Plasma micrornas as a biomarker for detection of colorectal cancer in Hospital Universiti Sains Malaysia
Colorectal cancer (CRC) is one of the cancer with a low survival rate and usually end with death. Colonoscopy is currently the gold standard in detecting CRC disease. However, due to the inconvenience of the procedure, it becomes less appealing. Since its discovery, microRNA (miRNA) has pioneered...
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| Format: | Thesis |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | http://eprints.usm.my/60394/1/Syarah%20Syamimi%20Mohamed-E.pdf |
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| Summary: | Colorectal cancer (CRC) is one of the cancer with a low survival rate and
usually end with death. Colonoscopy is currently the gold standard in detecting CRC
disease. However, due to the inconvenience of the procedure, it becomes less
appealing. Since its discovery, microRNA (miRNA) has pioneered a new era of
molecular diagnosis. MiRNA is a short post-transcriptional regulatory that targets
messenger RNA (mRNA), either causing degradation or altering the protein
translation. MiRNA expression is dysregulated in CRC tissue. The presence of
miRNAs in plasma is thought to provide non-invasive screening tools for detecting
disease and may aid early detection. Even though many miRNAs have been profiled
in CRC, there is still ambiguity on the robustness of the reported miRNAs in detecting
CRC. Thus, a miRNA expression study was conducted using a population sample in
Hospital Universiti Sains Malaysia to search for potential circulating miRNAs as CRC
screening biomarkers. The significant miRNA profile in CRC tissue was obtained by
comparing their expression to its adjacent normal tissue. A few upregulated miRNAs
from tissue (hsa-miR-20a-5p, hsa-miR-21-5p, and hsa-miR-210-3p) were validated in
their plasma and other independent study groups (CRC and healthy individuals).
Relatively, among these three miRNAs, hsa-miR-21-5p (FC=3.87) has the highest fold
change (FC) in the plasma of CRC patients compared to healthy individuals, followed
by hsa-miR-20a-5p (FC=1.23) and hsa-miR-210-3p (FC=-0.21). However, expression
of hsa-miR-210-3p in plasma was inconsistent as compared to tissue. According to
Spearman correlation analysis, hsa-miR-21-5p has a strong positive correlation (r=0.84) compared to hsa-miR-20a-5p (r=0.20). Meanwhile, hsa-miR-210-3p showed
a negative correlation (r=-0.75) between tissue and plasma. Lastly, we evaluated the
diagnostic performance of individual and combined miRNAs using receiver operating
characteristics curve analysis according to stages. Our studies revealed that hsa-miR-
20a-5p (AUC: 0.82, 86% sensitivity and 88% specificity) potentially act as a
biomarker panel for early CRC, whereas both hsa-miR-21-5p and hsa-miR-210-3p
(AUC: 1.0, 100% sensitivity and specificity simultaneously) are for advanced CRC.
Combining all three miRNAs also gives good discriminative power (AUC:0.98)
between CRC patients and healthy individuals with 96% sensitivity and 75%
specificity. Meanwhile, the combination of two miRNAs, namely hsa-miR-21-5p and
hsa-miR-210-3p, and hsa-miR-20a-5p and hsa-miR-21-5p, resulting in discrimination
power of 0.97 and 0.91, respectively. The study discovered three circulating miRNAs,
hsa-20a-5p, hsa-miR-21-5p, and hsa-210-3p, which may be minimally invasive
diagnostic biomarkers. Hsa-miR-21-5p and hsa-miR-210-3p have strong positive and
negative correlations with their tissue counterparts. In conclusion, individual hsa-miR-
21-5p has the highest discriminative power, while combined miRNAs showed that
combining all three was the best combination with the highest discriminatory power. |
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