-
Non-coding RNA Research Jun 2024Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles... (Review)
Review
Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles published from January 2010 to September 2023 were searched across eight databases to compare circRNA expression profiles in osteosarcoma and control samples (human, animal and cell lines). Meta-analysis was conducted under a random effects model. Subgroup analysis of circRNAs in different samples and tissues was performed. Diagnostic value was evaluated using receiver operator characteristic curves. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis explored functions of circRNA host genes. A circRNA-miRNA-mRNA axis depicted the regulatory mechanism in osteosarcoma. Among 1356 circRNAs with differential expression were identified across 226 original studies, only 74 were reported in at least three published sub-studies. Meta-analysis identified 58 dysregulated circRNAs (52 upregulated and 6 downregulated). Eleven circRNAs consistently showed dysregulation in tissues and cell lines, with hsa_circ_0005721 showing potential as a circulating biomarker in osteosarcoma. Sensitivity analysis demonstrated 97 % consistency. The overall area under the curve was 0.87 (95 % CI, 0.83-0.89). GO and KEGG enrichment analyses revealed host gene involvement in cancer. The circRNA-miRNA-mRNA axis revealed the regulatory axis and interactions within osteosarcoma specifically. This study demonstrates circRNAs as potential diagnostic biomarkers for osteosarcoma. Consistently reported dysregulated circRNAs are potential biomarkers in osteosarcoma pathogenesis, with hsa_circ_0005721 as a potential circulating biomarker for diagnosis and treatment.
PubMed: 38505307
DOI: 10.1016/j.ncrna.2024.01.007 -
International Journal of Molecular... Nov 2014Epithelial-to-mesenchymal transition (EMT) facilitates tumor metastasis. Twist is a basic helix-loop-helix protein that modulates many target genes through... (Meta-Analysis)
Meta-Analysis Review
Epithelial-to-mesenchymal transition (EMT) facilitates tumor metastasis. Twist is a basic helix-loop-helix protein that modulates many target genes through E-box-responsive elements. There are two twist-like proteins, Twist-1 and Twist-2, sharing high structural homology in mammals. Twist-1 was found to be a key factor in the promotion of metastasis of cancer cells, and is known to induce EMT. Twist-1 participation in carcinoma progression and metastasis has been reported in a variety of tumors. However, controversy exists concerning the correlation between Twist-1 and prognostic value with respect to carcinoma. A systematic review and meta-analysis were performed to determine whether the expression of Twist-1 was associated with the prognosis of carcinoma patients. This analysis included 17 studies: four studies evaluated lung cancer, three evaluated head and neck cancer, two evaluated breast cancer, two evaluated esophageal cancer, two evaluated liver cancer and one each evaluated osteosarcoma, bladder, cervical and ovarian cancer. A total of 2006 patients were enrolled in these studies, and the median trial sample size was 118 patients. Twist-1 expression was associated with worse overall survival (OS) at both 3 years (hazard ratio "HR" for death = 2.13, 95% CI = 1.86 to 2.45, p < 0.001) and 5 years (HR for death = 2.01, 95% CI = 1.76 to 2.29, p < 0.001). Expression of Twist-1 is associated with worse survival in carcinoma.
Topics: Gene Expression Regulation, Neoplastic; Genetic Heterogeneity; Humans; Neoplasms; Nuclear Proteins; Prognosis; Publication Bias; Survival Analysis; Twist-Related Protein 1; Up-Regulation
PubMed: 25429425
DOI: 10.3390/ijms151221621 -
International Journal of Surgery... Dec 2016There are conflicting findings about the effect of resection margins on local recurrence in osteosarcoma after surgery. In this meta-analysis, we examined the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
There are conflicting findings about the effect of resection margins on local recurrence in osteosarcoma after surgery. In this meta-analysis, we examined the association between local recurrence and resection margins for osteosarcoma in extremity and pelvis.
METHODS
EMBASE, PubMed and Cochrane CENTRAL were searched from January 1980 to July 2016. The quality of included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale. The odds ratio and 95% confidence interval of local recurrence were estimated, respectively, for inadequate vs adequate margins and marginal vs wide margins using a random-effect model. Chi-square test was performed to comparing the local recurrence rate between extremity and pelvic osteosarcomas with an identical surgical margin.
RESULTS
Thirteen articles involving 1559 patients (175 with and 1384 without local recurrence) were included in this study. The meta-analysis showed that the osteosarcoma resected with inadequate and marginal margins, whether in extremity or in pelvis, were associated with a significantly higher local recurrence rate than the osteosarcoma resected with adequate and wide margins, respectively. Chi-square test showed that, when pelvic and extremity osteosarcomas were removed with an identical resection margin, the local recurrence was significantly more frequent in pelvis osteosarcoma than in extremity osteosarcoma.
