Abstract
Background While N6-methyladenosine (m6A) modification of RNA and the tumor immune microenvironment both influence the progression of cancer, little attention has been paid to interactions between these two factors. Thus, we systematically explored potential biomarkers in the malignant progression of bladder urothelial carcinoma (BLCA) via combining expression of m6A methylation regulators with tumor immune infiltration. Methods We extracted m6A regulators from published literature, downloaded BLCA RNA-seq and clinical information from the Cancer Genome Atlas database, and integrated three main bioinformatic methods and qPCR to explore the biological variations in the malignant progression of BLCA. Results FTO, IGF2BP3, and YTHDC1 have a significant difference in bladder cancer and prognosis. Two subgroups (clusters 1 and 2) were identified according to three key m6A regulators; cluster 1 was preferentially associated with poor prognosis and immune infiltration relative to cluster 2 significantly. We further identified PGM1 and ENO1 as potential prognostic biomarkers, as they were correlated with FTO and IGF2BP3 positively but with YTHDC1, negatively. M2 macrophage and TFH cells were highly infiltrated in BLCA and were associated with BLCA prognosis. Finally, PGM1 and ENO1 were correlated with M2 macrophage and TFH cells and their surface markers CD163and CXCR5. Conclusions PGM1 and ENO1 are highly correlated with the malignant progression of BLCA, and the expression of these genes may be new indicators for the diagnosis and prognosis of BLCA.
Highlights
Bladder urothelial carcinoma (BLCA) is a type of therioma that has high rates of morbidity and mortality
Yi et al [10] found that the imbalance of the immune system plays a crucial role in the progress of head and neck squamous cell carcinomas and that many cytokines and immunosuppressive cells in the microenvironment of these tumors facilitate immune escape. erefore, understanding immune infiltration in the tumor microenvironment (TME) is likely significant to improving response rates and developing new immunotherapy strategies
We investigated the expression of PGM1, ENO1, and m6A-related genes to identify the potential mechanism of aberrant upregulation in bladder urothelial carcinoma (BLCA). e correlation analysis exhibited that the expression of PGM1, ENO1, and m6Arelated genes was highly correlated (see Figures 4(c) and 4(d))
Summary
Bladder urothelial carcinoma (BLCA) is a type of therioma that has high rates of morbidity and mortality. Studies have shown that cells of the adaptive and innate immune systems infiltrate into the TME and regulate tumor progression [9]. Erefore, understanding immune infiltration in the TME is likely significant to improving response rates and developing new immunotherapy strategies. Us, we systematically explored potential biomarkers in the malignant progression of bladder urothelial carcinoma (BLCA) via combining expression of m6A methylation regulators with tumor immune infiltration. We extracted m6A regulators from published literature, downloaded BLCA RNA-seq and clinical information from the Cancer Genome Atlas database, and integrated three main bioinformatic methods and qPCR to explore the biological variations in the malignant progression of BLCA. PGM1 and ENO1 are highly correlated with the malignant progression of BLCA, and the expression of these genes may be new indicators for the diagnosis and prognosis of BLCA
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