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A Systematic Review of the Heterogenous Gene Expression Patterns Associated with Multidrug Chemoresistance in
Phakamani Goodman Mthethwa1, Leonard Charles Marais2, Veron Ramsuran3
1Department of Orthopaedic Surgery, Dr. Pixley Ka Isaka Seme Memorial Hospital, University of KwaZulu-Natal, 310 Bhejane Street, KwaMashu, Durban 4360, South Africa.
Abstract:
Multidrug chemoresistance (MDR) remains the most significant obstacle to improving survival in osteosarcoma patients. Heterogeneous genetic alterations characterise the tumour microenvironment, and host molecular markers have been associated with MDR. This systematic review examines the genetic alterations of molecular biomarkers associated with multidrug chemotherapy resistance in genome-wide analysis of central high-grade conventional osteosarcoma (COS). We systematically searched MEDLINE, EMBASE, Web of Science, Wiley online library and Scopus. Only human studies involving genome-wide analysis were included, while candidate gene, in vitro and animal studies were excluded. The risk of bias of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. The systematic search identified 1355 records. Following the screening, six studies were included in the qualitative analysis. There were 473 differentially expressed genes (DEGs) associated with chemotherapy response in COS. Fifty-seven of those were associated with MDR in osteosarcoma. The heterogeneous gene expressions were related to the mechanism of MDR in osteosarcoma. The mechanisms include drug-related sensitivity genes, bone remodelling and signal transduction. Complex, variable and heterogenous gene expression patterns underpin MDR in osteosarcoma. Further research is needed to identify the most relevant alterations for prognostication and to guide the development of possible therapeutic targets.
Insights
Multidrug chemoresistance (MDR) in osteosarcoma is a major challenge. This review found complex gene expression patterns linked to MDR, highlighting the need for new therapeutic targets.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Multidrug chemoresistance (MDR) significantly hinders survival rates for osteosarcoma patients.
- Tumor microenvironment heterogeneity and host molecular markers are implicated in MDR development.
- Identifying genetic drivers of MDR is crucial for improving treatment outcomes in conventional osteosarcoma (COS).
Approach:
- A systematic review was conducted, searching major scientific databases (MEDLINE, EMBASE, Web of Science, Scopus, Wiley online library).
- Included studies focused exclusively on human genome-wide analyses of high-grade conventional osteosarcoma (COS).
- Excluded were candidate gene, in vitro, and animal studies to ensure relevance and quality.
Key Points:
- Six studies met the inclusion criteria, analyzing 473 differentially expressed genes (DEGs) related to chemotherapy response in COS.
- Fifty-seven DEGs were specifically associated with MDR in osteosarcoma.
- Identified mechanisms of MDR include drug sensitivity genes, bone remodeling pathways, and signal transduction.
Conclusions:
- Osteosarcoma MDR is driven by complex, variable, and heterogeneous gene expression patterns.
- Further research is essential to pinpoint key genetic alterations for prognostication.
- Identifying these alterations will guide the development of novel therapeutic strategies against osteosarcoma MDR.
