A RNA sequencing-based six-gene signature for survival prediction in patients with glioblastoma

Zuo, Shuguang; Zhang, Xinhong; Wang, Liping

doi:10.1038/s41598-019-39273-4

Cited by 50 publications

(52 citation statements)

References 51 publications

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“…There has been significant progress in understanding genomic drivers implicated in glioma tumorigenesis. Multidimensional data from genomics studies such as The Cancer Genome Atlas (TCGA) 46 , REMBRANDT study 47 , and the Chinese Glioma Genome Atlas (CGGA) 48 have identified molecular signatures associated with glioma subtypes and their prognoses 49 . Isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion are most prominent markers associated with a more favourable prognosis 49 .…”

Section: Discussionmentioning

confidence: 99%

Longer-term (≥ 2 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: a systematic review and meta-analysis

Poon

Sudlow

Figueroa

et al. 2020

Sci Rep

196

128

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Translation of survival benefits observed in glioblastoma clinical trials to populations and to longerterm survival remains uncertain. We aimed to assess if ≥ 2-year survival has changed in relation to the trial of radiotherapy plus concomitant and adjuvant temozolomide published in 2005. We searched MEDLINE and Embase for population-based studies with ≥ 50 patients published after 2002 reporting survival at ≥ 2 years following glioblastoma diagnosis. Primary endpoints were survival at 2-, 3-and 5-years stratified by recruitment period. We meta-analysed survival estimates using a random effects model stratified according to whether recruitment ended before 2005 (earlier) or started during or after 2005 (later). PROSPERO registration number CRD42019130035. Twentythree populations from 63 potentially eligible studies contributed to the meta-analyses. Pooled 2-year overall survival estimates for the earlier and later study periods were 9% (95% confidence interval [CI] 6-12%; n/N = 1,488/17,507) and 18% (95% CI 14-22%; n/N = 5,670/32,390), respectively. Similarly, pooled 3-year survival estimates increased from 4% (95% CI 2-6%; n/N = 325/10,556) to 11% (95% CI 9-14%; n/N = 1900/16,397). One study with a within-population comparison showed similar improvement in survival among the older population. Pooled 5-year survival estimates were 3% (95% CI 1-5%; n/N = 401/14,919) and 4% (95% CI 2-5%; n/N = 1,291/28,748) for the earlier and later periods, respectively. Meta-analyses of real-world data suggested a doubling of 2-and 3-year survival in glioblastoma patients since 2005. However, 5-year survival remains poor with no apparent improvement. Detailed clinically annotated population-based data and further molecular characterization of longer-term survivors may explain the unchanged survival beyond 5 years. Glioblastoma multiforme is the most common primary malignant brain tumour in adults with an incidence rate of 3.7 per 100,000 person-years, though geographical variation exists 1. Despite an increasing understanding of the underlying pathophysiology, glioblastoma remains an incurable disease with high mortality 2. A landmark clinical trial in 2005 demonstrated that the addition of concomitant and adjuvant temozolomide to radiotherapy provided an additional survival benefit to patients diagnosed with glioblastoma 3. Multiple clinical trials had investigated novel therapies that showed promise in pre-clinical and early phase studies, but to date there have been no major additions to the treatment armamentarium for newly diagnosed patients since 2005. The median survival in the intervention arm of the 2005 trial was 14.6 months 3 , but there is uncertainty about whether survival benefit from clinical trials is translated to the population 4,5. Clinical trial participation itself is associated with better survival 6 , which may be caused by the preferential inclusion and exclusion criteria into clinical trials. In clinical practice not all patients are eligible for the trial standard of care involving maximal surgical debul...

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Section: Discussionmentioning

confidence: 99%

Longer-term (≥ 2 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: a systematic review and meta-analysis

Poon

Sudlow

Figueroa

et al. 2020

Sci Rep

196

128

View full text Add to dashboard Cite

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“…And the combination of multiple prognostic genes seems to be more valuable and promising. Prognostic prediction models based on multiple genes combination have been established and validated in many cancers [7,16,17].…”

Section: Discussionmentioning

confidence: 99%

Identification of a four-gene panel predicting overall survival for lung adenocarcinoma

