Hjem
Klinisk institutt 1

Midtveisevaluering - Saroj Rajthala

Midtveisevaluering for ph.d.-graden ved Universitetet i Bergen for kandidat Saroj Rajthala.

Hovedinnhold

Abstract:

microRNA deregulation in oral cancer stroma-role in oral cancer progression and prognostication

Introduction
Epithelial-stromal interactions play a crucial role in progression of human cancer. It has been shown in many different types of human cancers including oral squamous cell carcinoma that the fibroblasts, the most abundant cell type of the cancer stroma plays a major role for the development, invasion and metastasis of cancer. Recent studies have shown the association of aberrant expression of micro-RNAs (miRNAs) in tumour-associated stroma with cancer progression.  This study aims to investigate miRNA as potential biomarkers in oral cancer and find the role of miRNAs in oral cancer development and progression.

Method:
Primary fibroblast cultures- cancer associated fibroblasts (CAFs) and normal oral fibroblasts (NOFs) were generated from fresh tissue biopsies of oral cancer patients and healthy individuals (buccal mucosa) respectively. Total RNA from fibroblast cultures were extracted and miRNA expression was profiled using Illumina version 2 panels and using SAM analysis.  Significantly differentially regulated miRNAs were validated by qRT-PCR. miRNA expression was further investigated by in situ hybridization (ISH) in tissues of (formalin fixed paraffin embedded/FFPE) oral cancer patients.

Results:
We have found differential regulation of miRNAs in between CAFs and NOFs. miR-138-5p, miR-378-3p, miR190b and miR-582-5p are the miRNAs  significantly upregulated in CAFs, while miR-224-5p, miR-16-2*,  miR-155-5p, miR92b, miR-204-5p, miR-504-5p, miR-1270, and miR-3611 are the ones significantly down regulated in CAFs compared to  NOFs. In situ expression in oral cancer tissues also shows differential expression of miRNAs in the cancer compartment compared to the normal counterpart. 

Conclusion:
The study shows deregulation of stromal miRNAs as a major event in oral cancer, and therefore the miRNAs could potentially be used as biomarkers in oral cancer.