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Identification of a biomarker to predict doxorubicin/cisplatin chemotherapy efficacy for osteosarcoma patients by 4D data-independent acquisition (DIA) mass spectrometry with parallel reaction monitoring (PRM) verification

ABSTRACT: We analyzed the differentially expressed proteins in 37 resected tissue samples from osteosarcoma patients using paraffin- embedded specimens and 4D data-independent acquisition (DIA) quantitative mass spectrometry to investigate biomarkers for predicting the efficacy of doxorubicin/cisplatin chemotherapy

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Osteosarcoma

SUBMITTER: Xiaoyu Zhang

LAB HEAD: Qiong Ma

PROVIDER: PXD051097 | Pride | 2024-10-17

REPOSITORIES: Pride

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Publications

Identification of a biomarker to predict doxorubicin/cisplatin chemotherapy efficacy in osteosarcoma patients using primary, recurrent and metastatic specimens.

Ma Qiong Q Sun Jin J Liu Qiao Q Fu Jin J Wen Yanhua Y Zhang Fuqin F Wu Yonghong Y Zhang Xiaoyu X Gong Li L Zhang Wei W

Translational oncology 20240816

<h4>Background</h4>Doxorubicin and cisplatin are both first-line chemotherapeutics for osteosarcoma (OS) treatment. However, the efficacy of doxorubicin/cisplatin chemotherapy varies considerably. Thus, identifying an efficient diagnostic biomarker to distinguish patients with good and poor responses to doxorubicin/cisplatin chemotherapy is of paramount importance.<h4>Methods</h4>To predict the efficacy of doxorubicin/cisplatin chemotherapy, we analyzed the differentially expressed proteins in 3 ...[more]

PMID: 39153366

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caArray_lau-00212: Expression profiles of osteosarcoma that can predict response to chemotherapy

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Cisplatin and doxorubicin chemotherapy alters gut microbiota in a murine osteosarcoma model.

Project description:The gut microbiota is closely associated with tumor progression and treatment in a variety of cancers. However, the alteration of the gut microbiota during the progression and chemotherapy of osteosarcoma remains poorly understood. This study aimed to explore the relationship between dysbiosis in the gut microbiota during osteosarcoma growth and chemotherapy treatment. We used BALB/c nude mice to establish osteosarcoma xenograft tumor models and administered cisplatin (CDDP) or doxorubicin (DOX) intraperitonially once every 2 days for a total of 5 times to establish effective chemotherapy models. Fecal samples were collected and processed for 16S rRNA sequencing to analyze the composition of the gut microbiota. We observed that the abundances of Colidextribacter, Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG-010, Lachnospiraceae_UCG-006, and Lachnoclostridium decreased, and the abundances of Alloprevotella and Enterorhabdus increased in the osteosarcoma mouse model group compared to those in the control group. In addition, genera, such as Lachnoclostridium and Faecalibacterium were more abundant in chemotherapy-treated mice than those in saline-treated mice. Additionally, we observed that alterations in some genera, including Lachnoclostridium and Colidextribacter in the osteosarcoma animal model group returned to normal after CDDP or DOX treatment. Furthermore, the function of the gut microbiota was inferred through PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), which indicated that metabolism-related microbiota was highly enriched and significantly different in each group. These results indicate correlations between dysbiosis of the gut microbiota and osteosarcoma growth and chemotherapy treatment with CDDP or DOX and may provide novel avenues for the development of potential adjuvant therapies.

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MicroRNA expression in a chondroblastic osteosarcoma

Project description:A chondroblastic osteosarcoma was surgically resected. We performed small RNA sequencing to quantify the microRNAs/ small RNAs expression in the resulting library.

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Genes involved in doxorubicin drug resistance in 143b osteosarcoma cell line

Project description:The study was done to identify the differentially expressed genes in response to Doxorubicin drug resistance in the 143B human osteosarcoma cell line, using the Microarray technology. Keywords: drug resistance; dual channel; cell line based; doxorubicin resistance; Human osteosarcoma cell line

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METTL1/WDR4-mediated tRNA m7G modification and mRNA translation control promotes oncogenesis and doxorubicin resistance in osteosarcoma

Project description:Osteosarcoma is the most common bone tumor that leads to high mortality in adolescents and children. The tRNA N7-methylguanosine methyltransferase METTL1 is located in chromosome 12q14.1, a region that is frequently amplified in osteosarcoma patients, while its functions and underlying mechanisms in regulation of osteosarcoma remain unknown. Herein we show that METTL1 and WDR4 are overexpressed in osteosarcoma and associated with poor patient prognosis. Knockdown of METTL1 or WDR4 causes decreased tRNA m7G modification level and impairs osteosarcoma progression in vitro and in vivo. Conversely, METTL1/WDR4 overexpression promotes osteosarcoma proliferation, migration and invasion capacities. tRNA methylation and mRNA translation profiling indicated that METTL1/WDR4 modified tRNAs enhance translation of mRNAs with more m7G tRNA-decoded codons, including extracellular matrix (ECM) remodeling effectors, which facilitates osteosarcoma progression and chemoresistance to doxorubicin.Our study demonstrates METTL1/WDR4 mediated tRNA m7G modification plays crucial oncogenic functions to enhance osteosarcoma progression and chemoresistance to doxorubicin via alteration of oncogenic mRNA translation, suggesting METTL1 inhibition combined with chemotherapy is a promising strategy for treatment of osteosarcoma patients.

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Presence of chemotherapy-induced toxicity predicts improved survival in patients with localised extremity osteosarcoma treated with doxorubicin and cisplatin: a report from the European Osteosarcoma Intergroup.

Project description:AimChemotherapy-induced toxicity is an independent prognostic indicator in several cancers. We aimed to determine whether toxicity was related to survival and histological response in high-grade localised extremity osteosarcoma. We undertook a retrospective analysis of patients treated within three consecutive randomised controlled trials (RCTs) of the European Osteosarcoma Intergroup.MethodsBetween 1982 and 2002, 533 patients were randomised to six cycles of doxorubicin 75 mg/m(2) and cisplatin 100 mg/m(2). Toxicity data were collected prospectively and graded according to the World Health Organisation (WHO) criteria. Standard univariate and multivariate models were constructed to examine the relationship between reported toxicity, survival, and histological response.ResultsFive- and 10-year overall survival was 57% (95% confidence interval (CI) 52-61%) and 53% (49-58%), respectively. Grades 3-4 oral mucositis (hazard ratio (HR) 0.51, 95% CI 0.29-0.91), grades 1-2 nausea/vomiting (HR 0.37, 95% CI 0.16-0.85), grades 1-2 thrombocytopenia (HR 0.49, 95% CI 0.27-0.87), good histological response (HR 0.42, 95% CI 0.27-0.65), and distal tumour site (HR 0.45, 95% CI 0.28-0.71) were associated with improved survival in multivariate analysis. The only factors that were independently associated with histological response were older age (odds ratio (OR) 0.18, 95% CI 0.04-0.72) and chondroblastic tumour (OR 0.28, 95% CI 0.10-0.77), both being associated with a significantly lower chance of achieving a good response.ConclusionChemotherapy-induced toxicity predicts survival in patients with localised extremity osteosarcoma. Investigation of the pharmacogenomic mechanisms of constitutional chemosensitivity underlying these observations will present opportunities for personalising treatment and could lead to improved outcomes.

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