Gene expression characterization of HPV positive head and neck cancer to predict response to Chemoradiation
Ontology highlight
ABSTRACT: Background: Human papillomavirus has been shown to have a causal role in the development of head and neck squamous cell carcinoma and represents a distinct and well-defined pathology. While HPV-positive HNSCC is associated with a better response to treatment and prognosis, a subset of patients do not respond favorably to current standard of care thus suffering unnecessary morbidity and delay to receive effective therapy. Methods: RNA from nineteen patients with HPV-positive HNSCC was subjected to gene expression analysis using Affymetrix microarrays. HPV-status was confirmed by detection of HPV16 E7 with RT-PCR. Results: In addition to specific genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes were highly represented in the cell processes of genomic stability, cell cycle, and DNA damage. Conclusions: This pilot study suggests possible biomarkers that predict response to chemoradiation therapy. These data can potentially lead to an assay that can be used clinically to predict HPV-positive HNSCC patients that will not benefit from chemoradiation, thus helping clinicians to lower morbidity and get selected patients to surgery faster.
Project description:Background: Human papillomavirus has been shown to have a causal role in the development of head and neck squamous cell carcinoma and represents a distinct and well-defined pathology. While HPV-positive HNSCC is associated with a better response to treatment and prognosis, a subset of patients do not respond favorably to current standard of care thus suffering unnecessary morbidity and delay to receive effective therapy. Methods: RNA from nineteen patients with HPV-positive HNSCC was subjected to gene expression analysis using Affymetrix microarrays. HPV-status was confirmed by detection of HPV16 E7 with RT-PCR. Results: In addition to specific genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes were highly represented in the cell processes of genomic stability, cell cycle, and DNA damage. Conclusions: This pilot study suggests possible biomarkers that predict response to chemoradiation therapy. These data can potentially lead to an assay that can be used clinically to predict HPV-positive HNSCC patients that will not benefit from chemoradiation, thus helping clinicians to lower morbidity and get selected patients to surgery faster. HPV-positive head and neck squamous cell carcinoma (HNSCC) has a good prognosis with a large percentage of patients responding to therapy. However, a certain percentage of patients do not respond. Gene expression data from Affymetrix Human Exon 1.0ST microarrays was utilized to compare patients that responded to therapy with those that did not respond.
Project description:Gene expression profiling to predict outcome after chemoradiation in head and neck cancer Purpose. The goal of the present study was to improve prediction of outcome after chemoradiation in advanced head and neck cancer using gene expression analysis. Materials and Methods. We collected 92 biopsies from untreated head and neck cancer patients subsequently given cisplatin-based chemoradiation (RADPLAT) for advanced squamous cell carcinomas (HNSCC). After RNA extraction and labeling we performed dye swap experiments using 35k oligo-microarrays. Supervised analyses were performed to create classifiers to predict local control, locoregional control and disease recurrence. Published gene sets with prognostic value in other studies were also tested. Results. Using supervised classification on the whole series, gene sets separating good and poor outcome could be found for all end-points. However, when splitting tumors into training and validation groups, no robust classifiers could be found. Also previously published signatures with prognostic value have been tested. Conclusion. Gene sets can be found with predictive potential for locoregional control after combined radiation and chemotherapy in HNSCC. How treatment-specific these gene sets are needs further study.
Project description:This study performed genomic sequencing on a rare phenotype of HPV-positive oropharyngeal squamous cell carcinoma which was resistant to standard of care platinum based chemoradiation treatment. Tissue was collected from archival FFPE when available from pretreatment and post treamtent samples from four patients and these were batch corrected to be compared to known HPV-positive tumors without recurrent disease
Project description:Human papillomavirus (HPV) positive HNSCC patients generally have a favorable survival and promising responsiveness to radiotherapy, chemoradiotherapy and checkpoint blockades. However, HPV negative patients, the majority of HNSCC patients, have been largely overlooked. Cell death has been involved in the therapeutic resistance of cancers. We constructed a cell death index (CDI), based on autophagy, apoptosis and pyroptosis related genes, to predict the prognosis for HNSCC using TCGA dataset, and validated in a cohort from Qilu Hospital of Shandong University. We performed RNA sequencing of 28 paraffin-embedded tissue from HNSCC patients and determined HPV status by immunohistochemistry of p16. We found that CDI was an independent prognostic indicator for overall survival. Notably, the prognostic value of CDI was more profound in HPV negative HNSCC patients compared with those with HPV positivity.
