STAT1, IGF1, RAC1, and MDM2 Are Associated with Recurrence of Giant Cell Tumor of Bone

Chen, Shuxin; Du, Zhifeng; Wu, Bing‐Li; Shen, Huiyang; Liu, Chunpeng; Xue-li, Qiu; Zhang, Yufeng; Xu, Li‐Yan; Li, En‐Min; Zhong, Zhigang

doi:10.1155/2018/4564328

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…Comparing the osteosarcoma, Ewing sarcoma, and GCT groups, the overexpression of the IGF-1 axis was more prominent in osteosarcoma and Ewing sarcoma compared to GCT which might be influenced by higher tumor grades and disease stages in these groups. It was shown that the expression level of IGF-1 in recurrent GCT was significantly higher than in non-recurrent GCT subjects (33); however, GCT cases in our study were GCT patients without recurrence. Most of the studies in the literature regarding the IGF-1 axis in bone tumor pathogenesis are focused on determining the functional mechanism of this axis.…”

Section: Discussioncontrasting

confidence: 69%

Evaluating the local expression pattern of IGF-1R in tumor tissues and the circulating levels of IGF-1, IGFBP-1, and IGFBP-3 in the blood of patients with different primary bone tumors

Vaezi

Eghtedari²,

Safizadeh³

et al. 2023

Front. Oncol.

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IntroductionThe present study tried to provide insights into the expression pattern and diagnostic significance of the IGF-1 axis main mediators in three main primary bone tumor types with different degrees of severity.MethodsThe real-time qRT-PCR (to analyze IGF-1R gene expression), the immunohistochemistry (to measure IGF-1R protein), and the ELISA assay (to assess the circulating level of IGF-1, IGFBP-1, and IGFBP-3) were applied to confirm this hypothesis. A total number of 180 bone tissues (90 tumors and 90 noncancerous adjacent tissues) and 120 blood samples drained from 90 patients with bone tumors and 30 healthy controls were enrolled in the study. The association of insulin-like growth factor (IGF)-1 axis expression pattern with the patient’s clinical pathological characteristics and tumor aggressive features, the diagnostic and predictive values were assessed for all tumor groups.ResultsA significantly elevated level of IGF-1R gene and protein was detected in bone tumors compared to the noncancerous bone tissues that were prominent in osteosarcoma and Ewing sarcoma compared to the GCT group. The positive association of the IGF-1R gene and protein level with tumor grade, metastasis, and recurrence was detected in the osteosarcoma and Ewing sarcoma groups. The circulating level of IGF-1, IGFPB-1, and IGFBP-3 were increased in osteosarcoma and Ewing sarcoma and GCT groups that were correlated significantly to the tumor severity. The ability of the IGF-1 axis to discriminate between bone tumors also malignant and benign tumors was considerable.DiscussionIn summary, our data suggested that IGF-1R, IGF-1, IGFBP-1, and IGFBP-3 levels are associated with bone tumor malignancy, metastasis, and recurrence that might serve as biomarkers for osteosarcoma and Ewing sarcoma recurrence.

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Section: Discussioncontrasting

confidence: 69%

Evaluating the local expression pattern of IGF-1R in tumor tissues and the circulating levels of IGF-1, IGFBP-1, and IGFBP-3 in the blood of patients with different primary bone tumors

Vaezi

Eghtedari²,

Safizadeh³

et al. 2023

Front. Oncol.

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“…Multiple genes influence the biological behaviour of prostate cancer cells by regulating MMP1 52–54 . STAT1 may activate the immune system of cancer patients 55,56 . However, abnormal low expression of STAT1 may create conditions for tumour immune escape 57 .…”

Section: Discussionmentioning

confidence: 99%

“… 52 , 53 , 54 STAT1 may activate the immune system of cancer patients. 55 , 56 However, abnormal low expression of STAT1 may create conditions for tumour immune escape. 57 At present, some studies have confirmed that some kinds of cancer cells, including melanoma, squamous cell carcinoma and gastric carcinoma, can achieve the purpose of immune escape by downregulation of STAT1 expression.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral immune heterogeneity of prostate cancer characterized by typing and hub genes

