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Chellan Kumarasamy

Bio: Chellan Kumarasamy is an academic researcher from University of Adelaide. The author has contributed to research in topics: Meta-analysis & Publication bias. The author has an hindex of 12, co-authored 51 publications receiving 381 citations. Previous affiliations of Chellan Kumarasamy include Charles Darwin University & SRM University.

Papers published on a yearly basis

Papers
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Journal ArticleDOI
01 Jun 2019-Medicine
TL;DR: This meta-analysis protocol examines the comparative utility of neutrophil-lymphocyte-ratio, platelet-ly mphocyte- ratio, and monocyte-lyymphocyte-Ratio as a simple, inexpensive, and effective method for cancer prognosis, in multiple cancers.

72 citations

Journal ArticleDOI
14 Oct 2019-Cells
TL;DR: A comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer suggests there are different mi RNAs involved in the regulation of chemores resistance through diverse drug genetic targets.
Abstract: Awareness of breast cancer has been increasing due to early detection, but the advanced disease has limited treatment options. There has been growing evidence on the role of miRNAs involved in regulating the resistance in several cancers. We performed a comprehensive systematic review and meta-analysis on the role of miRNAs in influencing the chemoresistance and sensitivity of breast cancer. A bibliographic search was performed in PubMed and Science Direct based on the search strategy, and studies published until December 2018 were retrieved. The eligible studies were included based on the selection criteria, and a detailed systematic review and meta-analysis were performed based on PRISMA guidelines. A random-effects model was utilised to evaluate the combined effect size of the obtained hazard ratio and 95% confidence intervals from the eligible studies. Publication bias was assessed with Cochran's Q test, I2 statistic, Orwin and Classic fail-safe N test, Begg and Mazumdar rank correlation test, Duval and Tweedie trim and fill calculation and the Egger's bias indicator. A total of 4584 potential studies were screened. Of these, 85 articles were eligible for our systematic review and meta-analysis. In the 85 studies, 188 different miRNAs were studied, of which 96 were upregulated, 87 were downregulated and 5 were not involved in regulation. Overall, 24 drugs were used for treatment, with doxorubicin being prominently reported in 15 studies followed by Paclitaxel in 11 studies, and 5 drugs were used in combinations. We found only two significant HR values from the studies (miR-125b and miR-4443) and our meta-analysis results yielded a combined HR value of 0.748 with a 95% confidence interval of 0.508-1.100; p-value of 0.140. In conclusion, our results suggest there are different miRNAs involved in the regulation of chemoresistance through diverse drug genetic targets. These biomarkers play a crucial role in guiding the effective diagnostic and prognostic efficiency of breast cancer. The screening of miRNAs as a theragnostic biomarker must be brought into regular practice for all diseases. We anticipate that our study serves as a reference in framing future studies and clinical trials for utilising miRNAs and their respective drug targets.

33 citations

Journal ArticleDOI
25 Jul 2019-Cells
TL;DR: Results indicate that miRNAs have potential clinical value as prognostic biomarkers in HNC, with miR-21, 125b, 34c-5p and 18a, in particular, showing great potential as progostic molecular markers.
Abstract: Head and Neck Cancer (HNC) is the sixth most common type of cancer across the globe, with more than 300,000 deaths each year, globally. However, there are currently no standardised molecular markers that assist in determining HNC prognosis. The literature for this systematic review and meta-analysis were sourced from multiple bibliographic databases. This review followed PRISMA guidelines. The Hazard Ratio (HR) was selected as the effect size metric to independently assess overall survival (OS), disease-free survival (DFS), and prognosis. Subgroup analysis was performed for individual highly represented miRNA. A total of 6843 patients across 50 studies were included in the systematic review and 34 studies were included in the meta-analysis. Studies across 12 countries were assessed, with China representing 36.7% of all included studies. The analysis of the survival endpoints of OS and DFS were conducted separately, with the overall pooled effect size (HR) for each being 1.825 (95% CI 1.527–2.181; p < 0.05) and 2.596 (95% CI 1.917–3.515; p < 0.05), respectively. Subgroup analysis was conducted for impact of miR-21, 200b, 155, 18a, 34c-5p, 125b, 20a and 375 on OS, and miR-21 and 34a on DFS. The pooled results were found to be statistically significant for both OS and DFS. The meta-analysis indicated that miRNA alterations can account for an 82.5% decrease in OS probability and a 159.6% decrease in DFS probability. These results indicate that miRNAs have potential clinical value as prognostic biomarkers in HNC, with miR-21, 125b, 34c-5p and 18a, in particular, showing great potential as prognostic molecular markers. Further large scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.

