TET3 is expressed in prostate cancer tumor-associated macrophages and is associated with anti-androgen resistance.

PURPOSE: The aim of this study is to investigate the expression of TET3 in prostate cancer and its effect on the efficacy of anti-androgen therapy (ADT). METHODS: The expression of TET3 in 1965 cases of prostate cancer and 493 cases of normal prostate tissues were analyzed. The CIBERSORT algorithm evaluated the abundance of 22 tumor-infiltrating immune cells in 497 prostate cancers. Subsequently, the expression of TET3 in prostate cancer TAMs was analyzed using 21,292 cells from single-cell RNA sequencing (scRNAseq). In addition, the trajectory of the differentiation process was reconstructed based on pseudotime analysis. Sensitivity prediction of prostate cancers to ADT was evaluated based on GDSC2 and CTRP databases. Another dataset GSE111177 was employed for further analysis. RESULTS: TET3 was over-expressed in prostate cancer, and the expression of TET3 in metastatic prostate cancer was higher than that in non-metastatic prostate cancer. The scRNAseq analysis of prostate cancer showed that TET3 was mainly expressed in TAM. TET3 expressed in early and active TAMs, with the activation of signaling pathways such as energy metabolism, cell communication, and cytokine production. Prostate cancer in TET3 high expression group was more sensitive to ADT drugs such as Bicalutamide and AZD3514, and was also more sensitive to chemotherapy drugs such as Cyclophosphamide, Paclitaxel, and Vincristine, and MAPK pathway inhibitors of Docetaxel and Dabrafenib. CONCLUSIONS: The efficacy of ADT in prostate cancer is related to the expression of TET3 in TAMs, and TET3 may be a potential therapeutic target for coordinating ADT.

Unveiling potential: urinary exosomal mRNAs as non-invasive biomarkers for early prostate cancer diagnosis.

BACKGROUND: This study investigated the use of urinary exosomal mRNA as a potential biomarker for the early detection of prostate cancer (PCa). METHODS: Next-generation sequencing was utilized to analyze exosomal RNA from 10 individuals with confirmed PCa and 10 individuals without cancer. Subsequent validation through qRT-PCR in a larger sample of 43 PCa patients and 92 healthy controls revealed distinct mRNA signatures associated with PCa. RESULTS: Notably, mRNAs for RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2 showed promise as diagnostic markers, with AUC values between 0.799 and 0.906 and significance p values. Combining RAB5B and WWP1 in an exoRNA diagnostic model outperformed traditional PSA tests, achieving an AUC of 0.923, 81.4% sensitivity, and 89.1% specificity. CONCLUSIONS: These findings highlight the potential of urinary exosomal mRNA profiling, particularly focusing on RAB5B and WWP1, as a valuable strategy for improving the early detection of PCa.

Identification of tumor immunophenotypes associated with immunotherapy response in bladder cancer.

OBJECTIVES: This study aims to reveal immunophenotypes associated with immunotherapy response in bladder cancer, identify the signature genes of immune subtypes, and provide new molecular targets for improving immunotherapy response. METHODS: Bladder cancer immunophenotypes were characterized in the bulk RNA sequencing dataset GSE32894 and Imvigor210, and gene expression signatures were established to identify the immunophenotypes. Expression of gene signatures were validated in single-cell RNA sequencing dataset GSE145140 and human proteins expression data source. Investigation of Immunotherapy Response was performed in IMvigor210 dataset. Prognosis of tumor immunophenotypes was further analyzed. RESULTS: Inflamed and immune-excluded immunophenotypes were characterized based on the tumor immune cell scores. Risk score models that were established rely on RNA sequencing profiles and overall survival of bladder cancer cohorts. The inflamed tumors had lower risk scores, and the low-risk tumors were more likely to respond to atezolizumab, receiving complete response/partial response (CR/PR). Patients who responded to atezolizumab had higher SRRM4 and lower NPHS1 and TMEM72 expression than the non-responders. SRRM4 expression was a protective factor for bladder cancer prognosis, while the NPHS1 and TMEM72 showed the opposite pattern. CONCLUSION: This study provided a novel classification method for tumor immunophenotypes. Bladder cancer immunophenotypes can predict the response to immune checkpoint blockade. The immunophenotypes can be identified by the expression of signature genes.

