Airlangga University Hematology-Medical Oncology Research Team Unravel the Role of Plasma Micro RNA-21 (miRNA-21) as a Novel Breast Cancer Biomarker in Indonesian Population

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miRNA-21 and Breast Cancer. (Images: personal documentation)
miRNA-21 and Breast Cancer. (Images: personal documentation)

Breast cancer is known as the most prevalent cancer in women with its profound mortality and morbidity, both around the world and in Indonesia. In a larger scope breast cancer also burdens economic, social, and psychological aspects. The management of breast cancer patient needs a comprehensive approach from multidiscipline team and aspects. Breast cancer patient care could be divided into several aspects including prevention, early screening, diagnostic, treatment, monitoring, education, and palliative care. Therefore a versatile, minimal-invasive, sensitive, and specific marker is needed to give a better management of breast cancer patients.

Cancers are caused by uncontrolled cell division that caused by genetic defect and could eventually lead to mortality. This concept has been explored further, as the genetics is not only limited in the genomic DNA, however a vast amount of other complex also plays a different role in gene expression. Genomic DNA possess genetic information of living beings, however according to the central dogma these genetics pattern or genotype are not always expressed in the cells and organism. There are various factors involved in genetic expression between genomic sequences, transcripted sequences, and translated sequences. In the recent development it is suggested that there are vast amount of epigenetic mechanism that regulated gene expression dynamics.

Epigenetic mechanism needed a further in depth analysis and exploration as these aspects are known to play pivotal role in genotype-phenotype interactions. Micro RNA or mirna is one of the epigenetics factors that regulate gene expression. Mirna act as the regulator of gene expression mainly by binding with messenger RNA (mRNA) thus degrading the mRNA that results in the post transcription modulation of gene expression (silencing). This mechanism could disrupt cellular homeostasis mechanism of cell death and cell division if it interacts with cell death and cell division related gene expression. Oncology is the branch of medicine that studies ,cancer biology could divide miRNA into oncogenic miRNA (oncomir) and anti-oncogenic miRNA (tumor suppressing-mir). As a epigenetic factors, miRNA changes tend to occur before gene expression changes and cancer are begin to occur and metastasized.

One of a routinely used tumor marker in breast cancer is CA-15-3 or carbohydrate antigen 15-3, this marker is a plasma marker routinely used as a disease progression marker and breast cancer-monitoring tool. However, this widely available marker still lacks specificity and sensitivity, as it tends to increase in other malignancy and liver-related diseases.

Based on this issue, Hematology-Medical Oncology Division Research Team of Internal Medicine Department, Faculty of Medicine, Airlangga University leaded by Merlyna Savitri, dr., Sp.PD-KHOM, coordinated by Prof. Dr. Ami Ashariati, dr., Sp.PD-KHOM, FINASIM enrolled a clinical research to confirm this facts and aiming to explore miRNA roles in clinical settings.

MiRNA-21 is one of the miRNA that act as an oncomir by targeting and silencing several tumor suppressor genes including PTEN, Bcl-2 and PDCD4. Based on the previous studies all around the world, it is suggested that high expression of miRNA-21 correlates with disease progression, poor prognosis, with a relative well specificity and sensitivity in breast cancer.

This miRNA-21 study in breast cancer was performed in Airlangga University Hospital by collecting venous blood samples and comparing the miRNA-21 expression level with normal volunteers through reverse transcript quantitative polymerase chain reaction (RT-qPCR) that was performed in partnership with Prodia Clinical Laboratory. There were 49 breast cancer subjects and 16 healthy volunteers who participated in this study.

In this study dr. Merlyna Savitri and team found that in Indonesian population miRNA-21 expression from plasma as minimal-invasive methods suggested that miRNA-21 could be utilized as breast cancer disease progress monitoring marker, and exhibit decent 91.8% sensitivity and 87.5 % specificity compared to CA 15-3 (59.2% sensitivity, and 62.5% specificity).

These results indicated that miRNA-21 could serve as a breast cancer diagnostic and disease-progression monitoring tool with minimal-invasive approach and decent specificity and sensitivity in the future. Moreover, Prof. Ami Ashariati and team stated that exploration of miRNA-21 expression role should be further assessed as it might be involved in breast cancer prognosis and breast cancer relapse predictor with a larger sample or even in multi-center approach to more precisely pinpoint miRNA-21 utilization in clinical settings.

This study has been published in The Indonesian Biomedical Journal and could be accessed at https://inabj.org/index.php/ibj/article/view/1142. The authors hope that this study might offers insight and inspire as the foundation for future study especially in the filed of oncology and epigenetics.

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Author: Andi Yasmin Wijaya

Editor: Feri Fenoria

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