Analytical performance of OncoPrism-HNSCC, an RNA-based assay to inform immune checkpoint inhibitor treatment decisions for recurrent/metastatic head and neck squamous cell carcinoma
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ABSTRACT:
PROVIDER: PRJNA1124904 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29435100.fastq.gz | Fastqsanger.gz | |||
| SRR29435200.fastq.gz | Fastqsanger.gz | |||
| SRR29435300.fastq.gz | Fastqsanger.gz | |||
| SRR29435400.fastq.gz | Fastqsanger.gz | |||
| SRR29435101.fastq.gz | Fastqsanger.gz |
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Project description:While immune checkpoint inhibitor (ICI) therapies can significantly improve outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC), only about 15–20% benefit from such treatments. Clinical tests that guide the use of ICIs are therefore critically needed. OncoPrism-HNSCC was developed to address this need. The assay combines next generation RNA sequencing-based immunomodulatory gene expression signatures with machine learning algorithms to generate an OncoPrism Score that classifies patients as having low, medium, or high likelihood of disease control in response to ICI treatment. Also, OncoPrism-HNSCC leverages the same FFPE patient tumor RNA used for ICI response prediction to identify rare cases where oncogenic rearrangements in NTRK1/2/3 or ALK genes, which may indicate the use of potentially highly effective targeted therapies. The clinical performance of OncoPrism-HNSCC has been validated. Here, we report its analytical performance in the presence of potentially confounding sources of variation.
2024-09-02 | GSE270047 | GEO
Project description:BackgroundWhile immune checkpoint inhibitor (ICI) therapies can significantly improve outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC), only about 15-20% benefit from such treatments. Clinical tests that guide the use of ICIs are therefore critically needed. OncoPrism-HNSCC was developed to address this need. The assay combines next generation RNA sequencing-based immunomodulatory gene expression signatures with machine learning algorithms to generate an OncoPrism score that classifies patients as having low, medium, or high likelihood of disease control in response to ICI treatment. Also, OncoPrism-HNSCC leverages the same FFPE patient tumor RNA used for ICI response prediction to identify rare cases where oncogenic rearrangements in NTRK1/2/3 or ALK genes may occur, and which may indicate the use of potentially highly effective targeted therapies. The clinical performance of OncoPrism-HNSCC has been validated. Here, we report its analytical performance in the presence of potentially confounding sources of variation.MethodsThe assay's analytical sensitivity was assessed by varying RNA input quantity and quality, observing the effect on ICI response prediction scores. Analytical specificity was tested by spiking increasing percentages of genomic DNA into input RNA. Intra-assay and inter-assay precision were evaluated, and the analytical sensitivity, specificity, and precision of gene fusion detection were assessed. Concordance with orthogonal methods of gene fusion detection was tested on 67 FFPE clinical samples.ResultsVarying RNA inputs as low as four-fold below the nominal input amount had little effect on ICI response prediction scores. RNA quality levels below the test threshold had no significant effect. Genomic DNA spike-ins up to 30% had only a small effect on scores. The pooled standard deviation for multiple operators, reagent lots, batches, and sequencers yielded an overall variance represented by just 0.87% of the score range of the test (0-100). NTRK and ALK gene fusion detection was 100% concordant with orthogonal methods.ConclusionsRobust and reliable analytical performance of the OncoPrism-HNSCC assay supports its clinical use, even in the presence of variation typically encountered in the laboratory setting.
| S-EPMC11705923 | biostudies-literature
Project description:Biospecimen Pre-analytical Variables (BPV)
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Project description:Biospecimen Pre-analytical Variables (BPV)
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Project description:Despite aggressive multi-modal treatment, advanced head and neck squamous cell carcinoma (HNSCC) patients are at high risk of recurrence. Matched pairs (n=38) of primary/recurrent tumors were subjected to whole exome and RNA sequencing. Mutational landscapes and genomic copy number alterations indicated diverging clonal origins in a subset of cases. Transcriptional subtyping (classical/CL, basal/BA, inflamed-mesenchymal/IMS) in primary and recurrent HNSCC (n=112) revealed more frequent CL and IMS in primary tumors with low recurrence rates and a prevalence of BA in recurrent tumors associated with p-EMT and early recurrence. 44% of matched cases underwent a subtype change from primary to recurrent tumors, preferably from IMS to BA or CL. In recurrences, HYPOXIA, P-EMT and RADIATION RESISTANCE signatures were up- and TUMOR INFLAMMATION down-regulated compared to index tumors. A therapy-induced selection of transcriptional subtypes demonstrates the importance of molecular characterization of recurrences for second-line therapy decisions to enable optimally tailored treatments.