CONCLUSION
This study provides level IIa evidence to support that the surgery with adequate or wide resection margin has positive effect on reducing the risk of local recurrence in osteosarcoma. In addition, the factors independent of resection margin are more likely to increase the risk of local recurrence in pelvic osteosarcoma.
LEVEL OF EVIDENCE
Level IIa, Therapeutic study.
Topics: Bone Neoplasms; Extremities; Humans; Margins of Excision; Neoplasm Recurrence, Local; Osteosarcoma; Pelvic Bones
PubMed: 27840310
DOI: 10.1016/j.ijsu.2016.11.016 -
Annals of Joint 2023Osteosarcoma (OS) and chondrosarcoma (CS) are primary bone malignancies whose prognoses have stagnated despite advancements in surgical management, chemotherapy,... (Review)
Review
BACKGROUND
Osteosarcoma (OS) and chondrosarcoma (CS) are primary bone malignancies whose prognoses have stagnated despite advancements in surgical management, chemotherapy, radiation therapy, and immunotherapy. The role of the immune system in generating anti-cancer physiologic responses is critical to prognosis. Prior studies have explored if immune system activation via infection enhances survival in bone sarcomas without a clear consensus.
METHODS
This study sought to (I) retrospectively examine the effect of postoperative infection on survival in OS and CS and (II) systematically review the effect of postoperative infection on survival in primary bone malignancies. We performed a retrospective case-control study of 192 patients treated between 1/2000-12/2015 at a single academic sarcoma referral center. Patients with OS or CS undergoing operative resection were included. Eligible patients were grouped by presence of metastasis, and survival was compared between patients with or without postoperative infection. Furthermore, we performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines investigating the effect of infection on primary bone malignancy survival. Risk of bias assessment was performed utilizing the ROBINS-I (Risk of Bias in Non-randomized Studies-of Interventions) assessment tool. All presented studies included author information, study population, and overall or disease-free survival results.
RESULTS
One hundred and four patients were included, with 85 without infection (26 metastatic, 59 non-metastatic) and 19 with infection (10 metastatic, 9 non-metastatic). Five-year survival was greatest in patients without metastasis with a postoperative infection (100%), followed by patients without metastasis who were infection-free (80%). Five-year survival was comparatively lower in patients with metastasis who were infection-free (35%) and lowest in patients with metastasis with a postoperative infection (20%). No significant differences were present (P=0.17) on log-rank analysis. Our systematic review collected six studies exploring the impact of infection on primary bone malignancy survival, with two studies reporting significant findings of infection improving survival. Limitations of this review included risk of bias due to confounding, inconsistency comparing outcomes, and differences in patient populations.
CONCLUSIONS
This retrospective study and systematic review suggests postoperative infection may play a role in modulating immune response to malignancy. Understanding the synergy between anti-pathogen and anti-cancer responses warrants further investigation as an alternative method of targeted cancer treatment.
PubMed: 38529233
DOI: 10.21037/aoj-22-41 -
Journal of Orthopaedic Surgery and... Dec 2021In recent years, numerous investigations have been conducted to determine the clinical significance and critical functions of vascular endothelial growth factor (VEGF)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In recent years, numerous investigations have been conducted to determine the clinical significance and critical functions of vascular endothelial growth factor (VEGF) in various malignant cancers. The purpose of this meta-analysis was to comprehensively evaluate the prognostic and clinicopathological value of VEGF in patients with osteosarcoma.
METHODS
We performed a systematic literature retrieval of available databases. Odds ratios (ORs) or standard mean difference (SMD) for clinicopathological parameters, hazard ratios (HRs) for overall survival and disease-free survival were calculated to assess the correlation between VEGF expression and prognosis in patients with osteosarcoma.
RESULTS
A total of 22 studies with 1144 patients were included in our study. Pooled analyses showed that VEGF overexpression predicted worse overall survival (HR, 2.42; 95% CI, 1.87-3.11, p < 0.001) and disease-free survival (HR, 2.604; 95% CI, 1.698-3.995, p < 0.001), respectively. Furthermore, investigation regarding osteosarcoma clinicopathologic characteristics suggested that high VEGF expression was significantly associated with metastasis (OR, 4.39; 95% CI, 2.77-6.95; p < 0.001), clinical stage (OR, 0.73; 95% CI, 0.62-0.87; p < 0.001), and microvessel density (SMD, 3.33, 95% CI,1.57-5.10, p < 0.001), but not associated with tumor location, gender, age, local recurrence, and chemotherapy response.
CONCLUSION
Our meta-analysis findings suggest that elevated VEGF expression may be a predictive biomarker for poor prognosis and adverse clinicopathological characteristics in patients with osteosarcoma.
