Advances in materials used for minimally invasive treatment of vertebral compression fractures.

Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and summarize the approaches for improving the characteristics of bone cement. Finally, we review the types and clinical efficacy of new vertebral implants. This review may provide valuable insights into newer strategies and methods for future research; it may also improve understanding on the application of minimally invasive materials for the treatment of vertebral compression fractures.

The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.

Osteosarcoma (OS) is one of the most aggressive bone tumors worldwide. Emerging documents have shown that long noncoding RNAs (lncRNAs) elicit crucial regulatory functions in the process of tumorigenesis. LncRNA DLGAP1-AS2 is recognized as a regulator in several types of cancers, but its biological functions and molecular mechanisms in OS remain to be elucidated. RT-qPCR and In situ hybridization (ISH) were used to evaluate DLGAP1-AS2 expression in OS samples. Western blotting was used for the measurement of the protein levels of hexokinase 2 (HK2) and epithelial-mesenchymal transition (EMT)-related markers. The proliferation of OS cells was determined using a CCK-8 assay and EdU assay. TUNEL assay and flow cytometry were performed to assess OS cell apoptosis. Glucose metabolism in vitro assays were used. The binding relations among miR-451a, HK2, and DLGAP1-AS2 were validated by luciferase reporter assay. The cellular distribution of DLGAP1-AS2 in OS cells was determined by FISH and subcellular fractionation assays. Mouse xenograft models were established to perform the experiments in vivo. We found that DLGAP1-AS2 expression was upregulated in OS tissues and cells. Downregulation of DLGAP1-AS2 expression suppressed the malignancy of OS cells by restraining cell proliferation, the EMT process, invasiveness, migration, and aerobic glycolysis and accelerating apoptotic behaviors. Of note, silenced DLGAP1-AS2 restrained tumor growth and metastasis in vivo. However, DLGAP1-AS2 overexpression accelerated the progression of OS. We further found that DLGAP1-AS2 upregulation was induced by hypoxia and low glucose. Additionally, DLGAP1-AS2 bound to miR-451a to upregulate HK2 expression. Rescue assays revealed that the DLGAP1-AS2/miR-451a/HK2 axis contributed to OS cell malignancy by promoting aerobic glucose metabolism. Overall, these findings revealed a new regulatory pathway where DLGAP1-AS2 upregulated HK2 expression by sponging miR-451a to accelerate OS development.

Circ_0001825 promotes osteogenic differentiation in human-derived mesenchymal stem cells via miR-1270/SMAD5 axis.

BACKGROUND: The implication of deregulated circular RNAs in osteoporosis (OP) has gradually been proposed. Herein, we aimed to study the function and mechanism of circ_0001825 in OP using osteogenic-induced human-derived mesenchymal stem cells (hMSCs). METHODS: The content of genes and proteins was tested by quantitative real-time polymerase chain reaction and Western blotting. The osteogenic differentiation in hMSCs were evaluated by ALP activity and Alizarin Red staining, as well as the detection of osteogenesis-related markers. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry. The binding between miR-1270 and circ_0001825 or SMAD5 (SMAD Family Member 5) was confirmed by using dual-luciferase reporter assay and pull-down assay. RESULTS: Circ_0001825 was lowly expressed in OP patients and osteogenic induced hMSCs. Knockdown of circ_0001825 suppressed hMSC viability and osteogenic differentiation, while circ_0001825 overexpression showed the exact opposite effects. Mechanistically, circ_0001825/miR-1270/SMAD5 formed a feedback loop. MiR-1270 was increased and SMAD5 was decreased in OP patients and osteogenic induced hMSCs. MiR-1270 up-regulation suppressed hMSC viability and osteogenic differentiation, which was reversed by SMAD5 overexpression. Moreover, miR-1270 deficiency abolished the effects of circ_0001825 knockdown on hMSCs. CONCLUSION: Circ_0001825 promoted hMSC viability and osteogenic differentiation via miR-1270/SMAD5 axis, suggesting the potential involvement of circ_0001825 in osteoporosis.

Role and Mechanism of circ_0058063/miR-635 Axis in the Malignant Phenotype of Multiple Myeloma RPMI8226 Cells.

OBJECTIVE: This study aims to explore circ_0058063 effect on multiple myeloma cells malignant phenotype and its feasible mechanism. METHODS: We selected 47 cases of multiple myeloma tissues and 47 cases of normal bone marrow tissues and then used RT-qPCR method to test circ_0058063 and miR-635 expression in the tissues. Myeloma cells RPMI8226 were transfected with si-circ_0058063, miR-635 mimic, and si-circ_0058063 + anti-miR-635, respectively. Then, we adopt CCK-8 method, flow cytometry method, and Transwell and western blot methods to detect the influences of knockdown of circ_0058063 or miR-635 overexpression on RPMI8226 cell proliferation, apoptosis, migration, and invasion and also Ki-67, Bax, Bcl-2, MMP-2, and MMP-9 protein expression. The dual luciferase reporter gene assay experiment proved that it has regulatory relationship between circ_0058063 and miR-635. RESULTS: circ_0058063 expression of multiple myeloma was higher than that in normal bone marrow tissue (P < 0.05), while miR-635 expression was lower than that in normal bone marrow tissue (P < 0.05). Knockdown of circ_0058063 or overexpression of miR-635 could reduce proliferation capacity, migration, invasion cell quantities, and Ki-67, MMP-2, MMP-9, and Bcl-2 protein expression (P < 0.05), while increasing apoptosis rate together with Bax protein expression (P < 0.05). circ_0058063 targets to negatively regulate miR-635, while knocking down miR-635 reverses the influences of knocking down circ_0058063 on RPMI8226 proliferation, apoptosis, migration, and invasion. CONCLUSION: circ_0058063 expression increased in multiple myeloma tissues. Knocking down its expression may inhibit myeloma proliferation, migration, and invasion by targeting and upregulating miR-635 and also promote cell apoptosis. As for multiple myeloma treatment, circ_0058063/miR-635 may provide new molecular targets.

LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-ß/SMAD Signaling Pathway and Upregulating SSH2 Expression.

Osteosarcoma (OS), a frequent malignant tumor which mainly occurs in the bone. The roles of long noncoding RNAs (lncRNAs) have been revealed in cancers, including OS. LncRNA long intergenic non-protein coding RNA (LINC00174) has been validated as an oncogene in several cancers. However, the role of LINC00174 in OS has not been explored. In our research, loss-of-function assays were conducted to explore the function of LINC00174 in OS cells. Then, we explored the downstream pathway of LINC00174 in OS cells. Bioinformatics, RNA pull-down and RIP experiments investigated the downstream mechanism of LINC00174 in OS cells. Finally, in vivo assays clarified the effect of LINC00174 on tumorigenesis. We found that LINC00174 was upregulated in OS tissues and cells. LINC00174 knockdown repressed OS cell growth. Mechanistically, LINC00174 knockdown suppressed the TGF-ß/SMAD pathway. LINC00174 interacted with miR-378a-3p, and slingshot protein phosphatase 2 (SSH2) 3'UTR was targeted by miR-378a-3p in OS cells. Rescue assays showed that SSH2 upregulation or miR-378a-3p inhibition counteracted the inhibitory effect of LINC00174 depletion in OS cell growth. Additionally, LINC00174 depletion suppressed tumor growth in mice. In conclusion, LINC00174 promotes OS cellular malignancy and tumorigenesis via the miR-378a-3p/SSH2 axis and the TGF-ß/SMAD pathway, which might provide a novel insight for OS treatment.

Aberrantly DNA Methylated-Differentially Expressed Genes in Pancreatic Cancer Through an Integrated Bioinformatics Approach.

Pancreatic cancer remains one of the chief contributors to cancer related deaths on a global scale, with its diagnosis often associated with poor prognosis and high mortality. Accumulating literature continues to highlight the role of aberrant DNA methylation in relation to pancreatic cancer progression. Integrated bioinformatics approaches in the characterization of methylated-differentially expressed genes (MeDEGs) in pancreatic cancer were employed to enhance our understanding of the potential underlying molecular mechanisms of this cancer. We initially identified differentially expressed genes (DEGs) between 178 pancreatic cancer samples and 4 normal samples and differentially methylated genes (DMGs) based on 185 pancreatic cancer samples as well as 10 normal samples by analyzing RNA sequencing data in the TCGA database. Eventually, 31 MeDEGs including 5 hypomethylated/upregulated genes and 26 hypermethylated/downregulated genes were identified. Univariate Cox model and Kaplan-Meier method revealed that, among 31 MeDEGs, 5 hypermethylated/downregulated genes (ZNF804A, ZFP82, TRIM58, SOX17, and C12orf42) were correlated with poor survival of patients with pancreatic cancer. KEGG pathway enrichment analysis by GSEA 3.0 and the protein-protein interaction (PPI) network revealed that these 5 MeDEGs were enriched in numerous cancer-related pathways in addition to interacting with each other, highlighting a significant role in the development of pancreatic cancer. Taken together, the key findings of the current study demonstrate that ZNF804A, ZFP82, TRIM58, SOX17, and C12orf42 are hypermethylated/downregulated genes in pancreatic cancer and may be associated, through their modulation of specific pathways, with unfavorable pancreatic cancer prognosis.

Cloacal malformation: A rare case report and review of prenatal imagings.

RATIONALE: Cloacal malformation (CM) is a serious type of anorectal and urogenital tract malformation. However, prenatal ultrasound (US) detection of CM is challenging. In this paper, we reported a rare case of CM prenatally diagnosed by US and magnetic resonance imaging (MRI), as well as reviewed the prenatal US and MRI characteristics of CM in the literature. PATIENT CONCERNS: A 30-year-old pregnant woman complained of cystic mass in the fetal abdomen detected by prenatal US. DIAGNOSIS: Fetus CM. INTERVENTIONS: The fetus was diagnosed as fetal CM by US and MRI, then the pregnant woman received a drug-induced labor treatment. After the neonate was delivered, the measurement was performed on the weight, length, head circumference, abdomen circumference, and bilateral thigh circumference. OUTCOMES: A female dead neonate was delivered from the vagina of the gravida, showing congenital anus absence. Prenatal ultrasound demonstrated right kidney duplication, hydronephrosis, and right ureteral dilatation. Meanwhile, prenatal MRI showed a cystic cavity, double collecting systems of right kidney, right ureteral dilatation, and right rectum dilatation. In addition, general parameters are as follows: weight: 2280 g; length: 39 cm; head circumference: 26.3 cm; abdomen circumference: 31 cm; right thigh circumference: 17 cm, and left thigh circumference: 18 cm. LESSONS: US combined with MRI can not only provide reliable evidence for fetal CM in the third trimester but also offer crucial information to the pregnant women to establish clinic treatment programs as early as possible.

miRNA-101 promotes chondrogenic differentiation in rat bone marrow mesenchymal stem cells.

Effect and related mechanisms of miR-101 on the chondrogenic differentiation of rat bone marrow mesenchymal stem cells (MSCs) were investigated. The expression level of miR-101 was detected during chondrogenic differentiation. Three groups were established to study the potential function between miR-101 and chondrogenic differentiation: miR-NC group (negative control), miR-101 mimics (BMSCs transfected by miR-101 mimics) and mimics + inhibitor (BMSCs transfected by miR-101 mimics and inhibitor), after the induction of chondrogenic differentiation, the cell viability of MSCs and chondrogenic markers were determined, further, the expression level of Sox9 and Runx2 were detected. In our present research, miR-101 was found upregulated during chondrogenic differentiation of MSCs. Compared with the miR-NC group, the cell viability of MSCs was enhanced and the expression level of chondrogenic markers were respectively gained. The expression level of Sox9 was increased but the expression level of Runx2 was decreased by treatment of miR-101 mimics after induction of chondrogenic differentiation. However, these variations of the indicators were reversed by the intervention using the miR-101 inhibitor. Collectively, our research revealed promotion function of miR-101 on chondrogenic differentiation of MSCs, indicating that miR-101 could be a potential therapeutic strategy for the treatment of osteoarthritis (OA).

MicroRNA-1270 is associated with poor prognosis and its inhibition yielded anticancer mechanisms in human osteosarcoma.

In this work, we explored the aberrant expression pattern, clinical association, and functional regulations of microRNA-1270 (miR-1270) in osteosarcoma. Among in vitro osteosarcoma cell lines and in situ tissues of osteosarcoma patients, quantitative real time-PCR was used to examine their endogenous miR-1270 expression. Clinical correlation between endogenous miR-1270 expression and clinicopathological features of osteosarcoma patients, as well as cancer patients' overall survival, was statistically examined. MiR-1270 was downregulated in 143B and MG-63 cells by lentiviral transduction. The mechanistic effects of miR-1270 downregulation on osteosarcoma in vitro proliferation and migration, as well as in vivo tumorigenesis, were further examined. MiR-1270 was aberrantly upregulated in both in vitro osteosarcoma cell lines and in situ human tumors. Statistical analysis demonstrated endogenous miR-1270 was associated with poor clinical outcomes and shorter overall survival of osteosarcoma patients. Lentivirus-induced miR-1270 downregulation inhibited cancer in vitro proliferation and migration, as well as in vivo tumorigenesis. Aberrant upregulation miR-1270 may be a prognostic biomarker for osteosarcoma patients with poor clinical outcomes and shorter survival. Inhibition of miR-1270 may also be a potential therapeutic target for anticancer treatment in osteosarcoma. © 2018 IUBMB Life, 70(7):625-632, 2018.

JTC-801 exerts anti-proliferative effects in human osteosarcoma cells by inducing apoptosis.

BACKGROUND: The research of G protein-coupled receptors (GPCRs) is a promising strategy for drug discovery. In cancer therapy, there is a need to discover novel agents that can inhibit proliferation and induce apoptosis in cancer cells. JTC-801 is a novel GPCR antagonist with the function of reversing pain and anxiety symptoms. This study aims to investigate the antitumor effects of JTC-801 on human osteosarcoma cells (U2OS) and elucidate the underlying mechanism. MATERIALS AND METHODS: The Cell Counting Kit-8 assay was used to detect the viability of U2OS cells treated with JTC-801 in vitro. The cell apoptosis was evaluated using a flow cytometry assay with Annexin V-FITC/PI double staining. The inhibitory effect of JTC-801 on invasion and migration of U2OS cells were determined by the Transwell assays. Western blot assay was performed to measure the levels of proteins related to cell apoptosis and its mechanism. RESULTS: The JTC-801 significantly decreased the viability of U2OS cells (p < .05) as a result of its anti-proliferative effect through induction of apoptosis associated with activation of BAX, Caspase-3 and down-regulating BCL-2 expression. The invasive and migratory cells were obviously reduced after JTC-801 treatment (p < .05). Further, the phosphorylated AKT, mTOR and active p70 S6 protein kinase in the PI3K/AKT signaling pathway were obviously lessened in the JTC-801 treated U2OS group (p < .05). CONCLUSIONS: JTC-801 may exert osteosarcoma cell growth inhibition by promoting cell apoptosis, through PI3K/AKT signaling pathway participation.

Mangiferin inhibits apoptosis and oxidative stress via BMP2/Smad-1 signaling in dexamethasone-induced MC3T3-E1 cells.

Mangiferin is a xanthone glucoside, which possesses antioxidant, antiviral, antitumor and anti-inflammatory functions, and is associated with gene regulation. However, it remains unknown whether mangiferin protects osteoblasts, such as the MC3T3-E1 cell line, against glucocorticoid-induced damage. In the present study, MC3T3-E1 cells were treated with dexamethasone (Dex), which is a well-known synthetic glucocorticoid, in order to establish a glucocorticoid-induced cell injury model. After Dex and/or mangiferin treatment, cell viability, apoptosis and reactive oxygen species (ROS) production was measured by Cell Counting kit-8 (CCK-8) and flow cytometry, respectively, and the concentration of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and macrophage colony-stimulating factor (M-CSF) was measured by ELISA. The expression of bone morphogenetic protein 2 (BMP2), phosphorylated­SMAD family member 1 (p-Smad-1), t-Smad-1, osterix (OSX), osteocalcin (OCN), osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), B­cell lymphoma 2 (Bcl-2) and Bcl­2­associated X protein (Bax) was measured by real-time PCR and/or western blot analysis. The results indicated that pretreatment of MC3T3-E1 cells with mangiferin for 3 h prior to exposure to Dex for 48 h significantly attenuated Dex-induced injury and inflammation, as demonstrated by increased cell viability, and decreases in apoptosis, ROS generation, and the secretion of TNF-α, IL-6 and M-CSF. In addition, pretreatment with mangiferin markedly reduced Dex-induced BMP2 and p­Smad-1 downregulation, and corrected the expression of differentiation­ and apoptosis­associated markers, including alkaline phosphatase, OSX, OCN, OPG, RANK, RANKL, Bcl-2 and Bax, which were altered by Dex treatment. Similar to the protective effects of mangiferin, overexpression of BMP2 suppressed not only Dex-induced cytotoxicity, but also ROS generation, and the secretion of TNF-α, IL-6 and M-CSF. In conclusion, the results of the present study are the first, to the best of our knowledge, to demonstrate that mangiferin protects MC3T3-E1 cells against Dex-induced apoptosis and oxidative stress by activating the BMP2/Smad-1 signaling pathway.

Circulating Insulin-Like Growth Factor-1 Level and Ovarian Cancer Risk.

BACKGROUND/AIMS: Insulin-like growth factor-1 (IGF-1) has an important role in cells' proliferation, differentiation and apoptosis, and it may be involved in carcinogenesis. Several epidemiological studies assessed the association between circulating IGF-1 level and ovarian cancer risk, but there was still no conclusive finding. METHODS: A meta-analysis of published studies was performed to assess the association between circulating IGF-1 level and ovarian cancer risk. The summary odds ratio (OR) with 95% confidence interval (95%CI) was calculated through meta-analysis to evaluate the strength of the association. RESULTS: Five eligible studies were included into the meta-analysis, which involved a total of 2,028 cases of ovarian cancer and 4,625 controls. Meta-analysis of total 5 studies showed that high circulating IGF-1 level was correlated with decreased risk of ovarian cancer (OR = 0.84, 95%CI 0.74-0.97, P = 0.013). After adjusting for heterogeneity, high circulating IGF-1 level was still correlated with decreased risk of ovarian cancer (OR = 0.83, 95%CI 0.72-0.95, P = 0.007). Subgroup analysis by age showed that circulating IGF-1 level was not correlated with ovarian cancer risk in women both less than 55 years and more than 55 years. However, after adjusting for heterogeneity, high circulating IGF-1 level was correlated with decreased ovarian cancer risk in women less than 55 years (OR = 0.82, 95%CI 0.72-0.94, P = 0.004). CONCLUSION: Our meta-analysis suggests that high circulating IGF-1 level may be correlated with decreased ovarian cancer risk, especially in women less than 55 years. More studies are needed to further assess the association between circulating IGF-1 level and ovarian cancer risk in the future.

Key genes expressed in different stages of spinal cord ischemia/reperfusion injury.

The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. The damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24-hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplification, labeling, and hybridization were used to obtain the microRNA expression profiles of each group. Bioinformatics analysis confirmed four differentially expressed microRNAs (miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p) and their common target genes (Tmem69 and Cxcl10). Compared with the sham group, miR-22-3p was continuously upregulated in all three ischemia groups but was highest in the group with no reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identified the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury.

Diagnostic value of plasma lysophosphatidic acid levels in ovarian cancer patients: A case-control study and updated meta-analysis.

