Relation of a Hypoxia Metagene Derived from Head and Neck Cancer to Prognosis of Multiple Cancers

Winter, Stuart C; Buffa, Francesca M.; Silva, Priyamal; Miller, Crispin; Valentine, Helen; Turley, Helen; Shah, Ketan; Cox, Graham J.; Corbridge, Rogan; Homer, Jarrod J; Musgrove, Brian; Slevin, Nicholas J; Sloan, Philip; Price, Patricia M; West, Catharine M L; Harris, Adrian L.

doi:10.1158/0008-5472.can-06-3322

Cited by 342 publications

(370 citation statements)

References 39 publications

(60 reference statements)

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“…Ethical approval was obtained from the local research ethics committees (Oxford and South Manchester). Full patient demographics are provided in Table 1 and Winter et al 7 All patients underwent surgical resection with curative intent. Postoperative radiotherapy was given to all but 5 patients, either because it was not indicated or because the patient declined.…”

Section: Clinical Samplesmentioning

confidence: 99%

“…CA9 immunohistochemistry has been described previously, 29 and details of antibodies and the scoring system are given in Winter et al 7 Briefly, a mouse monoclonal antihuman antibody raised to the external domain of CA9 (a gift from Profs. S. Pastorekova and J. Pastorek) and ESEE122, a mouse monoclonal immunoglobulin G1 antibody to human HIF-1alpha (University of Oxford, Oxford, UK) were used and scored as continuous variables by 2 observers.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Expression values for the genes containing the microRNA precursors and hypoxia-related genes were determined from Affymetrix GeneChips in the published datasets of Winter et al 7 and Rickman et al 30 Data were preprocessed and normalized as previously described. 7 A published 99-gene hypoxia up-regulated metagene was used that has been derived in HNSCC from genes clustering with known hypoxia-regulated genes.…”

Section: Microarray Datamentioning

confidence: 99%

“…7 A published 99-gene hypoxia up-regulated metagene was used that has been derived in HNSCC from genes clustering with known hypoxia-regulated genes. 7 A continuous hypoxia score was derived from the metagene to rank the tumors from least to most hypoxic.…”

Section: Microarray Datamentioning

confidence: 99%

“…The median RNA expression of the 99 genes in the signature was an independent prognostic factor for recurrence-free survival in HNSCC. 7 Similarly, a gene-expression signature of the cellular response to hypoxia was associated with a significantly poorer prognosis in breast and ovarian cancer. 8 Gene sets can also be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC.…”

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confidence: 99%

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hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

Gee

Camps

Buffa

et al. 2010

Cancer

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224

157

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BACKGROUND:Hypoxia is an important mechanism of treatment resistance in head and neck squamous cell carcinoma (HNSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The authors have investigated the role of 3 microRNAs, including the hypoxia-induced hsa-miR-210, as potential markers of hypoxia or prognosis. METHODS: Three hypoxia-related microRNAs, hsa-miR-210, hsa-miR-21, and hsa-miR-10b, were measured in 46 samples from patients with HNSCC. Expression levels were correlated with clinicopathological variables and other markers of hypoxia: a published 99-gene hypoxia metagene, individual hypoxia-related genes such as TWIST1, and immunohistochemical expression of hypoxia-inducible factor 1 and its target gene carbonic anhydrase 9. We then performed survival analyses to investigate the prognostic significance of these microRNAs. RESULTS: Only the level of hsa-miR-210 was significantly correlated with other markers of hypoxia, including the 99-gene hypoxia metagene (rho ¼ 0.67, P < .001). We found no association between hsa-miR-210, hsamiR-21, or hsa-miR-10b and clinicopathological variables such as tumor size, differentiation, and stage. However, high levels of hsa-miR-210 were associated with locoregional disease recurrence (P ¼ .001) and short overall survival (P ¼ .008). hsa-miR-21 and hsa-miR-10b had no prognostic significance. CONCLUSIONS: Expression of hsa-miR-210 in head and neck cancer correlates with other approaches for assessing hypoxia and is associated with prognosis. This warrants further study as a classification marker of patients for therapies involving modulation of hypoxia.

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Section: Clinical Samplesmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: Microarray Datamentioning

confidence: 99%

Section: Microarray Datamentioning

confidence: 99%

mentioning

confidence: 99%

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hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

Gee

Camps

Buffa

et al. 2010

Cancer

Self Cite

224

157

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Identification and validation of a combined hypoxia and immune index for triple‐negative breast cancer

et al. 2020

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The interaction between hypoxia and immune status has been confirmed in various cancer settings, and corresponding treatments have been investigated. However, reliable biomarkers are needed for individual treatment, so we sought to develop a novel scoring system based on hypoxia and immune status. Prognostic hypoxia-immune status-related signatures of patients with triple-negative breast cancer (TNBC) were identified in The Cancer Genome Atlas (TCGA) (N = 158), Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), and GSE58812 (N = 107). LASSO Cox regression was used for model construction. Hypoxia and immune status expression profiles were analyzed, and infiltrating immune cells were compared. Quantitative real-time PCR (qRT-PCR) was used for validation in the Sun Yat-sen University Cancer Center (SYSUCC) cohort, and immunofluorescence was applied for the detection of hypoxia and immune markers in cancer tissues. Ten cross-cohort prognostic hypoxia-immune signatures were included to construct the comprehensive index of hypoxia and immune (CIHI) in the METABRIC cohort. Two subgroups of patients with distinct hypoxia-immune status conditions were identified using CIHI: hypoxia high /immune low and hypoxia low /immune high , with a significantly better overall survival (OS) rate in the latter (P < 0.01). The prognostic value of CIHI was further validated in the TCGA, GSE58812, and SYSUCC cohorts (P < 0.01).

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Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models

Lee,

Singleton,

Harms

et al. 2024

Molecular Oncology

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Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model tumour hypoxia. We established 20 patient‐derived xenograft (PDX) and cell line‐derived xenograft (CDX) models of HNSCC that we characterised for their fidelity to represent clinical HNSCC in gene expression, hypoxia status and proliferation and that were evaluated for their sensitivity to hypoxia‐activated prodrugs (HAPs). PDX models showed greater fidelity in gene expression to clinical HNSCC than cell lines, as did CDX models relative to their paired cell lines. PDX models were significantly more hypoxic than CDX models, as assessed by hypoxia gene signatures and pimonidazole immunohistochemistry, and showed similar hypoxia gene expression to clinical HNSCC tumours. Hypoxia or proliferation status alone could not determine HAP sensitivity across our 20 HNSCC and two non‐HNSCC tumour models by either tumour growth inhibition or killing of hypoxia cells in an ex vivo clonogenic assay. In summary, our tumour models provide clinically relevant HNSCC models that are suitable for evaluating hypoxia‐targeting therapies; however, additional biomarkers to hypoxia are required to accurately predict drug sensitivity.

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Relation of a Hypoxia Metagene Derived from Head and Neck Cancer to Prognosis of Multiple Cancers

Cited by 342 publications

References 39 publications

hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

Identification and validation of a combined hypoxia and immune index for triple‐negative breast cancer

Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models

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