Background: B cells are essential components of tumor microenvironment and exert important functions in anti-tumor immune response. However, the prognosis value of B cell-related genes in bladder cancer (BLCA) remains obscure. Materials and Methods: The infiltrating levels of B cells were measured via the CD20 staining in the local samples and the computational biology analyses in the TCGA-BLCA cohort. The single-cell RNA sequencing analysis, gene-pair strategy, LASSO regression, random forest, and Cox regression were used for B cell-related signature construction. TCGA-BLCA cohort was chosen as the training cohort, and three independent cohorts from GEO and the local cohort were used for external validation. 326 B cells were adopted to explore the association between the model and B cells' biological processes. TIDE algorithm and two BLCA cohorts receiving anti-PD1/PDL1 treatment were utilized to detect its predictive ability to the immunotherapeutic response. Results: High infiltration levels of B cells heralded favorable prognosis, both in the TCGA-BLCA cohort and the local cohort (all P < 0.05). A 5-gene-pair model was established and served as a significant prognosis predictor across multiple cohorts (pooled hazard ratio = 2.79, 95% confidence interval = 2.22-3.49). The model could evaluate the prognosis effectively in 21 of 33 cancer types (P < 0.05). The signature was negatively associated with B cells' activation, proliferation, and infiltrating levels, and could serve as a potential predictor of immunotherapeutic outcomes. Conclusions: A B cell-related gene signature was constructed to predict the prognosis and immunotherapeutic sensitivity in BLCA, helping to guide the personalized treatment.
As a special pattern of programmed cell death, ferroptosis is reported to participate in several processes of tumor progression, including regulating proliferation, suppressing apoptotic pathways, increasing metastasis, and acquiring drug resistance. The marked features of ferroptosis are an abnormal intracellular iron metabolism and lipid peroxidation that are pluralistically modulated by ferroptosis-related molecules and signals, such as iron metabolism, lipid peroxidation, system Xc−, GPX4, ROS production, and Nrf2 signals. Non-coding RNAs (ncRNAs) are a type of functional RNA molecules that are not translated into a protein. Increasing studies demonstrate that ncRNAs have a diversity of regulatory roles in ferroptosis, thus influencing the progression of cancers. In this study, we review the fundamental mechanisms and regulation network of ncRNAs on ferroptosis in various tumors, aiming to provide a systematic understanding of recently emerging non-coding RNAs and ferroptosis.
Background As an indispensable component of the inflammasome, absent in melanoma 2 (AIM2) plays an essential role in the initiation of the innate immune response, while its effects on clear cell renal cell carcinoma (ccRCC) still remain unclear. In this research, we aimed to evaluate the predictive value of AIM2 on prognosis and immunotherapy effects in patients suffering from ccRCC. Methods In this study, genomic and phenotypic data obtained from public databases and ccRCC patient samples from NanFang hospital were collected for exploring the correlation between AIM2 and ccRCC progression. Then we also investigated the association between AIM2 and tumor immune microenvironment of ccRCC patients. Finally, the efficacy of AIM2 was tested to predict the response to immunotherapy of ccRCC patients. Results Our study verified that AIM2 was significantly overexpressed in ccRCC tissues compared to adjacent normal tissues with the potential contributing factors including low methylation level and high copy number amplification level of AIM2. AIM2 was an independent prognostic marker of ccRCC patients and significantly associated with higher malignancy. Further analysis suggested that AIM2 was implicated in tumor immune microenvironment (TIME), showing a closely positive association with most inhibitory immune checkpoints. Thus, we further elucidated that ccRCC patients with higher AIM2 mRNA expression levels had more sensitive immunotherapy responses. Conclusions This research determined the predictive value of AIM2 in predicting the prognostic and immunotherapy effects of ccRCC patients and revealed its potential to efficiently pick out certain patients that may benefit from cancer immunotherapy.
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