Myelin and lymphocyte protein serves as a prognostic biomarker and is closely associated with the tumor microenvironment in the nephroblastoma.

Nephroblastoma, also known as Wilms' tumor (WT), is the most common renal tumor that occurs in children. Although the efficacy of treatment has been significantly improved by a series of comprehensive treatments, some patients still have poor prognosis. Myelin and lymphocyte (MAL) protein, a highly hydrophobic integrated membrane-bound protein, has been implicated in many tumors and is also closely linked to kidney development. However, the relationship between MAL and WT has not yet been elucidated. Therefore, we attempted to evaluate the feasibility of MAL as a promising prognosis factor for WT. The differential expression of MAL was investigated using TARGET database and was verified using the Gene Expression Omnibus database and real-time quantitative PCR. The prognostic ability of MAL was determined using Kaplan-Meier and Cox regression analyses. Pearson correlation analysis was applied to explore the relationship between MAL expression and methylation sites. The ESTIMATE and CIBERSORT algorithms showed that MAL expression was associated with the WT tumor microenvironment. Gene Set Enrichment Analysis (GSEA) indicated that multiple signaling pathways closely associated with tumorigenesis were differentially enriched between the high- and low-MAL groups. In conclusion, our study comprehensively explored the potential of MAL as a prognosis factor for WT. Meanwhile, we also demonstrated that MAL, as a prognostic factor for WT, may be closely related to the tumor microenvironment.

A CD8+ T Cell-Related Genes Expression Signature Predicts Prognosis and the Efficacy of Immunotherapy in Breast Cancer.

Immunotherapy has been applied to patients with breast cancer. However, only part of patients benefits from the current immunotherapy. Accurate prediction of individual response to immunotherapy can be beneficial for breast cancer management. CD8+ T cells are the main force of anti-tumor immunity. This study aimed to establish a CD8+ T cell-related gene expression signature for prediction of breast cancer prognostic and immunotherapy efficacy. RNA-seq transcriptomic data was the basics of this research. Weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis established the prognostic signature. We identified 290 CD8+ T cell-related genes in the training set and established a risk-score model based on 8-genes panel (SOCS1, IL10, CAMK4, CXCL13, KIR2DS4, TESPA1, CD70 and ICAM4). Subsequently, univariate Cox regression analysis suggested that high risk-score was a risk factor for breast cancer (HR = 3.1, 95%CI 2.0-4.8, P < 0.001). In tumor microenvironment, high-risk tumors present decreased tumor infiltrating CD8+ T cells and increased M2 macrophages. The low-risk patients may benefit more from immune checkpoint blockade immunotherapy than the high-risk patients. Moreover, breast tumors which sensitive to immune checkpoint inhibitor (ICI) showed higher IL10 expression.