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Project description:The NFE2L2/NRF2 oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry (MS)-based targeted proteomics assay based on internal standard triggered parallel reaction monitoring (IS-PRM) to quantify 69 NRF2 pathway components and targets as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved the existing IS-PRM acquisition algorithm, called SureQuantTM, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded (FFPE) HNSCCs, NRF2 signaling intensity positively correlated with NRF2 activating mutations and with SOX2 protein expression. PD-L2/CD273 and protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus (HPV) infection status. p16/CDKN2A protein expression positively correlated with the HPV oncogenic E7 protein, and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or FFPE archived tissues in under 90 minutes.
2023-06-08 | PXD041163 | Pride
Project description:The NFE2L2/NRF2 oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry (MS)-based targeted proteomics assay based on internal standard triggered parallel reaction monitoring (IS-PRM) to quantify 69 NRF2 pathway components and targets as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved the existing IS-PRM acquisition algorithm, called SureQuantTM, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded (FFPE) HNSCCs, NRF2 signaling intensity positively correlated with NRF2 activating mutations and with SOX2 protein expression. PD-L2/CD273 and protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus (HPV) infection status. p16/CDKN2A protein expression positively correlated with the HPV oncogenic E7 protein, and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or FFPE archived tissues in under 90 minutes.
2023-06-08 | PXD041162 | Pride
Project description:The NFE2L2/NRF2 oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry (MS)-based targeted proteomics assay based on internal standard triggered parallel reaction monitoring (IS-PRM) to quantify 69 NRF2 pathway components and targets as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved the existing IS-PRM acquisition algorithm, called SureQuantTM, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded (FFPE) HNSCCs, NRF2 signaling intensity positively correlated with NRF2 activating mutations and with SOX2 protein expression. PD-L2/CD273 and protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus (HPV) infection status. p16/CDKN2A protein expression positively correlated with the HPV oncogenic E7 protein, and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or FFPE archived tissues in under 90 minutes.
2023-06-13 | PXD042949 | Pride
Project description:The methylation analysis of HPV+ HNSCC cell lines and HPV- HNSCC cell lines as well as clones from an infected HPV- cell line by Infinium HumanMethylation450 BeadChip Analysis of 24 450k methylation profiles, comprising 3 HPV+ HNSCC cell lines and 3 HPV- HNSCC cell lines (in duplicate each) and 12 infected HPV- HNSCC cell line clones
2012-11-30 | E-GEOD-38270 | biostudies-arrayexpress
Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with significant morbidity and mortality and frequent recurrence. Pre-NGS efforts to transcriptionally classify HNSCC into groups of varying prognosis have identified four accepted molecular subtypes of disease: Atypical (AT), Basal (BA), Classical (CL), and Mesenchymal (MS). Here, we investigated the active enhancer landscapes of these subtypes using representative HNSCC cell lines and identified samples belonging to the AT subtype as having increased enhancer activity compared to the other 3 HNSCC subtypes. Cell lines belonging to atypical subtype were more resistant to bromodomain inhibitors (BETi). PRO-Seq experiments that both TCGA tumors and AT cell lines showed higher eRNA transcripts for enhancers controlling BETi resistance pathways, such as lipid metabolism and MAPK signaling. Additionally, HiChIP experiments suggested higher enhancer-promoter (E-P) contacts in the AT subtype, including on genes identified in the eRNA analysis. Consistently, known BETi resistance pathways were upregulated upon exposure to these inhibitors. Together, our results identify that the AT subtype of HNSCC is associated with high enhancer activity, resistance to BET inhibition, and signaling pathways that could serve as future targets for sensitizing HNSCC to BET inhibition.
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