Topics: Biomarkers, Tumor; Bone Neoplasms; Endothelial Growth Factors; Humans; Osteosarcoma; Prognosis; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 34963495
DOI: 10.1186/s13018-021-02888-3 -
Pediatric Blood & Cancer Sep 2015Pediatric, adolescent, and young adult survivors of bone sarcomas are at risk for poor quality of life (QOL). We conducted a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pediatric, adolescent, and young adult survivors of bone sarcomas are at risk for poor quality of life (QOL). We conducted a systematic review and meta-analysis to summarize the literature describing QOL in this population and differences in QOL based on local control procedures.
PROCEDURE
Included studies described ≥5 patients <25 years old who had completed local control treatment for bone sarcoma, defined QOL as a main outcome, and measured it with a validated instrument. Data extraction and quality assessments were conducted with standardized tools. Meta-analyses compared QOL based on surgical procedure (limb-sparing vs. amputation) and were stratified by assessment type (objective physical function, clinician-assessed disability, patient-reported disability, and patient-reported QOL). Effect sizes were reported as the standard mean difference when multiple instruments were used within a comparison and weighted mean difference otherwise. All were weighted by inverse variance and modeled with random effects.
RESULTS
Twenty-two of 452 unique manuscripts were included in qualitative syntheses, eight of which were included in meta-analyses. Manuscripts were heterogeneous with respect to included patient populations (age, tumor type, time since treatment) and QOL instruments. Prospective studies suggested that QOL improves over time, and that female sex and older age at diagnosis are associated with poor QOL. Meta-analyses showed no differences in outcomes between patients who underwent limb-sparing versus amputation for local control.
CONCLUSION
QOL studies among children and AYAs with bone sarcoma are remarkably diverse, making it difficult to detect trends in patient outcomes. Future research should focus on standardized QOL instruments and interpretations.
Topics: Adolescent; Age Factors; Amputation, Surgical; Bone Neoplasms; Child; Child, Preschool; Cross-Sectional Studies; Disabled Persons; Female; Humans; Limb Salvage; Male; Prospective Studies; Quality of Life; Recovery of Function; Sarcoma; Self Report; Surveys and Questionnaires; Survivors; Young Adult
PubMed: 25820683
DOI: 10.1002/pbc.25514 -
Advances in Therapy Jan 2021As a result of the increased use of radiotherapy (RT) and improved long-term overall survival of patients with cancers of the head and neck (HN), the frequency of... (Review)
Review
INTRODUCTION
As a result of the increased use of radiotherapy (RT) and improved long-term overall survival of patients with cancers of the head and neck (HN), the frequency of radiation-induced sarcomas of the head and neck (RISHN) may be increasing. The main objective of this systematic review was to determine the existing evidence on the frequency, treatment, and outcome of RISHN.
METHODS
Using PRISMA guidelines we conducted a systematic review of the literature published from 2000 to 2020.
RESULTS
Our review includes data of 560 patients from 64 articles. The total frequency of RISHNs among the reviewed series was 0.15%. The most frequent location of the primary tumor treated by RT was the nasopharynx. The mean RT dose used was 62 Gy, mean latency interval between irradiation and occurrence of RISHN was 11.1 years, and the most common RISHN location was the sinonasal region. Osteosarcoma was the principal histology, followed by fibrosarcoma. Surgery was the most frequently applied treatment modality. Of all patients with RISHN, 40.7% died of this disease after a mean interval of 13.9 months.
CONCLUSIONS
Notwithstanding the increased use of RT, the number of reported RISHNs has not increased substantially during the past two decades. Surgery with wide margins forms the best therapeutic option for these cases, but the outcome remains poor.
Topics: Bone Neoplasms; Head and Neck Neoplasms; Humans; Osteosarcoma; Retrospective Studies; Sarcoma
PubMed: 33184778
DOI: 10.1007/s12325-020-01556-y -
The Bone & Joint Journal Oct 2014Opinion remains divided as to whether the development of pathological fracture affects the prognosis of patients with an osteosarcoma of the extremities. We conducted a... (Meta-Analysis)
Meta-Analysis Review
Opinion remains divided as to whether the development of pathological fracture affects the prognosis of patients with an osteosarcoma of the extremities. We conducted a comprehensive systematic review and meta-analysis of papers which reported the outcomes of osteosarcoma patients with and without a pathological fracture. There were eight eligible papers for final analysis which reported on 1713 patients, of whom 303 (17.7%) had a pathological fracture. The mean age for 1464 patients in six studies was 23.2 years old (2 to 82). The mean follow-up for 1481 patients in seven studies was 90.1 months (6 to 240). The pooled estimates of local recurrence rates in osteosarcoma patients with and without pathological fractures were 14.4% (8.7 to 20.0) versus 11.4% (8.0 to 14.8). The pooled estimate of relative risk was 1.39 (0.89 to 2.20). The pooled estimates of five-year event-free survival rates in osteosarcoma patients with and without a pathological fracture were 49.3% (95% CI 43.6 to 54.9) versus 66.8% (95% CI 60.7 to 72.8). The pooled estimate of relative risk was 1.33 (1.12 to 1.59). There was no significant difference in the rate of local recurrence between patients who were treated by amputation or limb salvage. The development of a pathological fracture is a negative prognostic indicator in osteosarcoma and is associated with a reduced five-year event-free survival and a possibly higher rate of local recurrence. Our findings suggest that there is no absolute indication for amputation, as similar rates of local recurrence can be achieved in patients who are carefully selected for limb salvage.
