Browsing by Subject "Head and neck squamous cell carcinoma"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Characterization of tumor immune microenvironment and cancer therapy for head and neck squamous cell carcinoma through identification of a genomic instability-related lncRNA prognostic signature
    (Frontiers Media, 2022-08-29) Jing, Lijun; Du, Yabing; Fu, Denggang; Medicine, School of Medicine
    Head and neck squamous cell carcinoma (HNSCC) represents one of the most prevalent and malignant tumors of epithelial origins with unfavorable outcomes. Increasing evidence has shown that dysregulated long non-coding RNAs (lncRNAs) correlate with tumorigenesis and genomic instability (GI), while the roles of GI-related lncRNAs in the tumor immune microenvironment (TIME) and predicting cancer therapy are still yet to be clarified. In this study, transcriptome and somatic mutation profiles with clinical parameters were obtained from the TCGA database. Patients were classified into GI-like and genomic stable (GS)-like groups according to the top 25% and bottom 25% cumulative counts of somatic mutations. Differentially expressed lncRNAs (DElncRNAs) between GI- and GS-like groups were identified as GI-related lncRNAs. These lncRNA-related coding genes were enriched in cancer-related KEGG pathways. Patients totaling 499 with clinical information were randomly divided into the training and validation sets. A total of 18 DElncRNAs screened by univariate Cox regression analysis were associated with overall survival (OS) in the training set. A GI-related lncRNA signature that comprised 10 DElncRNAs was generated through least absolute shrinkage and selection operator (Lasso)-Cox regression analysis. Patients in the high-risk group have significantly decreased OS vs. patients in the low-risk group, which was verified in internal validation and entire HNSCC sets. Integrated HNSCC sets from GEO confirmed the notable survival stratification of the signature. The time-dependent receiver operating characteristic curve demonstrated that the signature was reliable. In addition, the signature retained a strong performance of OS prediction for patients with various clinicopathological features. Cell composition analysis showed high anti-tumor immunity in the low-risk group which was evidenced by increased infiltrating CD8+ T cells and natural killer cells and reduced cancer-associated fibroblasts, which was convinced by immune signatures analysis via ssGSEA algorithm. T helper/IFNγ signaling, co-stimulatory, and co-inhibitory signatures showed increased expression in the low-risk group. Low-risk patients were predicted to be beneficial to immunotherapy, which was confirmed by patients with progressive disease who had high risk scores vs. complete remission patients. Furthermore, the drugs that might be sensitive to HNSCC were identified. In summary, the novel prognostic GILncRNA signature provided a promising approach for characterizing the TIME and predicting therapeutic strategies for HNSCC patients.
  • Thumbnail Image
    Item
    High Expression of NFX1-123 in HPV Positive Head and Neck Squamous Cell Carcinomas
    (Wiley, 2022) Chintala, Sreenivasulu; Quist, Kevin M.; Gonzalez-DeWhitt, Patricia A.; Katzenellenbogen, Rachel A.; Pediatrics, School of Medicine
    Background: High-risk human papillomaviruses (HR HPV) cause nearly all cervical cancers and, in the United States, the majority of head and neck cancers (HNSCCs). NFX1-123 is overexpressed in cervical cancers, and NFX1-123 partners with the HR HPV type 16 E6 oncoprotein to affect multiple growth, differentiation, and immune response genes. However, neither the expression of NFX1-123 nor the levels of these genes have been investigated in HPV positive (HPV+) or negative (HPV-) HNSCCs. Methods: The Cancer Genome Atlas Splicing Variants Database and HNSCC cell lines were used to quantify expression of NFX1-123 and cellular genes increased in cervical cancers. Results: NFX1-123 was increased in HPV+ HNSCCs compared to HPV- HNSCCs. LCE1B, KRT16, SPRR2G, and FBN2 were highly expressed in HNSCCs compared to normal tissues. Notch1 and CCNB1IP1 had greater expression in HPV+ HNSCCs compared to HPV- HNSCCs. Conclusion: NFX1-123 and a subset of its known targets were increased in HPV+ HNSCCs.
