Dataset Information

An RNA-binding protein-related risk signature can predict the prognosis and tumor immunity of patients with testicular germ cell tumors.

ABSTRACT:

Background

The functions of RNA-binding proteins (RBPs) in the occurrence and development of tumors remain largely unexplored. We established a risk signature based on RBPs to predict the prognosis, tumor-related immunity, and treatment benefits of patients with testicular germ cell tumors (TGCTs).

Methods

A risk signature was built based on RBPs closely related to survival obtained from TGCT data in The Cancer Genome Atlas (TCGA) database. The ability of the signature to predict prognosis was analyzed by survival curves and Cox regression. The risk signature was validated using the Gene Expression Omnibus (GEO) database. The connection between tumor immunity and the risk score was evaluated. Risk score-related drug sensitivity and biofunctions were also explored.

Results

A risk signature including four selected RBP genes (PARP12, USB1, POLR2E and EED) was established. The prognosis of high-risk TGCT patients was worse than that of low-risk TGCT patients. The risk score was considered a critical factor closely related to prognosis, as determined via Cox regression, and was also closely associated with multiple characteristics of tumor immunity, chemotherapy drugs and biofunctions.

Conclusion

The established risk signature including four selected RBPs in TGCTs could predict the prognosis, tumor-related immunity and treatment benefits of patients with TGCTs. Utilization of this signature could help clinicians make personalized treatment decisions.

SUBMITTER: Fu Y

PROVIDER: S-EPMC9185064 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

An RNA-binding protein-related risk signature can predict the prognosis and tumor immunity of patients with testicular germ cell tumors.

Fu Yang Y Sun Shanshan S Bi Jianbin J Kong Chuize C Shi Du D

American journal of translational research 20220515 5

<h4>Background</h4>The functions of RNA-binding proteins (RBPs) in the occurrence and development of tumors remain largely unexplored. We established a risk signature based on RBPs to predict the prognosis, tumor-related immunity, and treatment benefits of patients with testicular germ cell tumors (TGCTs).<h4>Methods</h4>A risk signature was built based on RBPs closely related to survival obtained from TGCT data in The Cancer Genome Atlas (TCGA) database. The ability of the signature to predict ...[more]

PMID: 35702133

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Project description:BackgroundN6-methyladenosine (m6A) is found to be associated with promoting tumorigenesis in different types of cancers, however, the function of m6A-related genes in testicular germ cell tumors (TGCT) development remains to be illuminated. This study aimed to investigated the prognostic value of m6A RNA methylation regulators in TGCT.MethodsWe collected TGCT patients' information about clinicopathologic parameters and twenty-two m6A regulatory genes expression from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). We analyzed the differentially expressed m6A RNA methylation regulators between tumor tissues and normal tissues, as well as the correlation of m6A RNA methylation regulators. By using Cox univariate analysis, last absolute shrinkage and selection operator (LASSO) Cox regression algorithm and Cox multivariate proportional hazards regression analysis, a risk score was constructed based on a TCGA training cohort, and further verified in the TCGA testing cohort. Then, univariate and multivariate Cox regression analyses were used to evaluate the relationship between risk score and progression-free survival (PFS) in TGCT. Finally, the six-gene risk score was further verified by two gene expression profiles (GSE3218 and GSE10783) as an independent external validation cohort.ResultsDistinct expression patterns of m6A regulatory genes were identified between TGCT tissues and normal tissues in TCGA and GTEx datasets. To predict prognosis of TGCT patients, a risk score was calculated based on six selected m6A RNA methylation regulators (YTHDF1, RBM15, IGF2BP1, ZC3H13, METTL3, and FMR1). Additionally, we found significant differences between the high-risk and low-risk groups in serum marker study levels and histologic subtype. Univariate and multivariate analysis indicated that high risk score was associated with unfavorable PFS. Ultimately, the risk score was further verified by two gene expression profiles (GSE3218 and GSE10783).ConclusionsBased on six selected m6A RNA methylation regulators, we developed a m6A methylation related risk score that can independently predict the prognosis of TGCT patients, and verify the prediction efficiency in TCGA and GEO datasets. Patients in high-risk group were associated with serum tumor marker study levels beyond the normal limits, non-seminoma, and unfavorable survival time. However, further prospective experiments should be carried out to verify our results.

Project description:In recent years, there has been growing evidence linking mitochondrial dysfunction to the development and progression of cancer. However, the role of mitochondrial metabolism-related genes (MMRGs) in testicular germ cell tumor (TGCT) remains unclear. We downloaded clinical pathology, transcriptome, and somatic mutation data for TGCT from public databases and conducted univariate Cox regression analysis to investigate prognostic correlations. We also used consensus clustering to identify molecular subtypes, comparing differential expression genes, biological processes, Kyoto Encyclopedia of Genes and Genomes pathways, mutations, prognosis, immune infiltration, drug sensitivity, and immune therapeutic response between these subtypes. We constructed multi-gene risk features and nomograms for TGCT prognosis. Fifteen MMRGs were significantly correlated with progression-free survival in TGCT patients. Based on these genes, we identified 2 molecular subtypes which showed significant differences in somatic mutations, prognosis, and immune cell infiltration. These subtypes could also indicate drug sensitivity and immune therapeutic response; the subtype with poor prognosis showed a higher potential benefit from some drugs and immunotherapy. Abnormalities in immune-related biological processes and extracellular matrix as well as Kyoto Encyclopedia of Genes and Genomes pathways such as PI3K-AKT signaling pathway, pat5hways in cancer, primary immunodeficiency, and neutrophil extracellular trap formation were associated with significant differences in phenotypes among subtypes. Finally, we constructed an 8-gene TGCT risk feature based on differential expression genes between subtypes which performed well in TGCT patient prognostic evaluation. Our study elucidated the prognostic correlation between MMRGs and TGCT and established MMRG-derived molecular subtypes and risk features for personalized treatment of TGCT which have potential clinical application value.

