Circulating Plasma miRNA-21 as a Superior Biomarker Compared to CA 15-3: Assessment in Healthy Age Matched Subjects and Different Stage of Breast Cancer Patients

BACKGROUND: Carbohydrate antigens 15-3 (CA 15-3) is a conventional tumor marker in breast cancer, with low sensitivity and specificity. MicroRNA (miRNA)-21 showed its stability in circulation and could serve as powerful biomarker. The aim of this study was to evaluate miRNA-21 as breast cancer biomarker compared to CA 15-3 in Indonesian population.METHODS: Circulating plasma miRNA-21 expression was measured using qRT-PCR in 49 patients at various stages of breast cancer and 16 healthy controls. The relative expression value of miRNA-21 was calculated using 2-ΔΔCt. Meanwhile, CA 15-3 was quantified using electrochemiluminescence immunoassay (ECLIA) methods. The results of miRNA-21 and CA 15-3 plasma circulating expression were compared with controls at each stage and between stages of breast cancer.RESULTS: CA 15-3 median level in breast cancer group was 1.60 times higher compared to control group (p=0.019), 21.00 m/mL and 13.05 m/mL, respectively. Median miRNA-21 expression in breast cancer group was elevated 4.92 folds compared to control group (p=0.001), 4.43 and 0.90, respectively. There was no significant difference of CA 15-3 level between controls and all stages of breast cancer group. CA 15-3 cut-off value was 15.05 m/mL (p=0.016) with 59.2% sensitivity and 62.5% specificity. Meanwhile, there was a significant difference of miRNA-21 expression between controls and most stages of breast cancer group. Circulating miRNA-21 expression cut-off value was 2.07 (p=0.000) with 91.8% sensitivity and 87.5% specificity.CONCLUSION: Circulating miRNA-21 expression and CA 15-3 levels were significantly increased in breast cancer group compared to control group. The miRNA-21 expression increased consistently with breast cancer stage progression. miRNA-21 could serve as superior biomarker compared to CA 15-3.KEYWORDS: biomarker, breast cancer, circulating plasma, liquid biopsy, miRNA-2

Serum ferritin level affects T lymphocyte CD4, CD8, and CD4/CD8 ratio in transfusion-dependent beta-thalassemia

Background: Chronic blood transfusions and hemolysis are the major causes of secondary iron overloading transfusion- dependent beta-thalassemia. Iron overload can cause several organ complications including immune alteration. Infection due to immune alteration is number two leading cause of mortality in thalassemia. Research on the correlation of ferritin as iron overload marker and T lymphocyte subsets alteration in adult thalassemia patients are still rare and require further study. Objective: The objective of the study was to study the correlation of iron overload and T lymphocyte subsets CD4, CD8, and CD4/CD8 ratio in adult transfusion-dependent beta-thalassemia. Methods: The study was cross-sectional observational analytic study conducted on 36 subjects with transfusion-dependent beta-thalassemia diagnosed by clinical examination and laboratory high-performance liquid chromatography followed up at Hematology Clinic, Dr. Soetomo Teaching Hospital Surabaya, Indonesia. Ferritin serum was measured by chemiluminescence immunoassay method, while CD4, CD8 counts, and CD4/CD8 ratio were assessed by flow cytometry with antigen for CD3/CD4/CD8. Results: There were 36 subjects, 21 males and 15 females with median age of 23 (range 18–48). The mean ferritin serum was 5137.8 ± 2433.5 ng/ml while CD4, CD8, and CD4/CD8 ratio were 695.56 ± 25.17; 822.4 ± 360; and 0.95 ± 0.42, respectively. The analysis of correlation showed that there is correlation of ferritin and CD4 (r = ‒0.34, P < 0.05), ferritin and CD8 (r = 0.43, P < 0.05), and ferritin and CD4/CD8 ratio (r = 0.34, P < 0.05). Conclusion: In this study, there was a correlation between ferritin serum and CD4, CD8, and CD4/CD8 ratio. An increase of ferritin in iron overload will decrease CD4, increase CD8, and decrease CD4/CD8 ratio

Early detection breast cancer: role of circulating plasma miRNA-21 expression as a potential screening biomarker

