PhD Scientific Days

Poster Presentation: Oncology

P38: Effect of combined mutational fingerprint of ERBB receptor family on survival in non-small cell lung cancer

Előadó neve

Nagy, Ádám

Előadó munkahelye

MTA TTK Lendület Cancer Biomarker Research Group, Magyar Tudósok körútja 2., 1117, Budapest, Hungary

Előadó telefonszáma

+3630 287-9757

Előadó e-mail címe

nagy.adam@ttk.mta.hu

Az előadás címe

Effect of combined mutational fingerprint of ERBB receptor family on survival in non-small cell lung cancer

Szerző(k) neve és munkahelye

Ádám Nagy1,2, Lőrinc Sándor Pongor1,2, Győrffy Balázs1,2
1 MTA TTK Lendület Cancer Biomarker Research Group, Magyar Tudósok körútja 2., 1117, Budapest, Hungary
2 Semmelweis University 2nd Dept. of Pediatrics, Budapest, Hungary

Szekció

Poster Presentation: Oncology

Data of the presenter

Doctoral School: Pathology
Program: Oncology
Supervisor: Dr. Balázs Győrffy
E-mail address: zsalab2@yahoo.com

Text of the abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung tumors accounting for approximately 85% of all lung cancer cases. In NSCLC, the most important mutated genes include EGFR, ALK, VEGFR2, and KRAS which serve as predictive markers and play crucial role in targeted anticancer therapy. EGFR is a member of the ERBB family, which also includes ERBB2, ERBB3 and ERBB4. The prognostic role of these genes’ mutation status in NSCLC still remains controversial. Here, our aim was to examine the effect of mutational transcriptomic fingerprint established after combining ERBB family members on survival in NSCLC.

We utilized raw exome sequencing data from TCGA. We identified somatic mutations using MuTect. Gene expression data – RNAseq and Affymetrix – was obtained from TCGA and NCBI GEO, respectively. We applied DESeq and MAS5 algorithms to normalize the raw expression data. We designated a metagene as the mean expression of genes correlated with EGFR, ERBB2, ERBB3 and ERBB4 mutation status by performing Mann-Whitney-Wilcoxon analysis. Furthermore, we examined the correlation of expression with survival for each ERBB gene signature and their combinations using Cox proportional hazards regression and by plotting Kaplan-Meier survival plots.

We processed the exome sequencing and RNA-seq data of 994 TCGA samples, as well as 2,437 samples with gene chip data. We found that mutation and expression of the ERBB family genes per se had minimal prognostic value. On the other hand, when examining the transcriptomic signatures, prognostic value was significant for signatures of EGFR, ERBB2, ERBB3 and ERBB4. The best prognostic power was obtained when we examined the combined signature of all ERBB family members.

We generated surrogate signature of ERBB mutation status in NSCLC patients by linking genotype and gene expression. The combination of multiple ERBB family members had an improved prognosis prediction power compared to single gene based classifiers.

Azonosító

P38

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1201

PhD Scientific Days 2017

Budapest, 11-12 April 2017