Project description:The predictive value of microRNAs for the efficacy of chemoradiation (CRTX) in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated. Formalin-fixed, paraffin-embedded tumor material was collected from patients with locally advanced HNSCC treated within the ARO-0401 phase III trial with radiotherapy in combination with either 5-fluorouracil/cisplatin (CDDP-CRTX) or 5-fluorouracil/mitomycin C (MMC-CRTX).
Project description:Analysis of peripheral circulating mRNA expression levels in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma. The hypothesis test was that chemoradiation alters the circulating mRNA expression profiles and the profiling is predictive of pathological response. Results provide information on the response of circulating mRNAs to chemoradiation and identify novel biomarkers or targets in esophageal squamous cell carcinoma. Total RNA obtained from peripheral whole blood before and after neoadjuvant chemoradiation in patients with esophageal squamous cell carcinoma. 21 patients with 42 samples were analyzed. The expression profiles from pathological complete responders were compared to non-complete responders.
Project description:Analysis of peripheral circulating mRNA expression levels in patients undergoing neoadjuvant chemoradiation for esophageal squamous cell carcinoma. The hypothesis test was that chemoradiation alters the circulating mRNA expression profiles and the profiling is predictive of pathological response. Results provide information on the response of circulating mRNAs to chemoradiation and identify novel biomarkers or targets in esophageal squamous cell carcinoma.
Project description:The involvement of microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis, prognosis and response to therapy is becoming increasingly appreciated. The etiology of head and neck squamous cell carcinoma (HNSCC) is predominantly associated with the synergistic effects of tobacco and alcohol use, as well as Human Papilloma Virus (HPV) infection, which embodies a distinct clinical and biological phenotype. We sought to examine whether the profile of miRNAs in HNSCC varies based on HPV status, and to identify specific miRNAs altered in head and neck carcinogenesis. Total RNA was isolated from 16 HNSCC fresh frozen primary tumors, 5 fresh frozen non-diseased head and neck epithelial tissues, and 2 HNSCC cell lines. The miRNA profile of 662 individual miRNAs in these tissues was examined by microarray. 18 miRNAs are significantly altered in their expression between normal tissues and HNSCC tumors and 5 miRNAs are identified as significantly differentially expressed between HPV-positive (HPV+) and HPV-negative (HPV-) tumors. A striking difference in expression pattern of miRNA was also observed between primary tissues and cell lines. These data suggest that the pattern of miRNA expression may be reflective of disease etiology, and may be useful in the realm of diagnostic biomarkers defining broadly responsive prevention and treatment strategies for HNSCC. These data also suggest that cultured tumor cell lines may be inappropriate for novel miRNA biomarker identification. Keywords: miRNA; Disease-state analysis Expression of 662 individual miRNA was assessed in16 HNSCC fresh frozen primary tumors, 5 fresh frozen non-diseased head and neck epithelial tissues, and 2 HNSCC cell lines were arrayed
Project description:Head and neck squamous cell carcinomas (HNSCC) driven by human papillomavirus (HPV) generally have a more favourable prognosis. We hypothesized that HPV-positive HNSCC may be identified based on a miRNA signature according to their specific molecular pathogenesis and are characterized by a unique transcriptome compared to HPV-negative HNSCC. We characterized the miRNA-expression patterns of the tumors from 229 head and neck squamous cell carcinoma patients by Agilent miRNA microarrays in order to define a HPV-predicting miRNA signature.