Pancancer survival analysis of cancer hallmark genes

Cancer hallmark genes are responsible for the most essential phenotypic characteristics of malignant transformation and progression. In this study, our aim was to estimate the prognostic effect of the established cancer hallmark genes in multiple distinct cancer types. RNA-seq HTSeq counts and survi...

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Vydáno v:Scientific reports Ročník 11; číslo 1; s. 6047 - 10
Hlavní autoři: Nagy, Ádám, Munkácsy, Gyöngyi, Győrffy, Balázs
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 15.03.2021
Nature Publishing Group
Nature Portfolio
Témata:
631/67/1857
631/67/395
631/67/69
Angiogenesis
Bladder cancer
Brain tumors
BRCA1 protein
Cancer
Cell death
Cervical cancer
Cervix
Deregulation
Gene expression
Genomes
Genomic instability
Glioblastoma
Glioma
Glioma cells
Heterogeneity
Humanities and Social Sciences
Kidneys
Metastases
multidisciplinary
Myc protein
Renal cell carcinoma
Runx1 protein
Science
Science (multidisciplinary)
Solid tumors
Survival
Survival analysis
Thyroid
Thyroid cancer
Tumor suppressor genes
ISSN:2045-2322, 2045-2322
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Shrnutí:Cancer hallmark genes are responsible for the most essential phenotypic characteristics of malignant transformation and progression. In this study, our aim was to estimate the prognostic effect of the established cancer hallmark genes in multiple distinct cancer types. RNA-seq HTSeq counts and survival data from 26 different tumor types were acquired from the TCGA repository. DESeq was used for normalization. Correlations between gene expression and survival were computed using the Cox proportional hazards regression and by plotting Kaplan–Meier survival plots. The false discovery rate was calculated to correct for multiple hypothesis testing. Signatures based on genes involved in genome instability and invasion reached significance in most individual cancer types. Thyroid and glioblastoma were independent of hallmark genes (61 and 54 genes significant, respectively), while renal clear cell cancer and low grade gliomas harbored the most prognostic changes (403 and 419 genes significant, respectively). The eight genes with the highest significance included BRCA1 (genome instability, HR 4.26, p < 1E−16), RUNX1 (sustaining proliferative signaling, HR 2.96, p = 3.1E−10) and SERPINE1 (inducing angiogenesis, HR 3.36, p = 1.5E−12) in low grade glioma, CDK1 (cell death resistance, HR = 5.67, p = 2.1E−10) in kidney papillary carcinoma, E2F1 (tumor suppressor, HR 0.38, p = 2.4E−05) and EREG (enabling replicative immortality, HR 3.23, p = 2.1E−07) in cervical cancer, FBP1 (deregulation of cellular energetics, HR 0.45, p = 2.8E−07) in kidney renal clear cell carcinoma and MYC (invasion and metastasis, HR 1.81, p = 5.8E−05) in bladder cancer. We observed unexpected heterogeneity and tissue specificity when correlating cancer hallmark genes and survival. These results will help to prioritize future targeted therapy development in different types of solid tumors.
Bibliografie:ObjectType-Article-1
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-84787-5