  • Thumbnail Image
    Item
    Human Papillomavirus Oral- and Sero- Positivity in Fanconi Anemia
    (MDPI, 2021-03-18) Sauter, Sharon L.; Zhang, Xue; Romick-Rosendale, Lindsey; Wells, Susanne I.; Myers, Kasiani C.; Brusadelli, Marion G.; Poff, Charles B.; Brown, Darron R.; Panicker, Gitika; Unger, Elizabeth R.; Mehta, Parinda A.; Bleesing, Jack; Davies, Stella M.; Butsch Kovacic, Melinda; Medicine, School of Medicine
    High-risk human papillomavirus (HPV) is prevalent and known to cause 5% of all cancers worldwide. The rare, cancer prone Fanconi anemia (FA) population is characterized by a predisposition to both head and neck squamous cell carcinomas and gynecological cancers, but the role of HPV in these cancers remains unclear. Prompted by a patient-family advocacy organization, oral HPV and HPV serological studies were simultaneously undertaken. Oral DNA samples from 201 individuals with FA, 303 unaffected family members, and 107 unrelated controls were tested for 37 HPV types. Serum samples from 115 individuals with FA and 55 unrelated controls were tested for antibodies against 9 HPV types. Oral HPV prevalence was higher for individuals with FA (20%) versus their parents (13%; p = 0.07), siblings (8%, p = 0.01), and unrelated controls (6%, p ≤ 0.001). A FA diagnosis increased HPV positivity 4.84-fold (95% CI: 1.96-11.93) in adjusted models compared to unrelated controls. Common risk factors associated with HPV in the general population did not predict oral positivity in FA, unlike unrelated controls. Seropositivity and anti-HPV titers did not significantly differ in FA versus unrelated controls regardless of HPV vaccination status. We conclude that individuals with FA are uniquely susceptible to oral HPV independent of conventional risk factors.
  • Thumbnail Image
    Item
    Oral human papillomavirus is common in individuals with Fanconi anemia
    (American Association for Cancer Research, 2015-05) Sauter, Sharon L.; Wells, Susanne I.; Zhang, Xue; Hoskins, Elizabeth E.; Davies, Stella M.; Myers, Kasiani C.; Mueller, Robin; Panicker, Gitika; Unger, Elizabeth R.; Sivaprasad, Umasundari; Brown, Darron R.; Mehta, Parinda A.; Kovacic, Melinda Butsch; Department of Microbiology & Immunology, IU School of Medicine
    Fanconi anemia is a rare genetic disorder resulting in a loss of function of the Fanconi anemia-related DNA repair pathway. Individuals with Fanconi anemia are predisposed to some cancers, including oropharyngeal and gynecologic cancers, with known associations with human papillomavirus (HPV) in the general population. As individuals with Fanconi anemia respond poorly to chemotherapy and radiation, prevention of cancer is critical. METHODS: To determine whether individuals with Fanconi anemia are particularly susceptible to oral HPV infection, we analyzed survey-based risk factor data and tested DNA isolated from oral rinses from 126 individuals with Fanconi anemia and 162 unaffected first-degree family members for 37 HPV types. RESULTS: Fourteen individuals (11.1%) with Fanconi anemia tested positive, significantly more (P = 0.003) than family members (2.5%). While HPV prevalence was even higher for sexually active individuals with Fanconi anemia (17.7% vs. 2.4% in family; P = 0.003), HPV positivity also tended to be higher in the sexually inactive (8.7% in Fanconi anemia vs. 2.9% in siblings). Indeed, having Fanconi anemia increased HPV positivity 4.9-fold (95% CI, 1.6-15.4) considering age and sexual experience, but did not differ by other potential risk factors. CONCLUSION: Our studies suggest that oral HPV is more common in individuals with Fanconi anemia. It will be essential to continue to explore associations between risk factors and immune dysfunction on HPV incidence and persistence over time. IMPACT: HPV vaccination should be emphasized in those with Fanconi anemia as a first step to prevent oropharyngeal cancers, although additional studies are needed to determine whether the level of protection it offers in this population is adequate.