31 citations

Journal ArticleDOI
08 Feb 2019-PLOS ONE
TL;DR: It is noted that the combined effect estimate of HR across multiple studies indicated that increased miRNA expression in NPC potentially leads to poor overall survival, but further large-scale prospective studies on the clinical significance of the miRNAs, with sizable cohorts are necessary in order to obtain conclusive results.
Abstract: BACKGROUND: Nasopharyngeal cancer (NPC), despite being one of the most malignant head and neck carcinomas (HNC), lacks comprehensive prognostic biomarkers that predict patient survival. Therefore, this systematic review and meta-analysis is aimed to evaluate the potential prognostic value of miRNAs as prognostic biomarkers in NPC. METHODS: PRISMA guidelines were used to conduct this systematic review and meta-analysis study. Permutations of multiple "search key-words" were used for the search strategy, which was limited to articles published between January 2012 and March 2018. The retrieved articles were meticulously searched with multi-level screening by two reviewers and confirmed by other reviewers. Meta-analysis was performed using Hazard Ratios (HR) and associated 95% Confidence Interval (CI) of survival obtained from previously published studies. Publication bias was assessed by Egger's bias indicator test and funnel plot symmetry. RESULTS: A total of 5069 patients across 21 studies were considered eligible for inclusion in the systematic review, with 65 miRNAs being evaluated in the subsequent meta-analysis. Most articles included in this study originated from China and one study from North Africa. The forest plot was generated using cumulated survival data, resulting in a pooled HR value of 1.196 (95% CI: 0.893-1.601) indicating that the upregulated miRNAs increased the likelihood of death of NPC patients by 19%. CONCLUSION: To our knowledge, this is the first meta-analysis that examines the prognostic effectiveness of miRNAs as biomarkers in NPC patients. We noted that the combined effect estimate of HR across multiple studies indicated that increased miRNA expression in NPC potentially leads to poor overall survival. However, further large-scale prospective studies on the clinical significance of the miRNAs, with sizable cohorts are necessary in order to obtain conclusive results.

30 citations

Journal ArticleDOI
27 Jun 2019-Cancers
TL;DR: The results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients and further studies are needed to discover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in Pancic cancer.
Abstract: Background: pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients. Methods: the systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified. Findings: of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2–2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195–3.556; p-value: 0.09. Interpretation: our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to discover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.

24 citations


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Journal ArticleDOI
TL;DR: New perspectives for enhancing the efficacy of gemcitabine are outlined after reviewing the related factors of gem citabine metabolism, mechanism of action, and chemoresistance.
Abstract: Pancreatic ductal adenocarcinoma (PDAC), generally known as pancreatic cancer (PC), ranks the fourth leading cause of cancer-related deaths in the western world. While the incidence of pancreatic cancer is displaying a rising tendency every year, the mortality rate has not decreased significantly because of late diagnosis, early metastasis, and limited reaction to chemotherapy or radiotherapy. Adjuvant chemotherapy after surgical resection is typically the preferred option to treat early pancreatic cancer. Although 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel can profoundly improve the prognosis of advanced pancreatic cancer, the development of chemoresistance still leads to poor clinical outcomes. Chemoresistance is multifactorial as a result of the interaction among pancreatic cancer cells, cancer stem cells, and the tumor microenvironment. Nevertheless, more pancreatic cancer patients will benefit from precision treatment and targeted drugs. Therefore, we outline new perspectives for enhancing the efficacy of gemcitabine after reviewing the related factors of gemcitabine metabolism, mechanism of action, and chemoresistance.

