Prognostic significance of the expression of HER family members in primary osteosarcoma

Wang, Shenglin; Zhong, Guang‐Xian; Wang, Xinwen; Yu, Fengqiang; Weng, Dan-Feng; Lin, Jianhua

doi:10.3892/ol.2018.8931

Cited by 16 publications

(19 citation statements)

References 41 publications

(51 reference statements)

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“…Surprisingly, one study reported a positive correlation between EGFR expression and good clinical outcome in high-grade OS patients, which might be due to the fact that patients with high EGFR levels show better responses to conventional therapies (Kersting et al, 2007). In contrast, another recent report found a significant correlation between high EGFR levels in OS and reduced patient survival (Wang et al, 2018). Since OS is a rare tumor, the few numbers of OS patients preclude a comprehensive investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Epidermal growth factor receptor (EGFR) expression occurs in 55-81% of all OS cases; however, its clinical relevance in OS development is still controversial (Oda et al, 1995;Wen et al, 2007;Do et al, 2009;Wang et al, 2018). EGFR can control c-Fos via the MAPK pathway, and changes in c-fos expression after anti-EGFR treatment in cell lines have been suggested to predict therapy success (Jimeno et al, 2006;Murphy & Blenis, 2006).…”

Section: Introductionmentioning

confidence: 99%

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EGFR is required for FOS‐dependent bone tumor development via RSK2/CREB signaling

et al. 2018

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Osteosarcoma (OS) is a rare tumor of the bone occurring mainly in young adults accounting for 5% of all childhood cancers. Because of the limited therapeutic options, there has been no survival improvement for OS patients in the past 40 years. The epidermal growth factor receptor (EGFR) is highly expressed in OS; however, its clinical relevance is unclear. Here, we employed an autochthonous c‐Fos‐dependent OS mouse model (H2‐c‐fosLTR) and human OS tumor biopsies for preclinical studies aimed at identifying novel biomarkers and therapeutic benefits of anti‐EGFR therapies. We show that EGFR deletion/inhibition results in reduced tumor formation in H2‐c‐fosLTR mice by directly inhibiting the proliferation of cancer‐initiating osteoblastic cells by a mechanism involving RSK2/CREB‐dependent c‐Fos expression. Furthermore, OS patients with co‐expression of EGFR and c‐Fos exhibit reduced overall survival. Preclinical studies using human OS xenografts revealed that only tumors expressing both EGFR and c‐Fos responded to anti‐EGFR therapy demonstrating that c‐Fos can be considered as a novel biomarker predicting response to anti‐EGFR treatment in OS patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

EGFR is required for FOS‐dependent bone tumor development via RSK2/CREB signaling

et al. 2018

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“…The grade of NLRP3 protein expression was scored from 0 to 3 according to the staining intensity of osteosarcoma cells (0, negative; 1, weakly positive; 2, moderately positive; 3, strongly positive). The mean percentage of positive osteosarcoma cells was also scored from 1 to 3 (1, <25%; 2, 25%–75%; 3, >75%) ( Wang et al, 2018 ). The final scores were the grade multiplied by the percentage score of tumor cells, giving final scores of 0, 1, 2, 3, 4, 6, 9.…”

Section: Methodsmentioning

confidence: 99%

NLRP3 Overexpression Associated With Poor Prognosis and Presented as an Effective Therapeutic Target in Osteosarcoma

et al. 2021

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Despite the development of diagnostic and treatment strategies, the survival outcome of patients with osteosarcoma remains poor. Nod-like receptor protein 3 (NLRP3) plays a crucial role in the inflammasome pathway, which is related to the progression of various tumors. However, the effect of NLRP3 on osteosarcoma has not yet been well explored. Our study aimed to investigate the role of NLRP3 in the malignant biological behavior of osteosarcoma as well as its therapeutic value. Immunohistochemistry was applied to investigate the NLRP3 expression in osteosarcoma and osteochondroma specimens. Cell Counting Kit-8, colony formation, wound healing, transwell, and flow cytometry assays were used to explore the contribution of NLRP3 to the proliferation, migration, invasion, apoptosis and cell cycle distribution of osteosarcoma cells in vitro. Western blot was performed to evaluate the expression of NLRP3 and the related proteins in osteosarcoma cell lines after the blockade of NLRP3 using CY-09 and lentivirus intervention. Furthermore, tumor formation assay was used to analyze the effect of NLRP3 on the growth of osteosarcoma in vivo. The results showed that the NLRP3 protein was overexpressed in osteosarcoma, which was independently correlated with the poor prognosis of patients. Moreover, NLRP3 suppression by the inhibitor of CY-09 or lentivirus-induced gene knockdown inhibited the cell proliferation, migration, invasion and promoted the cell apoptosis and G1 cell cycle arrest in osteosarcoma via targeting the inflammasome pathway. Our in vivo results confirmed that the inhibition of NLRP3 suppressed the tumor formation of osteosarcoma. In conclusion, NLRP3 may be regarded as an independent prognostic biomarker and a potential therapeutic target for osteosarcoma.

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“…Overexpression of EGFR is related to survival, invasion, metastasis, drug resistance, and poor prognosis of tumor [58], for example, EGFR is considered as an indicator of inferior prognosis in node-negative breast cancer [59]. EGFR was reported to be abnormally expressed in osteosarcoma, and the expression as well as amplification of EGFR were observed in the osteosarcoma with high grade (PMID: [60,61]). FAS is an essential enzyme in the process of lipogenesis, and could effectively maintain the energy homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Signature of Osteosarcoma Based on 14 Autophagy-Related Genes

Wei

Yan

et al. 2021

Pathol. Oncol. Res.

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Background: Osteosarcoma is a common malignancy of bone with inferior survival outcome. Autophagy can exert multifactorial influence on tumorigenesis and tumor progression. However, the specific function of genes related to autophagy in the prognosis of osteosarcoma patients remains unclear. Herein, we aimed to explore the association of genes related to autophagy with the survival outcome of osteosarcoma patients.Methods: The autophagy-associated genes that were related to the prognosis of osteosarcoma were optimized by LASSO Cox regression analysis. The survival of osteosarcoma patients was forecasted by multivariate Cox regression analysis. The immune infiltration status of 22 immune cell types in osteosarcoma patients with high and low risk scores was compared by using the CIBERSORT tool.Results: The risk score model constructed according to 14 autophagy-related genes (ATG4A, BAK1, BNIP3, CALCOCO2, CCL2, DAPK1, EGFR, FAS, GRID2, ITGA3, MYC, RAB33B, USP10, and WIPI1) could effectively predict the prognosis of patients with osteosarcoma. A nomogram model was established based on risk score and metastasis.Conclusion: Autophagy-related genes were identified as pivotal prognostic signatures, which could guide the clinical decision making in the treatment of osteosarcoma.

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Prognostic significance of the expression of HER family members in primary osteosarcoma

Cited by 16 publications

References 41 publications

EGFR is required for FOS‐dependent bone tumor development via RSK2/CREB signaling

EGFR is required for FOS‐dependent bone tumor development via RSK2/CREB signaling

NLRP3 Overexpression Associated With Poor Prognosis and Presented as an Effective Therapeutic Target in Osteosarcoma

Prognostic Signature of Osteosarcoma Based on 14 Autophagy-Related Genes

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