Background/aim: To explore the potential of the circulating plasma miRNA-21 as an early detection biomarker by comparing earlystage breast cancer (BG) and healthy control (HG) in Indonesian population. Materials and methods: The enlisted patients were 26 adult female early-stage breast cancer patients (stage 1A, 1B, 2A, and 2B) of Airlangga University Hospital from August 2019 to October 2019. Sixteen volunteers were recruited as matching healthy subjects. MiRNA-21 expression was quantified by plasma qRT-PCR. Data analysis performed using IBM SPSS Statistics v.24 (IBM Corp., Armonk, NY, USA). MiRNA-21 cut-off, sensitivity, and specificity were analyzed using receiver operating characteristic (ROC) curve. Results: The study included 26 BG and 16 HG subjects. The miRNA-21 expression in BG group was 3.933 (1.181-11.794) and 0.905 (0.164-4.532) in HG group (4.34 folds; P = 0.001), with 1.66 cut-off (92.3% sensitivity; 81.2% specificity). MiRNA-21 expression separated analysis in HG showed a 0.578 times lower expression in menopause subjects [0.651 (0.164-0.414)], compared to premenopause ones [(1.123 (0.758 - 4.532); P = 0.031]. Yet, in BG group, 1.729 times higher miRNA-21 expression was observed in menopause subjects (6.021 ± 3.583), compared to premenopause ones (3.500 ± 1.517; P = 0.022). Conclusion: Circulating miRNA-21 expression is a potential biomarker for early detection of breast cancer and might act as a breast cancer risk predictor

Perbandingan Ekspresi Circulating Plasma miRNA-21 Dan CA 15-3 Pada Berbagai Stadium Klinis Kanker Payudara: Penelitian Observasional Analitik Cross-Sectional Divisi Hematologi Onkologi Medik di Unit Rawat Jalan RS UNAIR Surabaya

Latar belakang: Kanker payudara masih menempati peringkat pertama kanker pada wanita di dunia. Beberapa circulating biomarker konvensional yang sudah dikenal dan digunakan dalam monitoring dan menilai progresivitas kanker payudara seperti CEA dan CA 15-3 memiliki keterbatasan karena sensitivitas dan spesifisitas yang rendah. MicroRNA (miRNA) suatu non-coding RNA endogen dengan panjang 22-25 nukleotida, gen targetnya adalah kelompok gen tumor supresor, sehingga miRNA-21 dapat meregulasi proliferasi sel, transformasi neoplastik, migrasi sel, dan menurunkan apoptosis sel. Circulating biomarker baru seperti miRNA-21 menunjukkan peran yang besar dalam hal monitoring progresivitas kanker payudara. Tujuan: Menganalisis perbandingan antara ekspresi circulating miRNA-21 dan CA 15-3 pada berbagai stadium klinis kanker payudara. Metode: Dilakukan pengukuran ekspresi circulating plasma miRNA-21 dan CA 15-3 pada 49 pasien kanker payudara berbagai stadium dan 16 kontrol orang sehat menggunakan metode qRT-PCR dengan miRNA-16 sebagai kontrol endogen. Nilai ekspresi relatif miRNA-21 dihitung dengan formula 2-ΔΔCt. Hasil ekspresi circulating plasma miRNA-21 dan CA 15-3 dibandingkan dengan kontrol pada setiap stadium dan antar stadium kanker payudara. Hasil: Median kadar CA 15-3 pada kelompok kanker payudara secara signifikan lebih tinggi 1,60 kali dibandingkan dengan kelompok kontrol (p=0,019), masingmasing 21,00 u/ml (4,73-3000) dan 13,05 u/ml (5,2-19,9). Median ekspresi miRNA-21 pada kelompok kanker payudara secara signifikan lebih tinggi 4,92 kali dibanding kelompok kontrol (p=0,001), masing-masing 4,43 (1,11-32,22) dan 0,90 (0,16-4,53). CA 15-3 tidak bermakna pada perbandingan antara control dengan semua stadium kanker payudara dan antar stadium pada kelompok kanker payudara. Ekspresi circulating miRNA-21 bermakna pada perbandingan antar kontrol dengan kanker payudara stadium 1 (p=0,003), stadium 2 (p=0,001), dan stadium 4 (p=0,030). Nilai cut-off CA 15-3 sebesar 15,05 u/ml (p=0,016) dengan sensitivitas 59,2% dan spesifisitas 62,5%. Nilai cut-off ekspresi circulating miRNA-2 2,07 (p=0,000) dengan sensitivitas 91,8% dan spesifisitas 87,5%. Kesimpulan: Kadar CA 15-3 dan ekspresi circulating plasma miRNA-21 secara signifikan meningkat pada pasien kanker payudara dibandingkan dengan orang sehat. Terdapat peningkatan kadar CA 15-3 dan ekspresi miRNA-21 seiring bertambahnya stadium kanker payudara. MiRNA-21 merupakan suatu biomarker baru non-invasif yang potensial lebih baik dalam mendiagnosis dan memprediksi progresivitas kanker payudara dibandingkan CA 15-3

Autoimmune Hemolytic Anemia, Amoebic Dysentery, And Intracranial Hemorrhage as Rare Manifestations of Smoldering Multiple Myeloma: A Case Report

Background: Smoldering multiple myeloma (SMM) is in asymptomatic stages before overt multiple myeloma (MM) but it also has an increased risk of thrombosis, infection, autoimmune, and hemorrhage. SMM is usually recognized coincidentally during the workup of a variety of symptoms

