Identifying enhancer-driven subtype-specific prognostic markers in breast cancer based on multi-omics data

Zhao, Hongying; Zhang, Siwen; Yin, Xiangzhe; Zhang, Caiyu; Wang, Lixia; Liu, Kailai; Xu, Haotian; Liu, Wangyang; Bo, Lin; Lin, Shan; Feng, Ke; Lin, Lin; Fei, Meiting; Ning, Shangwei; Wang, Li

doi:10.3389/fimmu.2022.990143

Cited by 2 publications

(1 citation statement)

References 54 publications

(39 reference statements)

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“…Ornithine decarboxylase antizyme ( OAZ1 gene) is a potential therapeutic target in various malignant tumors because it plays relevant roles in cellular functions, including genomic stability, proliferation, differentiation, and apoptosis [ 42 ]. The enhancer-related lncRNA-mRNA pairs as prognostic biomarkers AC0-27307.2- OAZ1 in the Basal-like subtype of breast cancer [ 43 ] and as a fusion gene. The up-regulation of the OAZ1 gene has been demonstrated in three studies in oral squamous cell carcinoma (OSCC) [ 44 ] and chronic myeloid leukemia (CML) [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

Salgado,

Prado Montes de Oca,

Chairez

et al. 2024

Biomedicines

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The molecular explanation about why some pancreatic cancer (PaCa) patients die early and others die later is poorly understood. This study aimed to discover potential novel markers and drug targets that could be useful to stratify and extend expected survival in prospective early-death patients. We deployed a deep learning algorithm and analyzed the gene copy number, gene expression, and protein expression data of death versus alive PaCa patients from the GDC cohort. The genes with higher relative amplification (copy number >4 times in the dead compared with the alive group) were EWSR1, FLT3, GPC3, HIF1A, HLF, and MEN1. The most highly up-regulated genes (>8.5-fold change) in the death group were RPL30, RPL37, RPS28P7, RPS11, Metazoa_SRP, CAPNS1, FN1, H3−3B, LCN2, and OAZ1. None of their corresponding proteins were up or down-regulated in the death group. The mRNA of the RPS28P7 pseudogene could act as ceRNA sponging the miRNA that was originally directed to the parental gene RPS28. We propose RPS28P7 mRNA as the most druggable target that can be modulated with small molecules or the RNA technology approach. These markers could be added as criteria to patient stratification in future PaCa drug trials, but further validation in the target populations is encouraged.

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Section: Discussionmentioning

confidence: 99%

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

Salgado,

Prado Montes de Oca,

Chairez

et al. 2024

Biomedicines

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Ferroptosis-related lncRNAs guiding osteosarcoma prognosis and immune microenvironment

Yang,

Su,

et al. 2023

J Orthop Surg Res

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Objective To investigate the ferroptosis-related long non-coding RNAs (FRLncs) implicated in influencing the prognostic and immune microenvironment in osteosarcoma (OS), and to establish a foundational framework for informing clinical decision making pertaining to OS management. Methods Transcriptome data and clinical data pertaining to 86 cases of OS, the GSE19276, GSE16088 and GSE33382 datasets, and a list of ferroptosis-related genes (FRGs) were used to establish a risk prognostic model through comprehensive analysis. The identification of OS-related differentially expressed FRGs was achieved through an integrated analysis encompassing the aforementioned 86 OS transcriptome data and the GSE19276, GSE16088 and GSE33382 datasets. Concurrently, OS-related FRLncs were ascertained via co-expression analysis. To establish a risk prognostic model for OS, Univariate Cox regression analysis and Lasso Cox regression analysis were employed. Subsequently, a comprehensive evaluation was conducted, comprising risk curve analysis, survival analysis, receiver operating characteristic curve analysis and independent prognosis analysis. Model validation with distinct clinical subgroups was performed to assess the applicability of the risk prognostic model to diverse patient categories. Moreover, single sample gene set enrichment analysis (ssGSEA) was conducted to investigate variations in immune cell populations and immune functions within the context of the risk prognostic model. Furthermore, an analysis of immune checkpoint differentials yielded insights into immune checkpoint-related genes linked to OS prognosis. Finally, the risk prognosis model was verified by dividing the samples into train group and test group. Results We identified a set of seven FRLncs that exhibit potential as prognostic markers and influence factors of the immune microenvironment in the context of OS. This ensemble encompasses three high-risk FRLncs, denoted as APTR, AC105914.2 and AL139246.5, alongside four low-risk FRLncs, designated as DSCR8, LOH12CR2, AC027307.2 and AC025048.2. Furthermore, our analysis revealed notable down-regulation in the high-risk group across four distinct immune cell types, namely neutrophils, natural killer cells, plasmacytoid dendritic cells and tumor-infiltrating lymphocytes. This down-regulation was also reflected in four key immune functions, antigen-presenting cell (APC)-co-stimulation, checkpoint, cytolytic activity and T cell co-inhibition. Additionally, we identified seven immune checkpoint-associated genes with significant implications for OS prognosis, including CD200R1, HAVCR2, LGALS9, CD27, LAIR1, LAG3 and TNFSF4. Conclusion The findings of this study have identified FRLncs capable of influencing OS prognosis and immune microenvironment, as well as immune checkpoint-related genes that are linked to OS prognosis. These discoveries establish a substantive foundation for further investigations into OS survival and offer valuable insights for informing clinical decision making in this context.

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Identifying enhancer-driven subtype-specific prognostic markers in breast cancer based on multi-omics data

Cited by 2 publications

References 54 publications

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

Deep Learning Techniques to Characterize the RPS28P7 Pseudogene and the Metazoa-SRP Gene as Drug Potential Targets in Pancreatic Cancer Patients

Ferroptosis-related lncRNAs guiding osteosarcoma prognosis and immune microenvironment

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