OGDHL closely associates with tumor microenvironment and can serve as a prognostic biomarker for papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. However, due to the lack of reliable prognostic biomarkers for PTC, overtreatment has been on the rise. Therefore, our research aims to identify new and promising prognostic biomarkers and provide fresh perspectives for clinical decision making. METHODS: The RNA-seq data and clinical data of PTC samples were obtained from The Cancer Genome Atlas data portal. GSE64912 and GSE83520 datasets were downloaded through the GEOquery R package. The difference in the expression of oxoglutarate dehydrogenase like (OGDHL) between PTC and normal tissues was explored by the Wilcoxon test. Kaplan-Meier (KM) and Cox regression analyses were used to further explore the prognostic value of OGDHL. The tumor microenvironments of PTC patients were explored based on ssGSEA and Tumor Immune Estimation Resource online database. Gene Set Enrichment Analysis (GSEA) was performed to explore the biological processes associated with OGDHL. RESULTS: The expression level of OGDHL in PTC was significantly altered compared to that in normal tissues (p < 0.05). Various biological processes associated with OGDHL were also explored through GSEA. KM analysis suggested that the low-OGDHL group had a better overall survival [OS, p = 3.49e-03, hazard ratio (HR) = 4.567]. The receiver operating characteristic curve also indicated the favorable prognostic potential of OGDHL. Moreover, OGDHL was proved to be an independent prognostic indicator in Cox analysis (p = 1.33e-02, HR = 0.152). In the analysis of the tumor microenvironment, the low-OGDHL group showed a lower immune score and stromal score, while tumor purity was higher. The expression of OGDHL was also closely correlated with the infiltration of immune cells. CONCLUSION: Our study elucidated the influence of OGDHL on the prognosis of PTC and demonstrated its potential as a novel biomarker, which would provide new insights into the prognosis monitoring and clinical decision making in PTC patients.

Development of an immune-related gene pairs index for the prognosis analysis of metastatic melanoma.

Melanoma is a skin cancer with great metastatic potential, which is responsible for the major deaths in skin cancer. Although the prognosis of melanoma patients has been improved with the comprehensive treatment, for patients with metastasis, the complexity and heterogeneity of diffuse diseases make prognosis prediction and systematic treatment difficult and ineffective. Therefore, we established a novel personalized immune-related gene pairs index (IRGPI) to predict the prognosis of patients with metastatic melanoma, which was conducive to provide new insights into clinical decision-making and prognostic monitoring for metastatic melanoma. Through complex analysis and filtering, we identified 24 immune-related gene pairs to build the model and obtained the optimal cut-off value from receiver operating characteristic curves, which divided the patients into high and low immune-risk groups. Meantime, the Kaplan-Meier analysis, Cox regression analysis and subgroup analysis showed that IRGPI had excellent prognostic value. Furthermore, IRGPI was shown that was closely associated with immune system in the subsequent tumor microenvironment analysis and gene set enrichment analysis. In addition, we broken through the data processing limitations of traditional researches in different platforms through the application of gene pairs, which would provide great credibility for our model. We believe that our research would provide a new perspective for clinical decision-making and prognostic monitoring in metastatic melanoma.

KRAS expression is a prognostic indicator and associated with immune infiltration in breast cancer.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of death among women. KRAS is known as an oncogene, its expression also associates with cancer prognosis. The purpose of this study was to investigate the prognostic value of KRAS expression in breast cancer and its relationship with immune infiltration. METHODS: Firstly, the expression level and methylation of KRAS were analyzed. Then survival analysis was used to verify the prognostic capability of KRAS expression. After that, gene functional enrichment analysis was performed. The relationship between KRAS gene expression and immune infiltration was researched later. RESULTS: The expression level of KRAS in breast cancer was increased (P = 2.2e-16). Tumor KRAS expression in the subtypes of basal-like, HER2-enriched, Luminal A and Luminal B were 1.64, 1.67, 1.51 and 1.42 times of normal, respectively. 13 methylation sites were different between tumor and normal tissues and associated with KRAS expression. Subsequently, Kaplan-Meier analysis suggested that the high KRAS expression group had a poor prognosis (P = 0.0028). In multivariate Cox regression analysis, KRAS expression was an independent prognostic indicator (HR = 1.353, 95% CI 1.009-1.814, P = 0.044). Gene Ontology (GO) analysis showed enrichment of epidermal growth associated pathways. Additionally, different KRAS expression levels represented different tumor immune infiltration status, which may be caused by the influence of the RAS/MAPK and RAS/PI3K pathways on the level of PD-L1. CONCLUSION: This study suggests that KRAS expression can be used as a prognostic indicator of breast cancer, and it is closely related to tumor immune infiltration.