PhD Scientific Days 2017

Poster Presentation: Oncology

P35: Analysis of SFRP1, SFRP2, SDC2 and PRIMA1 promoter methylation for colorectal adenoma and cancer detection in plasma samples

Előadó neve

Barták, Barbara Kinga

Előadó munkahelye

2nd Department of Internal Medicine, Semmelweis University

Előadó telefonszáma

+36302635051

Előadó e-mail címe

bartak.barbara@gmail.com

Az előadás címe

Analysis of SFRP1, SFRP2, SDC2 and PRIMA1 promoter methylation for colorectal adenoma and cancer detection in plasma samples

Szerző(k) neve és munkahelye

Barbara Kinga Barták1, Alexandra Kalmár1, Bálint Péterfia1, Árpád V. Patai1, Orsolya Galamb2, Gábor Valcz2, Barnabás Wichmann2, Zsófia Brigitta Nagy1, Kinga Tóth1, Zsolt Tulassay2, Béla Molnár2
1 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
2 Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest, Hungary

Szekció

Poster Presentation: Oncology

Data of the presenter

Doctoral School: Clinical Medicine
Program: Gastroenterology
Supervisor: Béla Molnár
E-mail: bartak.barbara@gmail.com
poster

Text of the abstract

Aberrant DNA methylation is one of the most frequent epigenetic alterations, which can influence gene expression and contribute to tumor formation. Cell-free DNA can originate from tumor tissue; therefore the evaluation of tumor-related DNA methylation markers in plasma can be a promising method for cancer screening. Our aim was to analyse the methylation pattern of four selected genes along colorectal adenoma-carcinoma sequence in both colon tissue and plasma.
Methylation-specific PCR was used to study certain DNA sequences of the promoter regions of SFRP1, SFRP2, SDC2 and PRIMA1 in plasma and matched biopsy samples. For validation of our results on biopsy samples, previous methyl capture sequencing data was bioinformatically reanalysed. Furthermore, the methylation status of the four candidates’ whole promoter regions was examined using Illumina Infinium HumanMethylation450 BeadChip methylation array data downloaded from The Cancer Genome Atlas (TCGA) database and from NCBI Gene Expression Omnibus Database (GEO accession number: GSE48684). The effect of altered promoter methylation pattern on the protein expression was analysed by immunohistochemistry analysis.
Using MSP, methylation of SFRP1, SFRP2, SDC2 and PRIMA1 was observed in 85.1%, 72.3%, 89.4% and 80.9% in the plasma fraction of patients with CRC and 89.2%, 83.8%, 81.1% and 70.3% of adenoma patients, respectively. Using combined analysis, the four markers together were able to distinguish CRC patients from normal individuals with 91.5% sensitivity and 97.3% specificity (AUC=0.978), and could differentiate adenoma samples from healthy controls with 89.2% sensitivity and 86.5% specificity (AUC=0.937). In silico analysis confirmed our results on the altered methylation pattern of the four markers. Immunohistochemistry analysis indicated decreasing protein levels of the four markers along the colorectal adenoma-carcinoma sequence.
In conclusion, the present study offers the possibility that the detection of selected methylation markers in plasma of colorectal adenoma and cancer patients can become a non-invasive, epigenetic diagnostic test.

Azonosító

P35

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1159

Authors (legacy)

Barbara Kinga Barták1, Alexandra Kalmár1, Bálint Péterfia1, Árpád V. Patai1, Orsolya Galamb2, Gábor Valcz2, Barnabás Wichmann2, Zsófia Brigitta Nagy1, Kinga Tóth1, Zsolt Tulassay2, Béla Molnár2
1 2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
2 Molecular Medicine Research Group, Hungarian Academy of Sciences, Budapest, Hungary