271 citations

Journal ArticleDOI
TL;DR: It is indicated that NLR may be a helpful prognostic biomarker of patients with sepsis and that higher NLR values may indicate unfavorable prognoses in these patients.
Abstract: Background Neutrophil-to-lymphocyte ratio (NLR) has been used to predict the prognosis of patients with sepsis with inconsistent results. This meta-analysis aimed to clarify the prognostic value of NLR in patients with sepsis. Methods A comprehensive literature search for relevant studies, published prior to March 2019, was conducted using PubMed, Web of Science, and the China National Knowledge. Infrastructure database. Standard mean differences (SMDs) with 95% confidence intervals (CI) were used to evaluate the NLR of patients with sepsis retrospectively. Hazard ratios (HRs) with 95% CIs were used to evaluate the prognostic value of NLR in patients with sepsis. Results Patients from 14 studies (n = 11,564) were selected for evaluation. Nine studies (1371 patients) analyzed the NLR in these patients. The pooled results showed significantly higher NLR in non-survivors than in survivors (random-effects model: SMD = 1.18, 95% CI; 0.42–1.94). Nine studies (10,685 patients) evaluated the prognostic value of NLR for sepsis; the pooled results showed that higher NLR was associated with poor prognosis in patients with sepsis (fixed-effects model: HR = 1.75, 95% CI; 1.56–1.97). Subgroup analysis revealed that study design, cut-off NLR, or primary outcome did not affect the prognostic value of NLR in patients with sepsis. Conclusion This meta-analysis indicates that NLR may be a helpful prognostic biomarker of patients with sepsis and that higher NLR values may indicate unfavorable prognoses in these patients.

188 citations

Journal ArticleDOI
TL;DR: CT quantification of pneumonia lesions can early and non-invasively predict the progression to severe illness, providing a promising prognostic indicator for clinical management of COVID-19.
Abstract: Rationale: Some patients with coronavirus disease 2019 (COVID-19) rapidly develop respiratory failure or even die, underscoring the need for early identification of patients at elevated risk of severe illness. This study aims to quantify pneumonia lesions by computed tomography (CT) in the early days to predict progression to severe illness in a cohort of COVID-19 patients. Methods: This retrospective cohort study included confirmed COVID-19 patients. Three quantitative CT features of pneumonia lesions were automatically calculated using artificial intelligence algorithms, representing the percentages of ground-glass opacity volume (PGV), semi-consolidation volume (PSV), and consolidation volume (PCV) in both lungs. CT features, acute physiology and chronic health evaluation II (APACHE-II) score, neutrophil-to-lymphocyte ratio (NLR), and d-dimer, on day 0 (hospital admission) and day 4, were collected to predict the occurrence of severe illness within a 28-day follow-up using both logistic regression and Cox proportional hazard models. Results: We included 134 patients, of whom 19 (14.2%) developed any severe illness. CT features on day 0 and day 4, as well as their changes from day 0 to day 4, showed predictive capability. Changes in CT features from day 0 to day 4 performed the best in the prediction (area under the receiver operating characteristic curve = 0.93, 95% confidence interval [CI] 0.87~0.99; C-index=0.88, 95% CI 0.81~0.95). The hazard ratios of PGV and PCV were 1.39 (95% CI 1.05~1.84, P=0.023) and 1.67 (95% CI 1.17~2.38, P=0.005), respectively. CT features, adjusted for age and gender, on day 4 and in terms of changes from day 0 to day 4 outperformed APACHE-II, NLR, and d-dimer. Conclusions: CT quantification of pneumonia lesions can early and non-invasively predict the progression to severe illness, providing a promising prognostic indicator for clinical management of COVID-19.

161 citations

Journal ArticleDOI
TL;DR: This review provides a comprehensive overview of circulating miRNA analysis and highlights the importance of sampling and quality control, the technical aspects of miRNA extraction and quantification, recommendations for downstream analysis and conclude with future perspectives.

86 citations

Journal ArticleDOI
TL;DR: The underlying associations between exosomes and drug resistance of BC are summarized and exosome is proposed as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistant BC.
Abstract: Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention. The functional proteins or non-coding RNAs contained in exosomes secreted from tumor and stromal cells mediate drug resistance by regulating drug efflux and metabolism, pro-survival signaling, epithelial–mesenchymal transition, stem-like property, and tumor microenvironmental remodeling. In this review, we summarize the underlying associations between exosomes and drug resistance of BC and discuss the unique biogenesis of exosomes, the change of exosome cargo, and the pattern of release by BC cells in response to drug treatment. Moreover, we propose exosome as a candidate biomarker in predicting and monitoring the therapeutic drug response of BC and as a potential target or carrier to reverse the drug resistance of BC.

84 citations