Project description:We used RNA-seq to evaluate the transcriptomic changes induced by permanent SMYD3 KO in the HPV-negative head and neck squamous cell carcinoma cell lines HN-6.
Project description:Persistent infection by high-risk human papillomaviruses (HPVs) is associated with the development of cervical cancer and a subset of anogenital and head and neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs) plays an important role in the development of cancer, including HPV-related tumors. MiRNA expression profile was investigated by microrray analysis in the HPV-positive cervical cancer cell lines SiHa (HPV16-positive cell line derived from a cervical squamous cell carcinoma), CaSki (HPV16-positive cell line derived from a metastatic cervical epidermoid carcinoma), and HeLa (HPV18-positive cell line derived from a cervical adenocarcinoma) and compared with primary HFKs and C33a (HPV-negative cervical cell line).
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.
Project description:<p>Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide(1). Various chemical carcinogens (tobacco, alcohol and betel nut), human papillomavirus (HPV) infection, and genetic predisposition contribute to the etiology of HNSCC, and to the complex genetic alterations in tumor subsets that differ in prognosis and response to therapies (2).</p> <p>Recently, a comprehensive landscape of genomic and transcriptomic alterations in HNSCC tumors has emerged from The Cancer Genome Atlas (TCGA) Network (3). TCGA revealed novel and previously recognized gene and chromosomal region copy number alterations (CNAs), mutations, and expression clusters, and defined their frequency, co-occurrence, and relationship to common and rare subtypes of HPV(-) and (+) tumors that vary in prognosis. To identify cell line models for determining the functional role and therapeutic importance of these alterations, we are performing whole exome and RNA sequencing and bioinformatic analysis of an expanded panel of 15 HPV(-) and 11 HPV(+) HNSCC cell lines and primary oral keratinocytes.</p> <p>We find that the recurrent genomic alterations in cell lines are remarkably consistent with those found in more aggressive tumors, from which cell lines have traditionally been most readily adapted to culture (4). Genome-wide correlation of CN (copy number) with expression identified a suite of potential drivers or modifier genes that differ by HPV status, and are of potential biologic and therapeutic relevance. Further, our findings elucidate and validate genomic alterations underpinning numerous discoveries made with these widely-used and recently derived HNSCC lines, and provide a roadmap for their potential use as models for future studies of tumor subtypes with worse prognosis.</p> <p>References</p> <p> <ol> <li>Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.</li> <li>Van Waes C, Musbahi O. Genomics and advances towards precision medicine for head and neck squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2017;2(5):310-9.</li> <li>Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576-82.</li> <li>White JS, Weissfeld JL, Ragin CC, Rossie KM, Martin CL, Shuster M, et al. The influence of clinical and demographic risk factors on the establishment of head and neck squamous cell carcinoma cell lines. Oral Oncol. 2007;43(7):701-12.</li> </ol> </p>
Project description:Oncogenic human papillomaviruses (HPVs) are associated with nearly all carcinomas of the uterine cervix and have also become an increasingly important factor in the etiology of a subset of oropharyngeal tumors. HPV-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. We analyzed the genome-wide expression patterns in two HPV(+) and two HPV(-) squamous cell carcinoma (SCC) cell lines.
Project description:To identify target genes of cancer-related microRNAs in human cancer, several cell lines (bladder cancer, prostate cancer, renal cell carcinoma, esophageal squamous cell carcinoma, and head and neck squamous cell carcinoma) were subjected to Agilent whole genome microarrays.
Project description:Microarrays were used to examine gene expression differences between human head and neck squamous cell carcinoma cell lines (FaDu, UTSCC8, UTSCC42a) grown in culture in comparison to a normal oral epithelial cell line. Gene expression data was integrated with global protein expression of head and neck squamous cell carcinoma cell lines and conditioned media to identify secreted protein markers up-regulated at the mRNA level in cancer cells versus the normal cell line. Total RNA obtained from head and neck squamous cell carcinoma cell lines and a normal oral epithelial cell line
Project description:Oncogenic human papillomaviruses (HPVs) are associated with nearly all carcinomas of the uterine cervix and have also become an increasingly important factor in the etiology of a subset of oropharyngeal tumors. HPV-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. We analyzed the genome-wide expression patterns in two HPV(+) and two HPV(-) squamous cell carcinoma (SCC) cell lines. The Affymetrix Human Genome U133 Plus 2.0 Array platform was used to assess genome-wide expression differences between the HPV(+) and HPV(-) cell lines utilizing the RMA normalization package available for R. Cell lines analyzed: UM-SCC-4, UM-SCC-47, UM-SCC-74A, and CaSki.
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