Biomarker: MicroRNAs
Here you can find our research results dealing with investigation of microRNAs as biomarker.
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MicroRNAs as biomarker
MicroRNAs (miRNAs) are small, non-coding RNA molecules being important key players in the regulation of fundamental biological processes such as:
- proliferation
- differentiation
- cell cycle
- cell death (apoptosis)
MiRNAs bind to messengerRNAs (mRNA) and thereby inducing either an inhibition or degradation of the mRNA resulting in a downregulation of the protein level. Until now, more than 2000 miRNA were identified, regulating about 1/3 of all protein-coding genes. Thus, a dysregulation of miRNAs is associated with carcinogenesis, metastasis and therapy resistance. Studies have shown that miRNAs are usable as prognostic biomarker as well as new therapeutic targets.
Project: analysis of miRNA expression in locally advanced HNSCC
Tumor tissue from patients with locally, advanced head and neck carcinomas was collected, subjected for miRNA isolation and expression profile analyzed . This material was collected within the ARO-04-01 study and preserved for further analysis. The included patients received fractional radiotherapy in combination with two different chemotherapies (mitomycin C or cisplatin) aiming to compare the efficacy of both strategies. Another aim of this study was the identification and characterization of patient groups which would benefit most from one or the other therapy.
In our laboratory, miRNA was isolated from this preserved tissue samples and their expression level was analyzed by using a microarray technology (Affymetrix, Thermo Fisher Scientific). Based on these data, nine miRNAs were identified which showed different expression levels between the two patient groups. Therefore, patients were classified as well responders or non-/poor-responders for the respective treatment. Of these nine identified miRNAs, three showed a particularly strong correlation with the overall survival (OS) of patients, whereby an increased expression is associated with a poor OS.
In summary, this project has revealed a significant correlation between miRNA expression profile and therapy efficacy for oropharynx carcinoma. In particular, the overexpression of miRNA-200 is associated with better survival and less distant metastasis after mitomycin C treatment and the overexpression of miRNA-155 correlates with better survival and fewer local recurrences after cisplatin treatment. Furthermore, the miRNAs miR155 and miR146a were identified as so-called surrogate markers for tumor-infiltrating lymphocytes, which could provide a predictive information on the response of chemoradiotherapy and its combination with immune checkpoint inhibitors.
project aims
- Concordance between expression profile of certain miRNAs and clinical progress
- Identify miRNAs and their impact (positive/negative) on the disease progression
- Determine whether there is any correlation between HPV status and expression of certain miRNAs and if so, how do they impact the clinical outcome
further literature
- Authors:Hess AK, Müer A, Mairinger FD, Weichert W, Stenzinger A, Hummel M, Budach V, Tinhofer
Journal:Eur J Cancer Year:2017; Volume:77:Pages:3-12.
Title:MiR-200b and miR-155 as predictive biomarkers for the efficacy of chemoradiation in locally advanced head and neck squamous cell carcinoma. - Authors:Chen X, Liang H, Zhang J, Zen K, Zhang CY
Journal:Protein Cell Year:2012; Volume:3Issue:(1):Pages:28-37.
Title:Horizontal transfer of microRNA: molecular mechanisms and clinical applications - Authors:Taylor DD, Gercel-Taylor C
Journal:Gynecol Oncol Year:2008; Volume:110Issue:(1):Pages:13-21.
Title:MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer - Authors:Zhao L, Bode AM, Cao Y, Dong Z
Journal:Carcinogenesis Year:2012; Volume:33Issue:(11):Pages:2220-2227.
Title:Regulatory mechanisms and clinical perspectives of miRNA in tumor radiosensitivity