Chunyu

Qizhong

Danni

et al. 2020

Preprint

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Abstract Background: Lung cancer is the most frequently diagnosed carcinoma and the leading cause of cancer-related mortality. Although molecular targeted therapy and immunotherapy have made great progress, the overall survival (OS) is still poor due to a lack of accurate and available prognostic biomarkers. Therefore, in this study we aimed to establish a multiple-gene panel predicting OS for lung adenocarcinoma.Methods: We obtained the mRNA expression and clinical data of lung adenocarcinoma (LUAD) from TCGA database for further integrated bioinformatic analysis. Lasso regression and Cox regression were performed to establish a prognosis model based on a multi-gene panel. Nomogram was built based on the model. The receiver operating characteristic (ROC) curve and the Kaplan–Meier curve were used to assess the predicted capacity of the model. The prognosis value of the multi-gene panel was further validated in TCGA-LUAD patients with EGFR, KRAS and TP53 mutation and a dataset from GEO. Gene set enrichment analysis (GSEA) was performed to explore potential biological mechanisms of a novel prognostic gene signature.Results: A four-gene panel (including DKK1, GNG7, LDHA, MELTF) was established as a prognostic indicator for OS of LUAD. The ROC curve revealed good predicted performance in both test cohort (AUC = 0.740) and validation cohort (AUC = 0.752). Each patient was calculated a risk score according to the model based on the four-gene panel. The results showed that the risk score was an independent prognostic factor, and the high-risk group had a worse OS compared with the low-risk group. The nomogram based on this model shows better prediction performance. The four-gene panel was still good predictors for OS in LUAD patients with EGFR, KRAS and TP53 mutations. The four genes may be significantly related to the metabolism of genetic material, especially in the regulation of cell cycle pathway.Conclusion: Our study proposed a novel four-gene panel to predict the OS of LUAD, which may contribute to predicting prognosis accurately and making the clinical decisions of individual therapy for LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Identification of a four‑gene panel predicting overall survival for lung adenocarcinoma

Qizhong

Danni

et al. 2020

Preprint

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Background: Lung cancer is the most frequently diagnosed carcinoma and the leading cause of cancer-related mortality. Although molecular targeted therapy and immunotherapy have made great progress, the overall survival (OS) is still poor due to a lack of accurate and available prognostic biomarkers. Therefore, in this study we aimed to establish a multiple-gene panel predicting OS for lung adenocarcinoma.Methods: We obtained the mRNA expression and clinical data of lung adenocarcinoma (LUAD) from TCGA database for further integrated bioinformatic analysis. Lasso regression and Cox regression were performed to establish a prognosis model based on a multi-gene panel. A nomogram based on this model was constructed. The receiver operating characteristic (ROC) curve and the Kaplan–Meier curve were used to assess the predicted capacity of the model. The prognosis value of the multi-gene panel was further validated in TCGA-LUAD patients with EGFR, KRAS and TP53 mutation and a dataset from GEO. Gene set enrichment analysis (GSEA) was performed to explore potential biological mechanisms of a novel prognostic gene signature.Results: A four-gene panel (including DKK1, GNG7, LDHA, MELTF) was established for LUAD prognostic indicator. The ROC curve revealed good predicted performance in both test cohort (AUC = 0.740) and validation cohort (AUC = 0.752). Each patient was calculated a risk score according to the model based on the four-gene panel. The results showed that the risk score was an independent prognostic factor, and the high-risk group had a worse OS compared with the low-risk group. The nomogram based on this model showed good prediction performance. The four-gene panel was still good predictors for OS in LUAD patients with TP53 and KRAS mutations. GSEA revealed that the four genes may be significantly related to the metabolism of genetic material, especially the regulation of cell cycle pathway.Conclusion: Our study proposed a novel four-gene panel to predict the OS of LUAD, which may contribute to predicting prognosis accurately and making the clinical decisions of individual therapy for LUAD patients.

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A RNA sequencing-based six-gene signature for survival prediction in patients with glioblastoma

Cited by 50 publications

References 51 publications

Longer-term (≥ 2 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: a systematic review and meta-analysis

Longer-term (≥ 2 years) survival in patients with glioblastoma in population-based studies pre- and post-2005: a systematic review and meta-analysis

Identification of a four-gene panel predicting overall survival for lung adenocarcinoma

Identification of a four‑gene panel predicting overall survival for lung adenocarcinoma

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