A somatic mutation-derived LncRNA signatures of genomic instability predicts the prognosis and tumor microenvironment immune characters in hepatocellular carcinoma

Jin, Chuan; Zhao, Jian-Sen; Huang, Xu-Qi; Yang, Xian-Zi; Niu, Fei-Yu; Lin, Jinrong; Ma, Lei; Shi, Yanxia; Li, Xiaoshan; Jiang, Peng; Gao, Sha; Li, Feng; Song, Ye

doi:10.1007/s12072-022-10375-y

Cited by 6 publications

(3 citation statements)

References 51 publications

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“…In a previous study, a risk score for disul dptosisrelated genes was established to predict prognosis and guide clinical treatment [19]. Although there are many studies on the use of lncRNAs as molecular biomarkers to predict the prognosis of HCC patients, no study has systematically used DRLs as molecular biomarkers to predict the prognosis of HCC patients [20][21][22][23]. To our knowledge, this is the rst study of the prognostic signature of DRLs to predict prognosis in patients with HCC.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a prognostic signature for hepatocellular carcinoma using disulfidptosis-related lncRNAs

Yang,

Zhou,

et al. 2023

Preprint

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Background Disulfidptosis is a recently discovered form of programmed cell death that may be a new direction in tumor treatment. Long non-coding RNAs (lncRNAs) play an important role in the development and progression of hepatocellular carcinoma (HCC). However, how disulfidptosis-related lncRNAs (DRLs) are involved in regulating HCC is not yet understood. This study aimed to establish a prognostic signature for DRLs and analyze their clinical value in patients with HCC. Method RNA sequencing, mutation, and clinically relevant data were collected from the Cancer Genome Atlas database (TCGA). Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox analysis were conducted to evaluate DRLs. On the basis of these analyses, a prognostic signature was developed. Subsequently, we validated the accuracy of this prognostic signature using receiver operating characteristic (ROC) curves, C-index, survival curve, nomogram, and principal component analysis (PCA). Finally, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, gene set enrichment analysis (GSEA), tumor mutation burden (TMB) analysis, immune-related analysis, tumor immune dysfunction and exclusion (TIDE) analysis, and half-maximal inhibitory concentration (IC50) predictions. Results A prognostic signature consisting of MKLN1-AS, TMCC1-AS1, AL603839.2, AC245060.7 and AL049840.3 was developed. This prognostic signature demonstrated reliable predictive capability for estimating the survival time of patients with HCC. We observed notable differences between the high- and low-risk groups in terms of immune cell population, immune function, TIDE, and IC50. Conclusions A new prognostic signature was developed based on the five DRLs to predict the prognosis of patients with HCC, which may be helpful for individualized therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Establishment of a prognostic signature for hepatocellular carcinoma using disulfidptosis-related lncRNAs

Yang,

Zhou,

et al. 2023

Preprint

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“…From an omics and bioinformatics point of view, we can broadly classify the approaches that have been developed to prioritize lncRNAs with a possible association with cancer into at least two categories: (1) an early integrative analysis of somatic variants with cancer driver potential that have an impact on the functional activity of lncRNAs associated with prognosis in cancer patients [37,38,[69][70][71], and (2) post-analysis integration strategies centered on the relationship between genome instability and lncRNAs with aberrant expressions associated with tumor prognosis [39][40][41][42][43][44][45] (Figure 2). A representative study was conducted to evaluate the potential impact of somatic mutations in human lncRNAs (denominated MutLncs) and their functional significance in cancer, interrogate the mutation profiles in genomic regions harboring lncRNA and their vicinity across 17 cancer types, and use an integrative pipeline to describe the significance of the MutLncs contribution to cancer [69].…”

Section: Approaches For Prioritizing Cancer Driver Lncrnas Using Soma...mentioning

confidence: 99%

Multi-Omics Mining of lncRNAs with Biological and Clinical Relevance in Cancer

Salido-Guadarrama,

Romero-Cordoba,

Rueda-Zarazua

2023

IJMS

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In this review, we provide a general overview of the current panorama of mining strategies for multi-omics data to investigate lncRNAs with an actual or potential role as biological markers in cancer. Several multi-omics studies focusing on lncRNAs have been performed in the past with varying scopes. Nevertheless, many questions remain regarding the pragmatic application of different molecular technologies and bioinformatics algorithms for mining multi-omics data. Here, we attempt to address some of the less discussed aspects of the practical applications using different study designs for incorporating bioinformatics and statistical analyses of multi-omics data. Finally, we discuss the potential improvements and new paradigms aimed at unraveling the role and utility of lncRNAs in cancer and their potential use as molecular markers for cancer diagnosis and outcome prediction.

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“…Somatic mutations are also predictive factors for immunotherapy, and in addition to TMB, somatic mutations are considered predictive biomarkers for high-grade solid tumors. 8 It has been reported that The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) have provided a detailed description of the genetic landscape associated with PAAD. Our study uses TCGA and ICGC data to describe the somatic mutation characteristics of PAAD patients.…”

Section: Introductionmentioning

confidence: 99%

Mutations in lysine methyltransferase 2C and PEG3 are associated with tumor mutation burden, prognosis, and antitumor immunity in pancreatic adenocarcinoma patients

2022

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Background As a common cancer-related death worldwide, pancreatic adenocarcinoma (PAAD) has significantly increased mortality in recent years. In recent years, tumor mutation burden (TMB) has been regarded as the most popular biomarker for PAAD immunotherapy. However, it remains unclear which gene mutations affect TMB and immune response in pancreatic adenocarcinoma. Methods The somatic mutation images of PAAD samples were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Based on the expression data of the TCGA and IGCC cohorts, various bioinformatics algorithms are used for evaluating the prognostic value and functional annotation of some frequently somatically mutated genes. Furthermore, the correlation between gene mutation and tumor immunity was also evaluated. Results The results showed that lysine methyltransferase 2C (KMT2C) and paternally expressed 3 (PEG3) are frequently mutated genes in PAAD. Patients with KMT2C and PEG3 mutations have higher TMB severity and a lousy prognosis. In addition, the mutations of KMT2C and PEG3 genes positively regulate the metabolic and protein-related pathways in PAAD. Meanwhile, significant differences in the composition of the immune cells were observed for KMT2C and PEG3 mutations PAAD patients, for providing additional guidelines for antitumor treatments in various KMT2C and PEG3 mutation states in PAAD. Conclusion This study reveals that KMT2C and PEG3 mutation may serve as biomarkers for predicting prognosis and guiding anti-PAAD immunotherapy for PAAD patients.

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A somatic mutation-derived LncRNA signatures of genomic instability predicts the prognosis and tumor microenvironment immune characters in hepatocellular carcinoma

Cited by 6 publications

References 51 publications

Establishment of a prognostic signature for hepatocellular carcinoma using disulfidptosis-related lncRNAs

Establishment of a prognostic signature for hepatocellular carcinoma using disulfidptosis-related lncRNAs

Multi-Omics Mining of lncRNAs with Biological and Clinical Relevance in Cancer

Mutations in lysine methyltransferase 2C and PEG3 are associated with tumor mutation burden, prognosis, and antitumor immunity in pancreatic adenocarcinoma patients

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