Dataset Information

DNA Repair Genes Are Associated with Subtype Classification, Prognosis, and Immune Infiltration in Uveal Melanoma.

ABSTRACT: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. DNA repair genes play a vital role in cancer development. However, there has been very little research about DNA repair genes in UM. This study aimed to evaluate the importance of DNA repair genes and established a signature for predicting prognosis and immune features of UM. In this study, we mined TCGA database through bioinformatics analysis, and the intersect was taken between DNA repair genes and prognosis related genes and yielded 52 genes. We divided 80 UM patients into C1 and C2 subtypes. GSEA results indicated that abundant cancer-promoting functions and signaling pathways were activated in C2 subtype and the proportion of SNVs was higher in C2 than in C1 which suggested a worse prognosis. We built a six DNA repair genes model including ITPA, CETN2, CCNO, POLR2J, POLD1, and POLA1 by LASSO regression to predict prognosis of UM patients and utilized the median value of risk scores as the cutoff point to differentiate high risk and low risk group. The survival analyses and the receiver operating characteristic (ROC) curves in the validation group and entire data set confirmed the accuracy of this model. We also constructed a nomogram based on age and risk scores to evaluate the relationship between risk scores and clinical outcome. The calibration curve of the overall survival (OS) indicated that the performance of this model is steady and robust. Finally, the enrichment analysis showed that there were complex regulatory mechanisms in UM patients. The immune infiltration analysis indicated that the immune infiltration in C2 in the high risk group was different from that in the low risk group. Our findings indicated that the DNA repair genes may be related to UM prognosis and provide new insight into the underlying mechanisms.

SUBMITTER: Wang T

PROVIDER: S-EPMC8791741 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundIn uveal melanomas, immune infiltration is a marker of poor prognosis. This work intended to decipher the biological characteristics of intra-tumor immune population, compare it to other established biomarkers and to patients' outcome.MethodsPrimary, untreated, and mainly large uveal melanomas with retinal detachment were analyzed using: transcriptomic profiling (n = 15), RT-qPCR (n = 36), immunohistochemistry (n = 89), Multiplex Ligation-dependent Probe Amplification (MLPA) for copy number alterations (CNA) analysis (n = 89), array-CGH (n = 17), and survival statistics (n = 86).ResultsGene expression analysis divided uveal melanomas into two groups, according to the IFNγ/STAT1-IRF1 pathway activation. Tumors with IFNγ-signature had poorer prognosis and showed increased infiltration of CD8+ T lymphocytes and macrophages. Cox multivariate analyses of immune cell infiltration with MLPA data delineated better prognostic value for three prognostic groups (three-tier stratification) than two (two-tier stratification). CNA-based model comprising monosomy 3, 8q amplification, and LZTS1and NBL1 deletions emerged as the best predictor for disease-free survival. It outperformed immune cell infiltration in receiver operating characteristic curves. The model that combined CNA and immune infiltration defined risk-groups according to the number of DNA alterations. Immune cell infiltration was increased in the high-risk group (73.7%), where it did not correlate with patient survival, while it was associated with poorer outcome in the intermediate risk-group.ConclusionsHigh degree of immune cell infiltration occurs in a subset of uveal melanomas, is interferon-gamma-related, and associated with poor survival. It allows for two-tier stratification, which is prognostically less efficient than a three-tier one. The best prognostic stratification is by CNA model with three risk-groups where immune cell infiltration impacts only some subgroups.

Project description:Skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) is the most lethal skin cancer with increasing incidence. Regulated cell death plays an important role in tumorigenesis and serves as an important target for almost all treatment strategies. Cuproptosis is the most recently identified copper-dependent regulated cell death form that relies on mitochondria respiration. However, its role in tumorigenesis remains unknown. The correlation of cuproptosis-related genes with tumor prognosis is far to be understood, either. In the present study, we explored the correlation between cuproptosis-related genes with the prognosis of melanoma by accessing and analyzing a public database and found 11 out 12 genes were upregulated in melanoma tissues and three genes (LIPT1, PDHA1, and SLC31A1) have predictive value for the prognosis. The subgroup of melanoma patients with higher cuproptosis-related gene expression showed longer overall survival than those with lower gene expression. We chose LIPT1 for further exploration. LIPT1 expression was increased in melanoma biopsies and was an independent favorable prognostic indicator for melanoma patients. Moreover, LIPT1 expression was positively correlated with PD-L1 expression and negatively associated with Treg cell infiltration. The melanoma patients with higher LIPT1 expression showed longer overall survival than those with lower LIPT1 expression after receiving immunotherapy, indicating the prognostic predictive value of LIPT1. Finally, a pan-cancer analysis indicated that LIPT1 was differentially expressed in diverse cancers as compared to normal tissues and correlated with the expression of multiple immune checkpoints, especially PD-L1. It could serve as a favorable prognosis indicator in some cancer types. In conclusion, our study demonstrated the prognostic value of cuproptosis-related genes, especially LIPT1, in melanoma, and revealed the correlation between LIPT1 expression and immune infiltration in melanoma, thus providing new clues on the prognostic assessment of melanoma patients and providing a new target for the immunotherapy of melanoma.

Project description:Background: As a recurrent inflammatory bone disease, the treatment of osteomyelitis is always a tricky problem in orthopaedics. N6-methyladenosine (m6A) regulators play significant roles in immune and inflammatory responses. Nevertheless, the function of m6A modification in osteomyelitis remains unclear. Methods: Based on the key m6A regulators selected by the GSE16129 dataset, a nomogram model was established to predict the incidence of osteomyelitis by using the random forest (RF) method. Through unsupervised clustering, osteomyelitis patients were divided into two m6A subtypes, and the immune infiltration of these subtypes was further evaluated. Validating the accuracy of the diagnostic model for osteomyelitis and the consistency of clustering based on the GSE30119 dataset. Results: 3 writers of Methyltransferase-like 3 (METTL3), RNA-binding motif protein 15B (RBM15B) and Casitas B-lineage proto-oncogene like 1 (CBLL1) and three readers of YT521-B homology domain-containing protein 1 (YTHDC1), YT521-B homology domain-containing family 3 (YTHDF2) and Leucine-rich PPR motif-containing protein (LRPPRC) were identified by difference analysis, and their Mean Decrease Gini (MDG) scores were all greater than 10. Based on these 6 significant m6A regulators, a nomogram model was developed to predict the incidence of osteomyelitis, and the fitting curve indicated a high degree of fit in both the test and validation groups. Two m6A subtypes (cluster A and cluster B) were identified by the unsupervised clustering method, and there were significant differences in m6A scores and the abundance of immune infiltration between the two m6A subtypes. Among them, two m6A regulators (METTL3 and LRPPRC) were closely related to immune infiltration in patients with osteomyelitis. Conclusion: m6A regulators play key roles in the molecular subtypes and immune response of osteomyelitis, which may provide assistance for personalized immunotherapy in patients with osteomyelitis.

Dataset Information

DNA Repair Genes Are Associated with Subtype Classification, Prognosis, and Immune Infiltration in Uveal Melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets