microRNA-138-5p as a Worse Prognosis Biomarker in Pediatric, Adolescent, and Young Adult Osteosarcoma

Roberto, Gabriela Molinari; Lira, Régia Caroline Peixoto; Delsin, Lara Elis Alberici; Vieira, Gabriela Maciel; Silva, Marcela Oliveira; Hakime, Rodrigo Guedes; Yamashita, Mauricio Eiji de Almeida Santos; Engel, Edgard Eduard; Scrideli, Carlos Alberto; Tone, Luíz Gonzaga; Brassesco, María Sol

doi:10.1007/s12253-019-00633-0

Cited by 13 publications

(12 citation statements)

References 42 publications

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“…Expression of miR-138-5p is increased in SCI tissues and in vitro SCI cell models. miR-138-5p belongs to the miR-138 family that has previously been shown to play an important role in various cancers (21)(22)(23). The levels of mir-138-5p in the blood of patients with SCI and the spinal tissues of SCI rats were assessed by RT-qPCR.…”

Section: Resultsmentioning

confidence: 99%

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MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

Chen

Qin

2020

Mol Med Report

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Micrornas (mirs) play an important role in the development and progression of spinal cord injury (Sci). The role of mir-138-5p in Sci was investigated in the present study. The anti-inflammatory effects of miR-138-5p and underlying mechanisms were investigated in an Sci rat model and in vitro model. reverse transcription-quantitative Pcr (rT-qPcr) was used to examine the expression of mir-138-5p in the Sci in vivo and in vitro models, as well as patients with Sci; it was found that miR-138-5p was significantly upregulated in Sci. Bioinformatics and dual-luciferase reporter assays were performed to predict and confirm the binding sites between mir-138-5p and the 3'untranslated region of sirtuin 1 (SirT1). Then, the expression of SirT1 was detected via rT-qPcr and western blotting, indicating downregulation of SIRT1 in SCI. PC12 cells were transfected with miR-138-5p inhibitor, inhibitor control or miR-138-5p inhibitor + SIRT1 small interfering RNA for 48 h, and then subjected to lipopolysaccharide (100 ng/ml) treatment for 4 h. Then, MTT assay, flow cytometry and eliSa experiments were performed to analyze cell viability, apoptosis, and the levels of tumor necrosis factor-α, interleukin (il)-1β and il-6. Findings suggested that downregulation of miR-138-5p increased PC12 cell viability, inhibited cell apoptosis and attenuated proinflammatory responses, which may result in amelioration of Sci. However, all these effects were reversed by SIRT1 knockdown. Finally, it was observed that miR-138-5p altered the related protein expression of the PTen/aKT pathway. These results indicated that miR-138-5p could regulate inflammatory responses and cell apoptosis in SCI models by modulating the PTEN/AKT signaling pathway via SirT1, thus playing an important role in the development of Sci. collectively, the present study demonstrated that miR-138-5p may be a novel therapeutic target for the treatment of Sci. Materials and methodsClinical samples. a total of 18 serum specimens from patients with Sci (age range, 27-58 years; 12 male patients and 6 female MicroRNA-138-5p regulates the development of spinal cord injury by targeting SIRT1 JincHuan cHen and ruJie Qin department of Spine Surgery, The First People's Hospital of lianyungang, lianyungang, Jiangsu 222000, P.r. china

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Section: Resultsmentioning

confidence: 99%

“…altered expression of various miRNAs following traumatic SCI has been observed in adult rats (20). miR-138-5p, a miRNA that has been studied in a variety of tumors (21)(22)(23), has also been found to play an important role in Parkinson's disease (24). However, so far, the role of miR-138-5p in SCI has not been reported.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

Chen

Qin

2020

Mol Med Report

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“…Finally, despite for its advantages in this cohort, it is noteworthy that NPS is a non-specific predictor for osteosarcoma and thus unavoidably possesses its intrinsic weaknesses and limitations. By combining NPS with some specific biomarkers for osteosarcoma, such as miR-138-5p, circ_0000502, lncRNA TP73-AS1, and circ-NT5C2, numerous novel, specific, and multidimensional prognostic indexes can be formulated, but their prognostic performances need to be verified in future studies [10,12,66,67]. So, future studies can concentrate on screening optimal combinations of NPS and new biomarkers for osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma

et al. 2020

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Background: This study aimed to evaluate the clinical significance of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma. Methods: The clinical data of 133 osteosarcoma patients between January 2011 and February 2018 in our hospital was retrospectively collected and analyzed. NPS was calculated from four parameters, including serum albumin level, serum total cholesterol (TC), lymphocyte-to-monocyte ratio (LMR), and neutrophil-to-lymphocyte ratio (NLR). Patients were divided into three groups (group 1-3) based on NPS. The relationships between NPS and clinical features, overall survival (OS), and progression-free survival (PFS) were analyzed. Two prediction models based on NPS and clinical parameters were developed: clinical parameters model (model A), and the combined model of NPS and clinical parameters (model B). Their predictive performances were further evaluated and compared. Results: The median follow-up time of this cohort was 46.0 (range, 5-75) months, while the median OS and PFS was 40 (range, 5-75) months and 36 (range, 5-71) months, respectively. NPS was significantly correlated with gender, tumor location, Enneking stage, pathological fracture, local recurrence, and metastasis (all P < 0.05). Variables of NPS, Enneking stage, local recurrence, metastasis, and NLR were confirmed as independent prognostic factors for OS and PFS by univariate and multivariate Cox analysis. Prediction model B obtained larger AUCs for OS and PFS and showed better consistency between nomogram-predicted and actual survival than that of model A at the follow-up time of 1-, 3-, and 5-year. Conclusions: NPS was a novel, reliable, and multidimensional prognostic scoring system with favorable predictive performance for patients with osteosarcoma.

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“…However, these factors were not associated with speci c therapy, which has proven effective in improving clinical outcomes directly. Recently, miR-138-5p, miR-1285-3p, miR-199a-3p, and ERp29 were reported as prognostic factors for osteosarcoma [5][6][7][8][9] : however, these markers are costly and inconvenient to measure, and cannot be used in the standard management of patients yet.…”

Section: Discussionmentioning

confidence: 99%

“…Some types of cancer have a speci c marker revealing the grade or prognosis ; however, osteosarcoma has no oncological marker re ecting its prognosis. Recently, miR-138-5p, miR-1285-3p, miR-199a-3p, and ERp29 were reported as prognostic factors for osteosarcoma [5][6][7][8][9], but these markers are costly and inconvenient to measure, and cannot be used in the standard management of patients yet. The simple measurement of prognostic factors is extremely useful and has been widely accepted for guiding the treatment course of patients.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment C-reactive protein and neutrophil counts as a predictor of metastasis in patients with osteosarcoma

Araki

Yamamoto

Hayashi

et al. 2020

Preprint

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Background: Systemic inflammation responses have been associated with cancer development, progression and metastasis. However, little is known about the risk of metastasis based on inflammatory-based scores in patients with osteosarcoma before treatment. We therefore estimated the predictive value of these parameters for metastasis in osteosarcoma.Methods: A total of 54 osteosarcoma patients were enrolled in this retrospective study. All had been diagnosed histologically, and their laboratory data at the first visit were collected from medical records. The lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), monocyte-neutrophil ratio (MNR), platelet-lymphocyte ratio (PLR), Glasgow prognostic score (GPS), neutrophil-platelet score (NPS), neutrophil counts (NC), lymphocyte counts (LC), monocyte counts (MC), and C-reactive protein (CRP) were evaluated.Results: High values of CRP, PLR, MNR, and NPS and a low NC were significantly associated with metastasis of osteosarcoma patients in the univariate analysis. A multivariate Cox regression analysis revealed that a high CRP level (>0.6mg/dL) (hazard ratio=9.7, 95% confidence interval=3.0-31 ; p=0.00010) and low NC (<4087/µL) (hazard ratio=0.13, 95% confidence interval =0.040-0.42 ; p=0.00080) were risk factors significantly associated with metastasis of osteosarcoma patients.Conclusions: Our study demonstrated that the combination of a high CRP level and low NC before treatment was a useful inflammatory-based prognostic indicator for metastasis in patients with osteosarcoma.

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microRNA-138-5p as a Worse Prognosis Biomarker in Pediatric, Adolescent, and Young Adult Osteosarcoma

Cited by 13 publications

References 42 publications

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

MicroRNA‑138‑5p regulates the development of spinal cord injury by targeting SIRT1

Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma

Pretreatment C-reactive protein and neutrophil counts as a predictor of metastasis in patients with osteosarcoma

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