Project description:Testicular Germ Cell Tumors (TGCTs) are a rare group of neoplasms and the most common solid malignancy arising in young male adults. Despite the good response of these tumors to platinum-based chemotherapy, some patients are refractory to treatment and present poor clinical outcomes. During carcinogenesis and tumor development, cancer cells reprogram energy metabolism toward a hyper-glycolytic phenotype, an emerging hallmark of cancer. This phenomenon, known as the Warburg effect or aerobic glycolysis, involves overexpression of metabolism-related proteins, like glucose and monocarboxylate transporters, pH regulators and intracellular glycolytic enzymes. The metabolic profile of TGCTs is very little explored and, recently, this metabolic rewiring of cancer cells has been associated with aggressive clinicopathological characteristics of these tumors. The overexpression of monocarboxylate transporter 4 (MCT4) in TGCTs has been pointed out as a poor prognostic factor, as well as a promising therapeutic target. As a result, the main aim of the present study was to evaluate the prognostic value of key metabolism-related proteins in TGCTs. The immunohistochemical expressions of CD44 (as a monocarboxylate transporter chaperone), glucose transporter 1 (GLUT1), carbonic anhydrase IX (CAIX), hexokinase II (HKII) and lactate dehydrogenase V (LDHV) were evaluated in a series of 148 adult male patients with TGCTs and associated with clinicopathological parameters. In addition, paired normal tissues were also evaluated. The sample included 75 seminoma and 73 non-seminoma tumors. GLUT1 and CD44 expression was significantly increased in malignant samples when compared to paired normal samples. Conversely, HKII and LDHV expressions were significantly decreased in malignant samples. Concerning the clinicopathological values, CAIX expression was significantly associated with disease recurrence, while HKII expression was significantly associated with aggressive characteristics of TGCTs, including higher staging and non-seminoma histology. In conclusion, this study brings new insights on the metabolic characteristics of TGCTs, showing alterations in the expression of proteins related with the Warburg effect, as well as associations of the hyper-glycolytic and acid-resistant phenotype with aggressive clinicopathological parameters.

Project description:The aim of this study was to build a prognostic model for endometrial cancer (EC) patients based on RNA-binding proteins (RBPs). RNA sequencing and clinical data for uterine corpus EC (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Univariate and multivariate Cox regression analysis were used to obtain the following risk formula: score = sum (corresponding coefficient × expression of each gene). A nomogram was developed to accurately predict patient survival based on risk score, age, stage, and grade. Immunohistochemistry (IHC) was used to verify the expression of RBPs in EC. The mRNA expression of RBPs was measured by qRT-PCR. The effects of RBPs on the malignant biologic behavior of EC were detected using CCK-8, colony formation, and transwell invasion assays. A novel prognostic signature was constructed, comprising three RBPs (CD3EAP, SBDS, and TDRKH). The risk score was: Risk score = (0.860 × CD3EAP expression) + (0.622 × 6SBDS expression) + (0.427 × 4TDRKH expression). The area under the receiver operating characteristic curves (AUCs) of risk score for 1-, 3-, and 5-year overall survival (OS) was 0.75, 0.68, and 0.65, respectively. The AUCs of the nomogram for 1-, 3-, and 5-year OS were 0.811, 0.793, and 0.814, respectively. In our independent cohort, the IHC results revealed that CD3EAP (P < 0.001) and TDRKH (P < 0.001) were upregulated and SBDS (P < 0.001) was downregulated in EC. Immunostaining showed the expression levels of CD3EAP, SBDS and TDRKH for each patient and these were multiplied by their respective coefficients of 0.860, 0.622 and 0.427 to obtain the risk scores. The AUCs of risk score for 1-, 3-, and 5-year OS were 0.888, 0.793, and 0.780 respectively. The AUCs of the nomogram for 1-, 3-, and 5-year OS were 0.790, 0.826, and 0.906, respectively. Cell functional experiments also confirmed the influence of the key RBPs on the malignant biologic behavior of EC. In summary, a characteristic model based on our three RBPs accurately predicted the prognosis of EC. Our in-depth analysis of these RBPs may inform the development of novel strategies for the diagnosis and treatment of EC.

Dataset Information

An RNA-binding protein-related risk signature can predict the prognosis and tumor immunity of patients with testicular germ cell tumors.

Background

Methods

Results

Conclusion

Publications

An RNA-binding protein-related risk signature can predict the prognosis and tumor immunity of patients with testicular germ cell tumors.

Similar Datasets

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