knowledge, this is the first comprehensive study that investigates the clinical and immune characteristics of STC1 in BLCA. It may provide new insight into the function of STC1 in regulating tumor immune microenvironment. Further studies are warranted to uncover the potential mechanisms that mediate STC1 expression and tumor immunity in BLCA.

Background: Prostate cancer (PC) ranks as the fifth deadliest tumor in the world and has been regarded as a serious threat for the life and health of middle-aged and elderly men. Some studies have shown that LINC00861 regulated the anti-tumor immune response, and may have a certain impact on tumor immunotherapy. Therefore, to explore the related role of LINC00861 in PC, we detected the expression of LINC00861 in PC, and regulated the expression of LINC00861 after confirming its expression. This study aimed to explore the potential of LINC00861 in promoting the immunity of cytotoxic T cells and influencing the biological behavior of PC cells and tumor growth by regulating programmed cell death 1 ligand 1 (PD-L1). Methods: Expression of LINC00861 and PD-L1 was detected in 10 cases of PC and adjacent tissues. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis was performed to assess the expression level of LINC00861 in cancer cells. Cell lines with differential expression were selected for interference and overexpression of LINC00861, followed by grouping. The vitality of PC cells was observed, and measurements were taken for cell proliferation, migration, invasion, PD-L1, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and expression of inflammatory factors such as Interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α in the cells. To establish the subcutaneous PC tumor model, PC cells from each group were subcutaneously implanted in the right flank of BALB/c mice using 100 μL of phosphate-buffered saline (PBS). Mouse tumor tissues were collected to observe tumor size, assess tumor-infiltrating lymphocytes, and evaluate the infiltration of cytotoxic T cells (CD3⁺ and CD8⁺). Results: In PC tissues and cells, PC-3 cells were selected for subsequent experiments through cell screening. Successful transfection of LINC00861 inhibition and overexpression vectors was achieved in PC cells. Inhibiting the expression of LINC00861 upregulated the expression of PD-L1, enhanced cell growth vitality, proliferation, migration, invasion, and cytokine production capabilities, and reduced apoptosis. Overexpression reversed these effects. In in vivo experiments, inhibiting LINC00861 expression resulted in rapid tumor growth, accompanied by increased tumor volume and dense tumor tissue cells. Overexpression of LINC00861 produced the opposite results for these effects. The findings also indicated that inhibiting LINC00861 led to a significant increase in PD-L1 expression in tumor tissues and a significant decrease in CD3⁺ T and CD8⁺ T levels (p < 0.05). When LINC00861 was overexpressed, PD-L1 levels were reduced, while CD3⁺ T and CD8⁺ T levels were improved. Conclusions: LINC00861 is down-regulated in PC tissues. The inhibition of LINC00861 increases the expression of PD-L1, inhibits cytotoxic T cells immunity, and enhances the growth of PC cells and tumor growth and metastasis. Overexpression inhibits the development of PC.