The role of chemotherapy and radiotherapy in localized extraskeletal osteosarcoma

Heng, Marilyn; Gupta, Abha; Chung, Peter; Healey, John H.; Vaynrub, Max; Rose, Peter S.; Houdek, Matthew T.; Lin, Patrick P.; Bishop, Andrew J.; Hornicek, Francis J.; Lozano-Calderón, Santiago; Holt, Ginger E.; Han, Ilkyu; Biau, David; Niu, Xiaohui; Bernthal, Nicholas M.; Ferguson, Peter C.; Wunder, Jay S.; Ueda, Takafumi; Kakunaga, Shigeki; Kawai, Akira; Sugiura, Hideshi; Kidani, Teruki; Kunisasa, Toshiyuki; Ozaki, Toshifumi; Ae, Keisuke; Nagano, Akihito; Ohno, Takatoshi; Hiraoka, Koji; Yamamoto, Norio; Tsuchiya, Hiroyuki; Matsumoto, Yoshihiro; Yanagawa, Takashi; Nakayama, Robart; Morioka, Hideo; Kubo, Toru; Simose, Shoji; Yamagami, Yoshiki; Yamamoto, Toshiyuki; Kawasaki, Motohiro; Torigoe, Tomoaki; Yazawa, Yasuo; Akiyama, Tsuyoshi; Gokita, Tabu; Manabe, Jun; Kaya, Mitsunori; Emori, Makoto; Nakamura, Tomoki; Matsumine, Akihiko; Sugihara, Shinsuke; Yokouchi, Masahiro; Komiya, Setsuro; Suehara, Yoshiyuki; Takagi, Tatsuya; Kawamoto, Teruya; Wasa, Junji; Yonemoto, Tsukasa; Ishii, Takeshi; Baba, Ichiro; Hoshi, Manabu; Hamada, Kenichiro; Naka, Norifumi; Sotobori, Tsukasa; Araki, Nobuhito; Okuma, Tomotake; Goto, Takahiro; Kobayashi, Hiroshi; Kawano, Hirotaka; Hosaka, Masami; Futani, Hiroyuki; Hiraga, Hiroaski; Nishida, Yoshihiro; Griffin, Anthony M.; Razak, Albiruni R. Abdul; Shultz, David; Catton, Charles; Robinson, Steven I.; Patel, Shreyaskumar; Lewis, Valerae O.; Guadagnolo, B. Ashleigh; DeLaney, Thomas F.; Wang, Haotong; Raskin, Kevin A.; Callan, Alexandra K.; Henshaw, Robert M.; Isler, Marc; Mottard, Sophie; Chen, Wei-Ming; Traub, Frank; Chen, Tom Wei‐Wu; Turcotte, Robert; Davidson, Darin; Tunn, Per‐Ulf; Loong, Herbert H.; Ghert, Michelle; Werier, Joel; Clarkson, Paul W.; Abraham, John A.

doi:10.1016/j.ejca.2019.07.029

Cited by 63 publications

(51 citation statements)

References 22 publications

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“…Over the recent decades, radiotherapy and chemotherapy for tumors have grew boomingly. However, the 5-year survival of osteosarcoma remained unsatisfactory (Ritter and Bielack, 2010;Kansara et al, 2014;Heng et al, 2020). It is imperative to develop effective methods to classify the patients according their risk score, and conduct reasonable individualized and targeted therapy.…”

Section: Discussionmentioning

confidence: 99%

Expression of Lipid-Metabolism Genes Is Correlated With Immune Microenvironment and Predicts Prognosis in Osteosarcoma

Lei

et al. 2021

Front. Cell Dev. Biol.

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ObjectivesOsteosarcoma was the most popular primary malignant tumor in children and adolescent, and the 5-year survival of osteosarcoma patients gained no substantial improvement over the past 35 years. This study aims to explore the role of lipid metabolism in the development and diagnosis of osteosarcoma.MethodsClinical information and corresponding RNA data of osteosarcoma patients were downloaded from TRGET and GEO databases. Consensus clustering was performed to identify new molecular subgroups. ESTIMATE, TIMER and ssGSEA analyses were applied to determinate the tumor immune microenvironment (TIME) and immune status of the identified subgroups. Functional analyses including GO, KEGG, GSVA and GSEA analyses were conducted to elucidate the underlying mechanisms. Prognostic risk model was constructed using LASSO algorithm and multivariate Cox regression analysis.ResultsTwo molecular subgroups with significantly different survival were identified. Better prognosis was associated with high immune score, low tumor purity, high abundance of immune infiltrating cells and relatively high immune status. GO and KEGG analyses revealed that the DEGs between the two subgroups were mainly enriched in immune- and bone remodeling-associated pathways. GSVA and GSEA analyses indicated that, lipid catabolism downregulation and lipid hydroxylation upregulation may impede the bone remodeling and development of immune system. Risk model based on lipid metabolism related genes (LMRGs) showed potent potential for survival prediction in osteosarcoma. Nomogram integrating risk model and clinical characteristics could predict the prognosis of osteosarcoma patients accurately.ConclusionExpression of lipid-metabolism genes is correlated with immune microenvironment of osteosarcoma patients and could be applied to predict the prognosis of in osteosarcoma accurately.

