Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients

Bai, Yi-Yang; Xiao, Wang; Hou, Jie; Geng, Luying; Liang, Xuan; Ruan, Zhiping; Guo, Hui; Kang, Nan; Jiang, Lili

doi:10.3389/fgene.2020.00899

Cited by 8 publications

(4 citation statements)

References 72 publications

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“…A number of studies proposed gene expression-based prognostic models in MPM [3,8,9,[24][25][26][27][28][29][30][31]. They differ significantly in their approaches for feature selection, training and validation datasets, the number of genes included in the final model, as well as in the performance in different MPM cohorts.…”

Section: Discussionmentioning

confidence: 99%

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

2023

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Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. Methods: We developed and validated a two-gene prognostic score (2-PS) using three independent publicly available gene expression datasets. The 2-PS was built using the Robust Likelihood-Based Survival Modeling with Microarray Data method. Results: We narrowed down the model building to the analysis of 179 genes, which have been shown previously to be of importance to MPM development. Our statistical approach showed that a model including two genes (GOLT1B and MAD2L1) was the best predictor for overall survival (OS) (p < 0.0001). The binary score based on the median of the continuous score stratified the patients into low and high score groups and also showed statistical significance in uni- and multivariate models. The 2-PS was validated using two independent transcriptomic datasets. Furthermore, gene set enrichment analysis using training and validation datasets showed that high score patients had distinct gene expression profiles. Our 2-PS also showed a correlation with the estimated infiltration by some immune cell fractions such as CD8+ T cells and M1/2 macrophages. Finally, 2-PS correlated with sensitivity or resistance to some commonly used chemotherapeutic drugs. Conclusion: This is the first study to demonstrate good performance of only two-gene expression-based prognostic scores in MPM. Our initial approach for features selection allowed for an increased likelihood for the predictive value of the developed score, which we were also able to demonstrate.

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Section: Discussionmentioning

confidence: 99%

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

2023

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“…Subsequent and recent works pointed out changes affecting p53/DNA repair and PIK3CA pathways as being associated with reduced overall survival [ 57 , 58 ], demonstrating an overall poorly mutated landscape with high levels of tumor mutational burden (TMB) in only 5% of cases [ 59 ]. Different genetic signatures (including CDH2, CKS2, KIF11, KIF88, Lox, NF2, TP53, SETD2, LATS2, SETDB1, PBRM1, LATS1, SETD5) have been more recently proposed as independent prognostic tools in MPM [ 60 , 61 ]. Very recently, Zhang and coll.…”

Section: Genetic Alterations and Disease Stagementioning

confidence: 99%

The Genes–Stemness–Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints

Stella

Marchiò

Bari

et al. 2023

IJMS

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MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional crosstalk between neoplastic cells and matrix components, among which one main area of focus is hypoxia. Here we discuss the novel therapeutic strategies focused on the exploitation of MPM genetic asset and its interconnection with the surrounding hypoxic microenvironment as well as transcript products and microvesicles representing both an insight into the pathogenesis and promising actionable targets.

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“…The "pheatmap" R package was used to analyze the relationship between the molecular characteristics of MPM patients and other clinical variables in the high-risk and low-risk groups, and the "rms" (19) R package based on the multivariate Cox regression analysis was used to construct the nomogram based on independent prognostic factors, including risk score and M stage. The performance of the nomogram was evaluated by using the ROC curve, and the predictive accuracy of the signature we constructed was evaluated by comparing it with the signature built by previous research (20,21).…”

Section: Validation Of the Independence Of The Prognostic Signature A...mentioning

confidence: 99%

Establishment and validation of a novel immune-related prognostic signature in malignant pleural mesothelioma

Zhang¹,

Huang²,

Wang³

et al. 2022

Ann Transl Med

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Background: Immune-related genes (IRGs) play an important role in the tumor immune microenvironment and affect tumor prognosis. This study aimed to establish a prognostic signature for malignant pleural mesothelioma (MPM) patients. Methods:We obtained the relevant data of MPM patients in The Cancer Genome Atlas (TCGA), and univariate and multivariate Cox regression were used to construct the prediction signature and verify it with the external validation dataset GSE2549. A nomogram was then constructed, and its predictive ability was evaluated and analyzed the level of immune cell infiltration in different groups in the signature.Results: An IRG-related prognostic signature composed of INHBA, CAT, SORT1, TNFSF13B, and BIRC5 was constructed, with patients divided into high-risk and low-risk groups according to the risk score.The survival time of overall survival (OS), progression-free survival (PFS), disease-free interval (DFI), and relapse-free survival (RFS) in low-risk groups was longer than in high-risk groups. Furthermore, the signature had high predictive performance, and the receiver operating characteristic (ROC) of 1, 2, and 3 years could reach 0.853, 0.881, and 0.914, respectively. The predictive accuracy of the signature was verified by using the independent GSE2549 dataset. The levels of activated CD4 T cells, immature dendritic cells, and type 2 T helper cells were higher in high-risk patients. The gene set enrichment analysis (GSEA) analysis showed that a high concentration and P53 signal pathways were found in high-risk groups.Conclusions: This research developed and verified a new type of immune prognostic signature based on five IRGs, which can predict the prognosis of tumor patients and provide new ideas for individualized treatment.

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Identification of a Five-Gene Signature for Predicting Survival in Malignant Pleural Mesothelioma Patients

Cited by 8 publications

References 72 publications

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

The Genes–Stemness–Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints

Establishment and validation of a novel immune-related prognostic signature in malignant pleural mesothelioma

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