Diagnostic Problem of Facial Malignancy in The Elderly: A rare case

Introduction: Lymphoma can occur in adults and the elderly, this will affect the condition of both diagnosis and therapy. Plasmablastic lymphoma (PBL) is a subtype of diffuse large B-cell lymphoma (DLBCL), the case is rarely found and often overlaps the anatomical pathology picture similar to plasmacytoma. It is aggressive and often relapses

The Association between Plasma miRNA-21 Levels with Overall 1-year Survival Rate of Breast Cancer Patients at Various Stages

Background: miRNA 21 exhibits an increased expression in breast cancer (BC). However, its relationship with the 1-year survival of breast cancer patients is still disputable and under serious discussion. Methods: Cohort prospective study involving 49 breast cancer patients was done, comprising 26 in early stage and 23 in end-stage. We evaluated miRNA-21 values and observed its association with mortality within 1 year. Results: In general, there was a correlation between the increase in miRNA-21 levels and the mortality rate of breast cancer patients (r = 0.651; p <0.05). In the early stages, the increase in miRNA-21 values was not associated with breast cancer mortality (r= 0.25; p=0.218), but in the later stages, we found that the increase in miRNA-21 had a correlation with mortality (r=0.866; p=<0, 05). In advanced stage, high level of miRNA-21 had high asscociation with mortality rate (HR 17,27 95%CI 7,37-40,69). Conclusion: The increase in miRNA-21 values is associated with the 1-year survival of breast cancer patients

Cardiac Tamponade: A Rare Manifestation of Lung Cancer. A Case Report

Background: Malignancy is the most common cause of non-inflammatory pericardial effusion that is usually neglected. Metastatic involvement of the pericardium is reflecting the advanced stage of the disease and generally associated with poor outcomes

Management and quality of life extranodal non hodgkin lymphoma of testis

Extranodal non-Hodgkin lymphoma still seems to be a rare case and an issue to discuss a lot. Clinical evidence and guidelines on treatment have not yet been widely published and accessible. We present a case of a forty-five-year-old male with the chief complaint of a bulky and huge right mass in the testis with an ulcer on it. The patient underwent an orchiectomy, and the biopsy showed a malignant round cell tumor, suspected as non-Hodgkin lymphoma. The patient then received the following treatment: chemotherapy with R-CHOP regiment every three weeks, consisting of 6 cycles showing shrinkage size of the testis by day 7 and final complete response after 4th cycle with ADE grade 0 no sexual activity disorder after chemotherapy. This raises hope in developing treatment modalities that the right choice on chemotherapy regimen with complete control on the drug effects may improve clinical outcome and patient’s quality of life

Increased hs-CRP and Sepsis Influence the Occurrence of Thrombocytopenia in Severe and Critically Ill COVID-19 Patients Receiving Anticoagulants

BACKGROUND: Despites its benefits, as one of COVID-19 principal treatments, anticoagulant raises a significant concern regarding the anticoagulant-related thrombocytopenia. However, up to date, there is lack of study examining anticoagulantinduced thrombocytopenia during COVID-19, hence this study was conducted to determine the factors inducing anticoagulant-induced thrombocytopenia in COVID-19 patients.METHODS: An observational cross-sectional study of 106 anticoagulant-treated COVID-19 subjects was conducted. Blood serum was drawn from subjects, then platelets, prothrombin time (PT), activated partial thromboplastin (aPPT), international ratio (INR), D-dimer, ferritin, fibrinogen, and high-sensitivity C-reactive protein (hs-CRP), were measured. For thrombocytopenia risk assessment, the 4T score was calculated. To assess the risk of thrombocytopenia. Statistical analysis using Chi-square and Mann-Whitney U test were performed and followed by multivariate analysis to examine the correlation among the thrombocytopenia risk factors.RESULTS: Significant differences were identified in the length of stay (LOS) (p=0.04), disease severity (p=0.021), sepsis (p=0.006), hs-CRP (p=0.003), and mortality rate (p=0.028) between thrombocytopenia and nonthrombocytopenia groups. A multivariate analysis through linear and logistic regression disclosed an increase in hs-CRP (OR=-0.29; p=0.045) and sepsis (OR=4.32; p=0.03) that precipitate the thrombocytopenia events.CONCLUSION: In severe and critically ill COVID-19 patients, the occurrence of thrombocytopenia was followed by an increase in inflammatory parameters such as D-dimer, fibrinogen, ferritin, hs-CRP and prolonged coagulation. The increase in hs-CRP and sepsis may raise the risk of thrombocytopenia, especially in severe and crtically ill cases of COVID-19.KEYWORDS: COVID-19, anticoagulant, thrombocytopenia, inflammation, infectious diseas