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Published on: March 14, 2019
Analysis of MicroRNA Expression Changes During the Course of Therapy In Rectal Cancer Patients
Klara Cervena1,2, Vendula Novosadova3, Barbara Pardini4,5
1Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czechia.
Abstract:
MicroRNAs (miRNAs) regulate gene expression in a tissue-specific manner. However, little is known about the miRNA expression changes induced by the therapy in rectal cancer (RC) patients. We evaluated miRNA expression levels before and after therapy and identified specific miRNA signatures reflecting disease course and treatment responses of RC patients. First, miRNA expression levels were assessed by next-generation sequencing in two plasma samplings (at the time of diagnosis and a year after) from 20 RC patients. MiR-122-5p and miR-142-5p were classified for subsequent validation in plasma and plasma extracellular vesicles (EVs) on an independent group of RC patients (n=107). Due to the intrinsic high differences in miRNA expression levels between samplings, cancer-free individuals (n=51) were included in the validation phase to determine the baseline expression levels of the selected miRNAs. Expression levels of these miRNAs were significantly different between RC patients and controls (for all p <0.001). A year after diagnosis, miRNA expression profiles were significantly modified in patients responding to treatment and were no longer different from those measured in cancer-free individuals. On the other hand, patients not responding to therapy maintained low expression levels in their second sampling (miR-122-5p: plasma: p=0.05, EVs: p=0.007; miR-142-5p: plasma: p=0.008). Besides, overexpression of miR-122-5p and miR-142-5p in RC cell lines inhibited cell growth and survival. This study provides novel evidence that circulating miR-122-5p and miR-142-5p have a high potential for RC screening and early detection as well as for the assessment of patients' outcomes and the effectiveness of treatment schedule.
Insights
Circulating microRNAs (miRNAs), specifically miR-122-5p and miR-142-5p, show promise as biomarkers for rectal cancer (RC) screening, early detection, and treatment response assessment. Their levels normalize in patients responding to therapy, unlike non-responders.
Area of Science:
- Oncology
- Molecular Biology
- Biomarkers
Background:
- Rectal cancer (RC) treatment response monitoring is crucial for patient outcomes.
- MicroRNAs (miRNAs) are key gene regulators, but their role in RC therapy response is not well understood.
- Identifying reliable biomarkers for early detection and treatment assessment in RC is a significant clinical need.
Purpose of the Study:
- To evaluate miRNA expression changes in rectal cancer (RC) patients before and after therapy.
- To identify specific miRNA signatures that reflect disease course and treatment responses.
- To assess the potential of circulating miRNAs as biomarkers for RC screening, early detection, and treatment effectiveness.
Main Methods:
- Next-generation sequencing of plasma miRNA expression in 20 RC patients at diagnosis and one year later.
- Validation of miR-122-5p and miR-142-5p in plasma and extracellular vesicles (EVs) of 107 RC patients and 51 controls.
- Comparison of miRNA expression levels between RC patients and controls, and correlation with treatment response.
Main Results:
- Significant differences in miR-122-5p and miR-142-5p expression between RC patients and controls (p <0.001).
- MiRNA expression profiles normalized to control levels in patients responding to therapy after one year.
- Non-responding patients maintained low miRNA levels, with significant differences observed in plasma and EVs.
- Overexpression of these miRNAs in RC cell lines inhibited cell growth and survival.
Conclusions:
- Circulating miR-122-5p and miR-142-5p are significantly altered in rectal cancer patients.
- These miRNAs serve as potential biomarkers for assessing treatment response and patient outcomes in RC.
- The findings support the use of miR-122-5p and miR-142-5p for RC screening, early detection, and monitoring treatment effectiveness.
