Impact of hypoxia on cervical cancer outcomes

Objectives: Oxygen-enhanced MRI (OE-MRI) or tissue oxygen-level dependent (TOLD) MRI is an imaging technique under investigation for its ability to quantify and map oxygen distributions within tumours. The aim of this study was to identify and characterise the research into OE-MRI for characterising hypoxia in solid tumours. Methods: A scoping review of published literature was performed on the PubMed and Web of Science databases for articles published before 27th May 2022. Studies imaging solid tumours using proton-MRI to measure oxygen induced T1/R1 relaxation time/rate changes were included. Grey literature was searched from conference abstracts and active clinical trials. Results: 49 unique records met the inclusion criteria consisting of 34 journal articles and 15 conference abstracts. The majority of articles were pre-clinical studies (31 articles) with 15 human only studies. Pre-clinical studies in a range of tumour types demonstrated consistent correlation of OE-MRI with alternative hypoxia measurements. No clear consensus on optimal acquisition technique or analysis methodology was found. No prospective, adequately powered, multicentre clinical studies relating OE-MRI hypoxia markers to patient outcomes were identified. Conclusions: There is good preclinical evidence of the utility of OE-MRI in tumour hypoxia assessment however there are significant gaps in clinical research that need to be addressed to develop OE-MRI into a clinically applicable tumour hypoxia imaging technique. Advances in knowledge: The evidence base of OE-MRI in tumour hypoxia assessment is presented along with a summary of the research gaps to be addressed to transform OE-MRI derived parameters into tumour hypoxia biomarkers.

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“…gov website. [7][8][9] All of these studies have corresponding conference abstracts included in the final search results. [10][11][12]…”

Section: Resultsmentioning

confidence: 99%

T₁ based oxygen-enhanced MRI in tumours; a scoping review of current research

McCabe

Martin

Shah

et al. 2023

BJR

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“…Extrinsic abnormalities of tumor microenvironment, particularly tumor hypoxia, reduce the efficacy of radiotherapy, shorten survival time, and increase recurrences [ 5 ]. A recent review article summarized hypoxia-targeted strategies and identified further research and new treatment paradigms needed to improve patient outcomes [ 6 ]. Hypoxia-inducible factor (HIF) is a transcriptional activator of various genes related to cellular adaptive responses to hypoxia.…”

Section: Introductionmentioning

confidence: 99%

HIF-3α-Induced miR-630 Expression Promotes Cancer Hallmarks in Cervical Cancer Cells by Forming a Positive Feedback Loop

Gao

Ren

Jiao

et al. 2022

Journal of Immunology Research

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Purpose. Hypoxia has crucial functions in the development and metastasis of cervical cancer by inducing the expression of numerous genes, including microRNA genes. But we know little about how the hypoxia factors and microRNAs orchestrate to regulate hallmarks of cervical cancer cells. Methods. We conducted RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) experiments to investigate the targets of HIF-3α or miR-630. ChIP-qPCR and RT-qPCR were carried out to validate the results of ChIP-seq and RNA-seq. Cellular, molecular, and radiation experiments were conducted to explore the functions of miR-630. Results. In this study, we showed that hypoxia-induced overexpression of HIF-3α increased the expression of dozens of miRNAs, including miR-630. Hypoxia could also directly induce miR-630 expression. ChIP-seq data showed that HIF-3α activates miR-630 expression by directly binding to the promoter of its host gene. Meanwhile, stable overexpression of miR-630 increased the expression of HIF-3α, but repressed the expression of HIF-1α, indicating a positive feedback loop between HIF-3α and miR-630. Consequently, stable overexpression of miR-630 in HeLa cells promotes cancer hallmarks, including radioresistance, inhibition of apoptosis, increased migration and invasion, and EMT-mediated metastasis. Meanwhile, inhibition of miR-630 showed opposite features. Conclusion. Taken together, our findings indicate a novel hypoxia-induced HIF-3α and miR-630 regulatory feedback loop contributing to metastasis and progression of cervical cancer cells and suggest that HIF-3α and miR-630 might act as potential biomarkers and therapeutic targets for cervical cancer in the future.

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“…In 2018, there were about 569,000 confirmed cases of CC and about 311,000 deaths worldwide (1). Approximately 85% of de aths from CC occur in underdeveloped countries and areas (2), with the highest mortality rates found in parts of America and sub-Saharan Africa (3).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analyses identify RIPOR2 as a genomic instability-associated immune prognostic biomarker in cervical cancer

Zou

Gao

et al. 2022

Front. Immunol.

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Cervical cancer (CC) is a malignancy that tends to have a poor prognosis when detected at an advanced stage; however, there are few studies on the early detection of CC at the genetic level. The tumor microenvironment (TME) and genomic instability (GI) greatly affect the survival of tumor patients via effects on carcinogenesis, tumor growth, and resistance. It is necessary to identify biomarkers simultaneously correlated with components of the TME and with GI, as these could predict the survival of patients and the efficacy of immunotherapy. In this study, we extracted somatic mutational data and transcriptome information of CC cases from The Cancer Genome Atlas, and the GSE44001 dataset from the Gene Expression Omnibus database was downloaded for external verification. Stromal components differed most between genomic unstable and genomic stable groups. Differentially expressed genes were screened out on the basis of GI and StromalScore, using somatic mutation information and ESTIMATE methods. We obtained the intersection of GI- and StromalScore-related genes and used them to establish a four-gene signature comprising RIPOR2, CCL22, PAMR1, and FBN1 for prognostic prediction. We described immunogenomic characteristics using this risk model, with methods including CIBERSORT, gene set enrichment analysis (GSEA), and single-sample GSEA. We further explored the protective factor RIPOR2, which has a close relationship with ImmuneScore. A series of in vitro experiments, including immunohistochemistry, immunofluorescence, quantitative reverse transcription PCR, transwell assay, CCK8 assay, EdU assay, cell cycle detection, colony formation assay, and Western blotting were performed to validate RIPOR2 as an anti-tumor signature. Combined with integrative bioinformatic analyses, these experiments showed a strong relationship between RIPOR2 with tumor mutation burden, expression of genes related to DNA damage response (especially PARP1), TME-related scores, activation of immune checkpoint activation, and efficacy of immunotherapy. To summarize, RIPOR2 was successfully identified through comprehensive analyses of the TME and GI as a potential biomarker for forecasting the prognosis and immunotherapy response, which could guide clinical strategies for the treatment of CC patients.

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Impact of hypoxia on cervical cancer outcomes

Cited by 28 publications

References 102 publications

T₁ based oxygen-enhanced MRI in tumours; a scoping review of current research

T₁ based oxygen-enhanced MRI in tumours; a scoping review of current research

HIF-3α-Induced miR-630 Expression Promotes Cancer Hallmarks in Cervical Cancer Cells by Forming a Positive Feedback Loop

Comprehensive analyses identify RIPOR2 as a genomic instability-associated immune prognostic biomarker in cervical cancer

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Impact of hypoxia on cervical cancer outcomes

Cited by 28 publications

References 102 publications

T1 based oxygen-enhanced MRI in tumours; a scoping review of current research

T1 based oxygen-enhanced MRI in tumours; a scoping review of current research

HIF-3α-Induced miR-630 Expression Promotes Cancer Hallmarks in Cervical Cancer Cells by Forming a Positive Feedback Loop

Comprehensive analyses identify RIPOR2 as a genomic instability-associated immune prognostic biomarker in cervical cancer

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T₁ based oxygen-enhanced MRI in tumours; a scoping review of current research

T₁ based oxygen-enhanced MRI in tumours; a scoping review of current research