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A comprehensive analysis for associations between multiple microRNAs and prognosis of osteosarcoma patients.

ABSTRACT: Background:Osteosarcoma (OS) is the most common malignant primary bone tumor occurring in children and young adults, which occupies the second important cause of tumor-associated deaths among children and young adults. Recent studies have demonstrated that many microRNAs (miRNAs) have abnormal expression in OS, and can function as prognostic factors of OS patients. However, no previous studies have comprehensively analyzed the relationship between multiple miRNAs and prognosis of OS patients. Methods:A total of 63 OS patients were retrospectively enrolled. The clinical characteristics were collected, and the expression levels of miRNA-21, miRNA-30c, miRNA-34a, miRNA-101, miRNA-133a, miRNA-214, miRNA-218, miRNA-433 and miRNA-539 in tumor tissues were measured through quantitative real-time polymerasechain reaction. Kaplan-Meier analysis was used to perform univariate survival analysis, and Cox regression model was used to perform multivariate survival analysis which included the variables with P < 0.1 in univariate survival analysis. Results:The cumulative survival for 1, 2 and 5 years was 90.48%, 68.25% and 38.10%, respectively, and mean survival time was (45.39 ± 3.60) months (95% CI [38.34-52.45]). Kaplan-Meier analysis demonstrated that TNM stage, metastasis or recurrence, miRNA-21, miRNA-214, miRNA-34a, miRNA-133a and miRNA-539 were correlated with cum survival, but gender, age, tumor diameter, differentiation, miRNA-30c, miRNA-433, miRNA-101 and miRNA-218 were not. Multivariate survival analysis demonstrated that miRNA-21 (hazard ratio (HR): 3.457, 95% CI [2.165-11.518]), miRNA (HR: 3.138, 95% CI [2.014-10.259]), miRNA-34a (HR: 0.452, 95% CI [0.202-0.915]), miRNA-133a (HR: 0.307, 95% CI [0.113-0.874]) and miRNA-539 (HR: 0.358, 95% CI [0.155-0.896]) were independent prognostic markers of OS patients after adjusting for TNM stage (HR: 2.893, 95% CI [1.496-8.125]), metastasis or recurrence (HR: 3.628, 95% CI [2.217-12.316]) and miRNA-30c (HR: 0.689, 95% CI [0.445-1.828]). Conclusions:High expression of miRNA-21 and miRNA-214 and low expression of miRNA-34a, miRNA-133a and miRNA-539 were associated with poor prognosis of OS patients after adjusting for TNM stage, metastasis or recurrence and miRNA-30c.

SUBMITTER: Yang W

PROVIDER: S-EPMC6977468 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A comprehensive analysis for associations between multiple microRNAs and prognosis of osteosarcoma patients.

Yang Wen W Qi Yu-Bin YB Si Meng M Hou Yong Y Nie Lin L

PeerJ 20200120

<h4>Background</h4>Osteosarcoma (OS) is the most common malignant primary bone tumor occurring in children and young adults, which occupies the second important cause of tumor-associated deaths among children and young adults. Recent studies have demonstrated that many microRNAs (miRNAs) have abnormal expression in OS, and can function as prognostic factors of OS patients. However, no previous studies have comprehensively analyzed the relationship between multiple miRNAs and prognosis of OS pati ...[more]

PMID: 31998559

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Project description:Osteosarcoma is a highly malignant bone cancer which primarily occurs in children and young adults. Increasing evidence indicates that long noncoding RNAs (lncRNAs), which function as competing endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) and messenger RNAs (mRNAs), play a pivotal role in the pathogenesis and progression of cancers. The regulatory mechanisms of lncRNA-mediated ceRNAs in osteosarcoma have not been fully elucidated. In this study, we identified differentially expressed lncRNAs, miRNAs, and mRNAs in osteosarcoma based on RNA microarray profiles in the Gene Expression Omnibus (GEO) database. A ceRNA network was constructed utilizing bioinformatic tools. Kaplan-Meier survival analysis showed that lncR-C3orf35 and HMGB1 were associated with poor prognosis of osteosarcoma patients. Furthermore, results of Gene Set Enrichment Analysis (GSEA) suggested that lncR-C3orf35 may be involved in cellular invasion, the Toll-like receptor signaling pathway, and immune cell infiltration in the tumor microenvironment. Further analysis showed that patients with osteosarcoma metastasis expressed higher levels of lncR-C3orf35 and HMGB1 compared to metastasis-free patients. Moreover, the metastasis-free survival rate of the high lncR-C3orf35/HMGB1 expression group was significantly lower than that of the low expression group. The ESTIMATE algorithm was used to calculate the immune score and stromal scores for each sample. High lncR-C3orf35 and HMGB1 levels were correlated with low immune scores. ImmuCellAI analysis revealed that a low proportion of macrophage infiltration was associated with high lncR-C3orf35 and HMGB1 expression. The differential expression of lncR-C3orf35, miR-142-3p, and HMGB1 was further verified by quantitative real-time PCR. This study indicates that lncR-C3orf35 could be considered as a novel potential biomarker and therapeutic target of osteosarcoma, which may contribute to a better understanding of ceRNA regulatory mechanisms.

