Background: Aberrant patterns of microRNA expression have been highlighted as a potential clinical biomarker in breast cancer as the most frequent cancer among women that contributes nearly a quarter of total cancer incidence in 2018. Upregulation of microRNA-21 (miR-21) is associated with adverse clinical outcomes in breast cancer. However, the use of circulating free miR-21 as a non-invasive biomarker for diagnosis and therapeutic monitoring in breast cancer is not well established. We quantified the levels of circulating miR-21 expression and analyzed their correlation with clinicopathological variables and progression-free survival. Materials and Methods: This initial study included a cohort of 102 breast cancer patients of different subtypes and clinicat stages. We also included 15 unrelated healthy women. Venous blood from patients was collected at diagnosis and after treatment of surgery and chemotherapy. MiR-21 expression was quantified from total RNA fraction isolated from patient's plasma. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyzed miR-21 expression. Results: Expression of circulating miR-21 was significantly elevated in breast cancer patients compared to healthy women (median miR-21 expression levels were 7.67±2.2 and 1.28±0.16, respectively; p<0.0001). Significant reduction of miR-21 expression was observed in breast cancer patients after completion of surgery and chemotherapy (median miR-21 expression levels were 7.67±2.2 at diagnosis and 2.16±1.28 after treatment, respectively; p<0.0001). MiR-21 expression was higher in breast cancer patients younger than 40-year-old but was not significantly different according to different histopathological grades and clinical stages at diagnosis. Patients with upregulation of circulating miR-21 were associated with poor progression-free survival (median survival 72 vs 86 weeks, respectively; log-rank (Mantel-Cox) test, p=0.049). Conclusion: MiR-21 expression was upregulated in breast cancer patients and might serve as a therapeutic monitoring marker.
Background: Breast cancer incidence rates have been continuously increasing in majority nations with significant higher portion of cancer-related mortality in low-and middle-income countries. Developing new biomarker is an emerging field in the breast cancer research. Application of a promising minimally invasive biomarker, circulating microRNA, for additional improvement of diagnosis, prognosis, and therapeutic monitoring in breast cancer is not well corroborated. Materials and Methods: To uncover the potential use of circulating miR-155 expression as a clinical biomarker in breast cancer, we analyzed 102 breast cancer patients at diagnosis and after treatment as well as 15 healthy women. Total RNA was isolated from patient's plasma and expression of circulating miR-155 was measured with quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression levels of circulating miR-155 were compared according to the effect of treatment, clinicopathological variables, and progression-free survival. Results: In comparison to the healthy women, expression of circulating miR-155 levels were significantly higher (medians were 18.49±19 and 1.28±0.18, respectively; p<0.0001). The expression levels of miR-155 were significantly diminished after patients completed surgery and chemotherapy (medians were 18.49±19 at diagnosis and 1.32±0.22 after treatment, respectively; p<0.0001). Patients older than 40 years old expressed higher circulating miR-155 than those younger than 40 years-old (medians were 28.92±22 and 4.19±2.49, respectively; p<0.0001). Circulating miR-155 was significantly higher in patients with tumors larger than 5 cm (44.27±2.6 vs 9.17±6.9, p=0.03). MiR-155 expression levels were not significantly different according to various tumor grades, subtypes, and clinical stages. Although longer follow-up is required, progression-free survivals of patients with upregulation of circulating miR-155 were significantly longer (mean survivals were 77 and 65 weeks, Log-rank (Mantel-Cox) test p=0.038). Conclusion: Expression of circulating miR-155 expression was significantly elevated in breast cancer patients and was decreased after treatment. Therefore, circulating miR-155 is potentially applicable as diagnostic therapeutic monitoring marker in breast cancer.
Ovarian cancer is a lethal disease. One of the problems faced by patients with ovarian cancer is the lack of symptoms in its early stages, which results in it only being detected when it is at an advanced stage. Therefore, there is an urgent need for biomarkers that can predict ovarian cancer precisely. The purpose of this study was to determine the expression of microRNA-21 as a predictive biomarker candidate in both early- and advanced-stage ovarian cancer. This was a cross-sectional study using the blood plasma of 21 healthy control subjects and 37 blood plasma samples from patients with ovarian cancer. Blood plasmas were collected, from which the RNA was isolated. Based on the RNA, the cDNA was synthesized and run through qPCR, the results of which were analyzed using the Livak method. The results showed an upregulation of microRNA-21 in the advanced stage by 2.14 fold compared with the early stage, and 6.13 fold compared with the healthy controls (p < 0.05). The upregulation of microRNA-21 in early-stage ovarian cancer was 2.86 fold compared with the healthy control subjects (p < 0.05). In addition, there was an increase in the expression of microRNA-21 in ovarian cancer by 4.14 fold compared with the healthy controls (p < 0.05). Based on these results, it can be concluded that the expression of microRNA 21 upregulated with the severity of the disease.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and the third leading cause of cancer-related deaths worldwide. HCC carries poor prognosis, its incidence and mortality increase annually. The most common hypothesis explaining the problem is the cell's high tendency to metastasize and recur, even after surgical treatment. Therefore, it is important to find new serological biomarkers to detect HCC in early stages. Plasma microRNAs are being actively investigated as minimallyinvasive biomarkers in HCC as well as other human cancers. This study is aimed to investigate the level of expression of miR-21, miR-29c, and miR-155 as novel serological biomarkers for hepatocellular carcinoma. This study is preliminary quasi experimental study, and further sample collection is still underway. This study involved 8 HCC patients and 8 healthy controls. Blood sample of HCC patients were obtained from RSUP dr. Sardjito, Yogyakarta, and the patients were selected according to specific inclusion and exclusion criteria. The collected blood samples were treated as follows: plasma isolation, RNA total isolation, cDNA synthesis, quantification by qRT-PCR, data analysis with Biorad CFX ManagerTM Softwere to determine Cq, followed by the calculation of expression levels using Livax Methods. The result revealed that miR-21 and miR-155 were upregulated, 1.68 fold and 2.38 fold respectively, compared to healthy control. Secondly, miR-29c was downregulated (3,45 fold) compared to healthy control. Based on the result of preliminary study, we concluded that miR-21 acts as oncomiR, while miR-29c and miR-155 act as tumor supressor miR in HCC. The three microRNAs might be detected in HCC and might be used as minimally-invasive biomarkers in HCC detection.
Breast cancer has emerged as the most common cancer-related mortality among women worldwide. Therefore, early cancer detection using biomarkers such as microRNA is required. One of microRNAs that has an important role in breast cancer development is miR-155. Hsa-miR-155-5p is an oncomiR that is commonly dysregulated in breast cancer. This study aims to determine the expression of hsa-miR-155-5p in breast cancer patient's plasma before and after chemotherapy. We collected 64 samples from breast cancer patients admitted to Dr. Sardjito Hospital in Yogyakarta. RNA from plasma was extracted using RNA Isolation Kit miRCURY-Biofluid. cDNA synthesis was performed using cDNA Synthesis kit II and quantification of miR-155-5p using ExiLent SYBR Green master mix (Exiqon). qRT-PCR results were then analyzed with Livak's method and compared (before and after chemotherapy) to t-test. Expression of miR-155-5p in the breast cancer patients' plasma after chemotherapy was significantly increased (10.59 times) when compared to before chemotherapy (p = 0.001). We concluded that there was upregulated expression of miR-155-5p after chemotherapy than before chemotherapy. There has not been a known, relevant pathway between hsa-miR-155-5p and chemotherapy regimens nor its impact on resistance to chemotherapy.
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