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Section: Discussionmentioning

confidence: 99%

Expression of Lipid-Metabolism Genes Is Correlated With Immune Microenvironment and Predicts Prognosis in Osteosarcoma

Lei

et al. 2021

Front. Cell Dev. Biol.

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“…Although most sarcoma harbors distinct biologic features, the primary treatment approach for locally advanced or unresectable disease often incorporates cytotoxic chemotherapy (Hashimoto et al, 2020;Heng et al, 2020;Lin et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel Immune Infiltration-Related ceRNA Network and Prognostic Model for Sarcoma

Shi

et al. 2021

Front. Cell Dev. Biol.

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Due to the rarity and heterogeneity, it is challenging to explore and develop new therapeutic targets for patients with sarcoma. Recently, immune cell infiltration in the tumor microenvironment (TME) was widely studied, which provided a novel potential approach for cancer treatment. The competing endogenous RNA (ceRNA) regulatory network has been reported as a critical molecular mechanism of tumor development. However, the role of the ceRNA regulatory network in the TME of sarcoma remains unclear. In this study, gene expression data and clinical information were obtained from The Cancer Genome Atlas (TCGA) sarcoma datasets, and an immune infiltration-related ceRNA network was constructed, which comprised 14 lncRNAs, 13 miRNAs, and 23 mRNAs. Afterward, we constructed an immune infiltration-related risk score model based on the expression of IRF1, MFNG, hsa-miR-940, and hsa-miR-378a-5p, presenting a promising performance in predicting the prognosis of patients with sarcoma.

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“…CLEC3A knockdown promotes chemosensitivity of OS cells to doxorubicin and cisplatin. chemotherapy resistance is an important reason for the failure of oS treatment (12). To determine whether the genetic knockdown of clec3a can promote chemosensitivity in OS cells, MG63 and SaOS-2 cells were treated with doxorubicin (doX) and cisplatin (cddP) for 24, 48 and 72 h. The ic 50 values of DOX and CDDP for MG63 and SaoS-2 cells at 24, 48 and 72 h are presented in Table ii.…”

Section: Inhibition Of Clec3a Decreases Os Cell Proliferation and Indmentioning

confidence: 99%

Suppression of CLEC3A inhibits osteosarcoma cell proliferation and promotes their chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway

Ren¹,

Pan²,

Hou³

et al. 2020

Mol Med Report

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osteosarcoma (oS) is a primary malignant tumor that occurs in bone, and mainly affects children and adolescents. c-type lectin domain family 3 member a (clec3a) is a member of the c-type lectin superfamily, which regulates various biological functions of cells. The present study aimed to identify the effects and related mechanisms of clec3a in the proliferation and chemosensitivity of oS cells. The expression of clec3a in oS was analyzed using the Gene Expression Omnibus data profile GSE99671, and its expression in OS samples was verified using reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical staining. The relationship between the expression of clec3a and clinical traits in patients with oS was also analyzed, including age, tumor size, TnM stage and lymph node metastasis. cell counting Kit-8 assays, colony formation assays and cell cycle distribution analysis were used to determine the roles of clec3a in the proliferation and chemosensitivity of OS cells. Finally, RT-qPCR and western blotting were used to demonstrate the relationship between clec3a and the aKT1/mTor/hypoxia-inducible factor 1-α (HiF1α) pathway. Both the mrna and protein expression levels of clec3a were increased in oS tissues compared with adjacent non-tumor tissues, and this was positively associated with TnM stage and lymph node metastasis. The genetic knockdown of clec3a with small interfering rna decreased oS cell proliferation and colony formation, and induced G1 phase arrest, whereas the overexpression of clec3a increased oS cell proliferation and colony formation, and alleviated G1 phase arrest. The suppression of clec3a also promoted enhanced the chemosensitivity of oS cells to doxorubicin (doX) and cisplatin (cddP); it also inhibited the expression of aKT1, mTor and HiF1α, further to the nuclear localization of HiF1α, and HiF1α target gene expression levels, including VeGF, GluT1 and Mcl1 were also decreased. Furthermore, treatment with the aKT activator Sc79 blocked the inhibitory effects of clec3a silencing in oS cells. in conclusion, these findings suggested that CLEC3A may function as an oncogene in oS, and that the suppression of clec3a may inhibit oS cell proliferation and promote chemosensitivity through the aKT1/mTor/HiF1α signaling pathway.

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The role of chemotherapy and radiotherapy in localized extraskeletal osteosarcoma

Cited by 63 publications

References 22 publications

Expression of Lipid-Metabolism Genes Is Correlated With Immune Microenvironment and Predicts Prognosis in Osteosarcoma

Expression of Lipid-Metabolism Genes Is Correlated With Immune Microenvironment and Predicts Prognosis in Osteosarcoma

Development of a Novel Immune Infiltration-Related ceRNA Network and Prognostic Model for Sarcoma

Suppression of CLEC3A inhibits osteosarcoma cell proliferation and promotes their chemosensitivity through the AKT1/mTOR/HIF1α signaling pathway

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