Project description:The aim of this study was to assess and analyze the nutritional status (NS) and immune status of pancreatic cancer (PC) patients. The retrospective analysis included 80 PC patients undergoing curative pancreatic resection in the Department of Digestive Tract Surgery of the Medical University (Katowice, Poland). Patients were divided by the tumor location (proximal vs. distal), age (≤65 years vs. >65 years), Nutritional Risk Score 2002 (NRS 2002) (<3 vs. ≥3), prognostic nutritional index (PNI) (<45 vs. ≥45), and the presence of postoperative complications (no-complication vs. complication) as well as the use of neoadjuvant chemotherapy (no neoadjuvant chemotherapy vs. neoadjuvant chemotherapy) into two subgroups, which were compared. Significantly higher weight loss was related to the proximal tumor location (p = 0.0104). Significantly lower serum total protein (p = 0.0447), albumin (p = 0.0468), hemoglobin (p = 0.0265) levels, and PNI (p = 0.03) were reported in older patients. The higher nutritional risk according to NRS 2002 was significantly associated with higher age (p = 0.0187), higher weight loss (p < 0.01), lower body mass index (BMI) (p = 0.0293), lower total lymphocyte count (p = 0.0292), longer duration of hospitalization (p = 0.020), neoadjuvant chemotherapy (p < 0.01), and preoperative biliary drainage (p = 0.0492). The lower PNI was significantly associated with higher weight loss (p = 0.0407), lower serum total protein and albumin concentration, lymphocyte count (p < 0.01) and higher neutrophil/lymphocyte (NLR), monocyte/lymphocyte (MLR), platelet/lymphocyte (PLR) ratios, and duration of hospitalization (p < 0.01). In the multiple logistic regression analysis, BMI ≥ 30 kg/m2 (OR: 8.62; 95% CI: 1.24-60.04; p = 0.029521) and NRS 2002 ≥ 3 (OR: 2.87; 95% CI: 0.88-9.33; p = 0.048818) predicted postoperative complications. In the multiple linear regression analysis, the higher NRS 2002 score was linked with the longer duration of hospitalization (b = 7.67948; p = 0.043816), and longer duration of postoperative hospitalization was associated with a higher complication rate (b = 0.273183; p = 0.003100). Nutritional impairment correlates with a systemic inflammatory response in PC patients. Obesity (BMI ≥ 30 kg/m2) and malnutrition (NRS 2002 ≥ 3) predict postoperative complications, which are associate with a longer hospital stay. Assessment of nutritional and immune status using basic diagnostic tools and PNI and immune ratio (NLR, MLR, PLR) calculation should be the standard management of PC patients before surgery to improve the postoperative outcome.

Project description:BackgroundGlycolysis and cholesterol synthesis are crucial in cancer metabolic reprogramming. The aim of this study was to identify a glycolysis and cholesterol synthesis-related genes (GCSRGs) signature for effective prognostic assessments of osteosarcoma patients.MethodsGene expression data and clinical information were obtained from GSE21257 and TARGET-OS datasets. Consistent clustering method was used to identify the GCSRGs-related subtypes. Univariate Cox regression and LASSO Cox regression analyses were used to construct the GCSRGs signature. The ssGSEA method was used to analyze the differences in immune cells infiltration. The pRRophetic R package was utilized to assess the drug sensitivity of different groups. Western blotting, cell viability assay, scratch assay and Transwell assay were used to perform cytological validation.ResultsThrough bioinformatics analysis, patients diagnosed with osteosarcoma were classified into one of 4 subtypes (quiescent, glycolysis, cholesterol, and mixed subtypes), which differed significantly in terms of prognosis and tumor microenvironment. Weighted gene co-expression network analysis revealed that the modules strongly correlated with glycolysis and cholesterol synthesis were the midnight blue and the yellow modules, respectively. Both univariate and LASSO Cox regression analyses were conducted on screened module genes to identify 5 GCSRGs (RPS28, MCAM, EN1, TRAM2, and VEGFA) constituting a prognostic signature for osteosarcoma patients. The signature was an effective prognostic predictor, independent of clinical characteristics, as verified further via Kaplan-Meier analysis, ROC curve analysis, univariate and multivariate Cox regression analysis. Additionally, GCSRGs signature had strong correlation with drug sensitivity, immune checkpoints and immune cells infiltration. In cytological experiments, we selected TRAM2 as a representative gene to validate the validity of GCSRGs signature, which found that TRAM2 promoted the progression of osteosarcoma cells. Finally, at the pan-cancer level, TRAM2 had been correlated with overall survival, progression free survival, disease specific survival, tumor mutational burden, microsatellite instability, immune checkpoints and immune cells infiltration.ConclusionTherefore, we constructed a GCSRGs signature that efficiently predicted osteosarcoma patient prognosis and guided therapy.

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A comprehensive analysis for associations between multiple microRNAs and prognosis of osteosarcoma patients.

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A comprehensive analysis for associations between multiple microRNAs and prognosis of osteosarcoma patients.

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