Pathology and Oncology III. Lectures
Nagy, Ádám
Semmelweis University Dept. of Bioinformatics and 2nd Dept. of Pediatrics
+36302879757
nagy.adam1@med.semmelweis-univ.hu
Tumor Associated Prognostic Biomarkers in Different Types of Tumors
Ádám Nagy1,2, Balázs Győrffy1,2
1 Semmelweis University Dept. of Bioinformatics and 2nd Dept. of Pediatrics, Tűzoltó utca 7-9., 1094, Budapest, Hungary
2 TTK Cancer Biomarker Research Group, Institute of Enzymology, Magyar Tudósok körútja 2., 1117, Budapest, Hungary
Pathology and Oncology III. Lectures
Hungarian
Pathology and Oncology
Molecular Sciences
Introduction & Aims
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.
Method
Raw 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.
Results
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.
Conclusion
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.
Supervisor: Prof. Dr. Balázs Győrffy
E-mail address: gyorffy.balazs@med.semmelweis-univ.hu
Szóbeli
Szabad
elfogadva
szóbeli
nem rendelkezett róla
4715
18:00
18:15
Ádám Nagy1,2, Balázs Győrffy1,2
1 Semmelweis University Dept. of Bioinformatics and 2nd Dept. of Pediatrics, Tűzoltó utca 7-9., 1094, Budapest, Hungary
2 TTK Cancer Biomarker Research Group, Institute of Enzymology, Magyar Tudósok körútja 2., 1117, Budapest, Hungary