Han¹,

Zhou²,

Zhang³

et al. 2022

J Cellular Molecular Medi

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Discordant abundances of different immune cell subtypes is regarded to be an essential feature of tumour tissue. Direct studies in Prostate cancer (PC) of intratumoral immune heterogeneity characterized by immune cell subtype, are still lacking. Using the single sample gene set enrichment analysis (ssGSEA) algorithm, the abundance of 28 immune cells infiltration (ICI) were determined for PC. A NMF was performed to determine tumour-sample clustering based on the abundance of ICI and PFS information. Hub genes of clusters were identified via weighted gene co-expression network analysis (WGCNA). The multivariate dimensionality reduction analysis of hub genes expression matrix was carried out via principal component analysis (PCA) to obtain immune score (IS). We analysed the correlation between clustering, IS and clinical phenotype. We divided the 495 patients into clusterA (n = 193) and clusterB (n = 302) on the basis of ICI and PFS via NMF. The progression-free survival (PFS) were better for clusterA than for clusterB (p < 0.001). Each immune cell subtypes was more abundant in clusterA than in clusterB (p < 0.001). The expression levels of CTAL-4 and PD-L1 were lower in clusterB than in clusterA (p < 0.001 and p = 0.006). We obtained 103 hub genes via WGCNA. In the training and validation cohorts, the prognosis of high IS group was worse than that of the low IS group (p < 0.05). IS had good predictive effect on 5-year PFS. The expression of immune checkpoint genes was higher in the low IS group than in the high IS group (p < 0.01). Patients with low IS and receiving hormone therapy had better prognosis than other groups. The combination of IS and clinical characteristics including lymph node metastasis and gleason score can better differentiate patient outcomes than using it alone. IS was a practical algorithm to predict the prognosis of patients. Advanced PC patients with low IS may be more sensitive to hormone therapy. CXCL10, CXCL5, MMP1, CXCL12, CXCL11, CXCL2, STAT1, IL-6 and TLR2 were hub genes, which may drive the homing of immune cells in tumours and promote immune cell differentiation.

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“…Similarly, the group of Chen et al [ 50 , 51 ] assessed differentially expressed genes in the recurrent GCTB through microarray and IHC, identifying four genes with a statistically significant association with GCTB recurrence: mouse double minute 2 homolog (MDM2) ( p = 0012), insulin-like growth factor 1 (IGF1) ( p = 0033), signal transducer and activator of transcription 1 (STAT1) ( p = 0026) and Rac family small GTPase 1 (RAC1) ( p = 0007), suggesting they might be used as biomarkers for GCTB recurrence.…”

Section: Gctb Cytology Histopathogenesis and New Biomarkers In Molecular Targeted Therapy Eramentioning

confidence: 98%

State of the Art and New Concepts in Giant Cell Tumor of Bone: Imaging Features and Tumor Characteristics

Parmeggiani

Miceli

Errani

et al. 2021

Cancers

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Giant cell tumor of bone (GCTB) is classified as an intermediate malignant tumor due to its locally aggressive behavior, burdened by high local recurrence rate. GCTB accounts for about 4–5% of all primary bone tumors and typically arises in the metaphysis and epiphyses of the long tubular bones. Mutation of gene H3F3A is at the basis of GCTB etiopathogenesis, and its immunohistochemical expression is a valuable method for practical diagnosis, even if new biomarkers have been identified for early diagnosis and for potential tumor recurrence prediction. In the era of computer-aided diagnosis, imaging plays a key role in the assessment of GCTB for surgical planning, patients’ prognosis prediction and post treatment evaluation. Cystic changes, penetrating irregular margins and adjacent soft tissue invasion on preoperative Magnetic Resonance Imaging (MRI) have been associated with a higher rate of local recurrence. Distance from the tumor edge to the articular surface and thickness of unaffected cortical bone around the tumor should be evaluated on Computed Tomography (CT) as related to local recurrence. Main features associated with local recurrence after curettage are bone resorption around the graft or cement, soft tissue mass formation and expansile destruction of bone. A denosumab positive response is represented by a peripherical well-defined osteosclerosis around the lesion and intralesional ossification. Radiomics has proved to offer a valuable contribution in aiding GCTB pre-operative diagnosis through clinical-radiomics models based on CT scans and multiparametric MR imaging, possibly guiding the choice of a patient-tailored treatment. Moreover, radiomics models based on texture analysis demonstrated to be a promising alternative solution for the assessment of GCTB response to denosumab both on conventional radiography and CT since the quantitative variation of some radiomics features after therapy has been correlated with tumor response, suggesting they might facilitate disease monitoring during post-denosumab surveillance.

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STAT1, IGF1, RAC1, and MDM2 Are Associated with Recurrence of Giant Cell Tumor of Bone

Cited by 4 publications

References 24 publications

Evaluating the local expression pattern of IGF-1R in tumor tissues and the circulating levels of IGF-1, IGFBP-1, and IGFBP-3 in the blood of patients with different primary bone tumors

Evaluating the local expression pattern of IGF-1R in tumor tissues and the circulating levels of IGF-1, IGFBP-1, and IGFBP-3 in the blood of patients with different primary bone tumors

Intratumoral immune heterogeneity of prostate cancer characterized by typing and hub genes

State of the Art and New Concepts in Giant Cell Tumor of Bone: Imaging Features and Tumor Characteristics

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