Topics: Bone Neoplasms; Combined Modality Therapy; Fractures, Spontaneous; Global Health; Humans; Incidence; Osteosarcoma; Prognosis; Survival Rate
PubMed: 25274928
DOI: 10.1302/0301-620X.96B10.34370 -
Radiation Oncology (London, England) Oct 2022This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to systematically evaluate and conduct a meta-analysis of the efficacy and safety of carbon ion radiotherapy for bone sarcomas.
METHODS
We searched for articles using the PubMed, Embase, Cochrane Library, and the Web of Science databases from their inception to January 12, 2022. Two researchers independently screened the literature and extracted data based on the inclusion and exclusion criteria. Statistical analyses were performed using STATA version 14.0.
RESULTS
We searched for 4378 candidate articles, of which 12 studies were included in our study according to the inclusion and exclusion criteria. Of the 897 BSs patients who received carbon ion radiotherapy in the studies, 526 patients had chordoma, 255 patients had chondrosarcoma, 112 patients had osteosarcoma, and 4 patients had other sarcomas. The local control rate at 1, 2, 3, 4, 5, and 10 years in these studies were 98.5% (95% confidence interval [CI] = 0.961-1.009, I = 0%), 85.8% (95% CI = 0.687-1.030, I = 91%), 86% (95% CI = 0.763-0.957, I = 85.3%), 91.1% (95% CI = 0.849-0.974), 74.3% (95% CI = 0.666-0.820, I = 85.2%), and 64.7% (95% CI = 0.451-0.843, I = 95.3%), respectively. The overall survival rate at 1, 2, 3, 4, 5, and 10 years in these studies were 99.9% (95% CI = 0.995-1.004, I = 0%), 89.6% (95% CI = 0.811-0.980, I = 96.6%), 85% (95% CI = 0.750-0.950, I = 89.4%), 92.4% (95% CI = 0.866-0.982), 72.7% (95% CI = 0.609-0.844, I = 95.3%), and 72.1% (95% CI = 0.661-0.781, I = 46.5%), respectively. Across all studies, the incidence of acute and late toxicities was mainly grade 1 to grade 2, and grade 1 to grade 3, respectively.
CONCLUSION
As an advanced radiotherapy, carbon ion radiotherapy is promising for patients with bone sarcomas that are unresectable or residual after incomplete surgery. The data indicated that carbon ion radiotherapy was safe and effective for bone sarcomas, showing promising results for local control, overall survival, and lower acute and late toxicity.
PROSPERO REGISTRATION NUMBER
CRD42021258480.
Topics: Humans; Heavy Ion Radiotherapy; Osteosarcoma; Chondrosarcoma; Sarcoma; Bone Neoplasms
PubMed: 36284346
DOI: 10.1186/s13014-022-02089-0 -
Sarcoma 2020To investigate prognostic factors in pediatric and young adult patients with localized osteosarcoma that could predict the development of subsequent pulmonary metastases... (Review)
Review
AIM
To investigate prognostic factors in pediatric and young adult patients with localized osteosarcoma that could predict the development of subsequent pulmonary metastases and lead to an ability to risk-stratify therapy. We performed a systematic review of the literature published since January 1990 to establish common evidence-based prognostic factors.
METHODS
PubMed and Embase searches (Jan 1990-Aug 2018) were performed. Two reviewers independently selected papers for patients with localized osteosarcoma with subsequent metastatic development and then reviewed for quality of methods and prognostic factors.
RESULTS
Database searches yielded 216 unique results. After screening, 27 full-text articles were studied in depth, with 9 items fulfilling predetermined inclusion and exclusion criteria. Age, tumor location, tumor size/volume, and histologic response carried independent prognostic value in the majority of the studies.
CONCLUSIONS
Several prognostic factors seemed to be consistent amongst the studies, but the heterogeneity and smaller sizes of the study populations made pooling of results difficult. Standardization of larger patient populations and consistent definitions/cutoffs for prognostic factors are needed to further assess for consistent prognostic factors and potential predictive models to be developed.
PubMed: 32300279
DOI: 10.1155/2020/7431549