AIM: We investigated whether plasma levels of lysophosphatidic acid (LPA) could serve as a diagnostic indicator for assessing disease progression in ovarian cancer (OC) patients. MATERIAL AND METHODS: In this study, we enrolled 98 patients with OC, 70 patients with benign ovarian tumors and 75 healthy controls. Plasma levels of LPA and cancer antigen 125 (CA-125) were measured in all study subjects. The diagnostic values of LPA and CA-125 plasma levels were evaluated and an updated meta-analysis was performed to examine the association between LPA plasma levels and OC progression. Statistical analyses were performed with SPSS 18.0 and R 3.1.0 software. RESULTS: In our case-control study, OC patients showed significantly higher plasma LPA levels compared to patients with benign tumors and healthy controls (all P < 0.05). Plasma LPA levels exhibited higher diagnostic sensitivity (P = 0.008) and specificity (P = 0.042) in detecting OC, compared to an established marker, CA-125. Notably, the sensitivity for early stage OC was significantly higher for plasma LPA levels in comparison to CA-125 (P < 0.05). Consistent with this, the area under the receiver-operator curve was greater for LPA (0.899) in comparison to that for CA-125 (0.751). Further, meta-analysis showed that plasma LPA levels were significantly higher in OC patients compared to patients with benign tumors or healthy controls (all P < 0.05). CONCLUSION: Plasma LPA levels are elevated in OC patients and correlate with disease progression. Further, LPA shows higher sensitivity and specificity in OC diagnosis, compared to CA-125, especially in early stage OC.

p53 mediated apoptosis in osteosarcoma MG-63 cells by inhibition of FANCD2 gene expression.

PURPOSE: The aim of this study was to investigate the association between osteosarcoma (OS) and Fanconi anemia (FA) related pathways and the molecular mechanisms. METHODS: siRNA for Fanconi anemia complementation group D2 (FANCD2) was constructed and transfected into the osteosarcoma cell line MG-63 cells. Expression of TP53INP1, p53, p21, caspase-9, and caspase-3 mRNA in MG-63 cells were examined by real-time fluorescence quantitative PCR, and the protein levels were also determined by western blot. RESULTS: After silence of the FANCD2 gene in MG-63 cells, cell proliferation was inhibited, cell cycle was arrested and cell apoptosis was induced. The apoptosis was mediated by the p53 signaling pathway. After FANCD2 expression was inhibited, TP53INP1 gene expression was up-regulated, phosphorylation of p53 was promoted and the p21 protein was activated, leading to cell cycle arrested in G1, finally resulted in caspase-dependent cell apoptosis. CONCLUSIONS: Inhibition of FANCD2 gene expression can induce apoptosis of osteosarcoma cells, which indicated that FANCD2 played an important role in the development of osteosarcoma and it might be a potential target for treatment of osteosarcoma.

Plasma levels of lysophosphatidic acid in ovarian cancer versus controls: a meta-analysis.

BACKGROUND: In this study, using a meta-analysis approach, we examined the correlation between serum levels of lysophosphastidic acid (LPA) and ovarian cancer (OC). METHODS: Relevant published studies were identified from multiple scientific literature databases by using a pre-determined electronic and manual search strategy. The search results were screened through a multi-step process to select high-quality case-control studies suitable for the present meta-analysis. Mean values and standardized mean differences (SMD) were calculated for plasma LPA levels. Two investigators independently extracted the data from the studies and performed data analysis using STATA software version 12.0 (Stata Corp, College Station, TX, USA). RESULTS: Nineteen case-control studies met our selection criteria and contained a total of 980 OC patients, 872 benign controls and 668 healthy controls. Our meta-analysis results revealed that the plasma levels of LPA in OC patients were significantly higher than benign controls (SMD = 2.36, 95% CI: 1.61-3.10, P < 0.001) and healthy controls (SMD = 2.32, 95% CI: 1.77-2.87, P < 0.001). Subgroup analysis by ethnicity showed that the plasma LPA levels in OC patients were significantly higher than the benign controls only in Asian populations (SMD = 2.52, 95% CI: 1.79-3.25, P < 0.001). However, a comparison between healthy controls and OC patients revealed that, in both Asians and Caucasians, the OC patients displayed significantly higher plasma LPA levels compared to healthy controls (all P < 0.05). CONCLUSION: Our meta-analysis showed strong evidence that a significantly higher plasma LPA levels are present in OC patients, compared to benign controls and healthy controls, and plasma LPA levels may be used as a biomarker or target of OC.