scholarly journals VirTect: a computational method for detecting virus species from RNA-Seq and its application in head and neck squamous cell carcinoma

2018 ◽  
Author(s):  
Atlas Khan ◽  
Qian Liu ◽  
Xuelian Chen ◽  
Yunjing Zeng ◽  
Andres Stucky ◽  
...  

AbstractNext generation sequencing (NGS) provides an opportunity to detect viral species from RNA-seq data on human tissues, but existing computational approaches do not perform optimally on clinical samples. We developed a bioinformatics method called VirTect for detecting viruses in neoplastic human tissues using RNA-seq data. Here, we used VirTect to analyze RNA-seq data from 363 HNSCC (head and neck squamous cell carcinoma) patients and identified 22 HPV-induced HNSCCs. These predictions were validated by manual review of pathology reports on histopathologic specimens. Compared to two existing prediction methods, VirusFinder and VirusSeq, VirTect demonstrated superior performance with many fewer false positives and false negatives. The majority of HPV carcinogenesis studies thus far have been performed on cervical cancer and generalized to HNSCC. Our results suggest that HPV-induced HNSCC involves unique mechanisms of carcinogenesis, so understanding these molecular mechanisms will have a significant impact on therapeutic approaches and outcomes. In summary, VirTect can be an effective solution for the detection of viruses with NGS data, and can facilitate the clinicopathologic characterization of various types of cancers with broad applications for oncology.Significance StatementWe developed a new bioinformatics tool, and reported the new inside of HPV carcinogenesis mechanism in HPV-induced head and neck squamous cell carcinoma (HNSCC). This novel bioin-formatics tool and the new knowledge of HPV-induced HNSCC will facilitate the development of target therapies for treating HNSCC.

2016 ◽  
Vol 12 (4) ◽  
pp. 2846-2853 ◽  
Author(s):  
Vicky Yu ◽  
Pranav Singh ◽  
Elham Rahimy ◽  
Hao Zheng ◽  
Selena Z. Kuo ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yoon Young Go ◽  
Su Ra Kim ◽  
Do Yeon Kim ◽  
Sung-Won Chae ◽  
Jae-Jun Song

AbstractCannabidiol (CBD) has anti-tumorigenic activity. However, the anti-cancer effect of CBD on head and neck squamous cell carcinoma (HNSCC) remains unclear. The cytotoxicity of CBD on HNSCC was analyzed using cell survival and colony-forming assays in vitro. RNA-seq was used for determining the mechanism underlying CBD-induced cell death. Xenograft mouse models were used to determine CBD’s effects in vivo. CBD treatment significantly reduced migration/invasion and viability of HNSCC cells in a dose- and time-dependent manner. HNSCC mouse xenograft models revealed anti-tumor effects of CBD. Furthermore, combinational treatment with CBD enhanced the efficacy of chemotherapy drugs. Apoptosis and autophagy processes were involved in CBD-induced cytotoxicity of HNSCCs. RNA-seq identified decreased expression of genes associated with DNA repair, cell division, and cell proliferation, which were involved in CBD-mediated cytotoxicity toward HNSCCs. We identified CBD as a new potential anti-cancer compound for single or combination therapy of HNSCC.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17534-e17534
Author(s):  
Shine-Gwo Shiah ◽  
Sung-Tau Chou ◽  
Ching-Chuan Kuo ◽  
Ya-Hui Chi

e17534 Background: Polycomb group (PcG) proteins influence the development and progression of cancer. However, the mechanism that contributes to tumorigenesis have not been fully understood in head and neck squamous cell carcinoma (HNSCC). Methods: The expression of chromobox 8 (CBX8), a member of the polycomb group (PcG) of proteins, on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-410-3p and CBX8 were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Results: Here we found that CBX8 is upregulated in HNSCC tissues and cell lines. Using CBX8 knockdown cDNA microarray, we identify a CBX8-mediated target gene MIPOL1 which is inversely correlated with CBX8 expression in HNSCC tissues. Ectopic expression of MIPOL1 could inhibit tumor invasion and migration, whereas MIPOL1 silencing suppressed these effects in CBX8-knockdown HNSCC cells. Otherwise, depletion of CBX8 also induced p53 activity and increased the expression level of p21 and p27 through MIPOL1-independent manner, which result in cell cycle arrest in G2M phase. Silencing of p53 could inhibit p21 and p27 accumulation in CBX8 knockdown cells. Furthermore, we demonstrated that down-regulation of miR-410-3p promoted HNSCC cells migration and invasion through directly targeting CBX8. Overexpression of miR-410-3p decreased CBX8 expression and reduced migration and invasion, while ectopic expression of CBX8 rescued the miR-410-3p-reduced migration and invasion. In clinical samples, miR-410-3p level closely inversely correlated with CBX8 and positively correlated with MIPOL1. Conclusions: Collectively, our findings indicate that miR-410-3p may act as a tumor suppressor via negatively regulating CBX8. The newly identified miR-410-3p/CBX8/MIPOL1 and miR-410-3p/CBX8/p53 signaling axes may suggest new therapeutic strategies against HNSCC.


2019 ◽  
Vol 13 (4) ◽  
pp. 829-839 ◽  
Author(s):  
Atlas Khan ◽  
Qian Liu ◽  
Xuelian Chen ◽  
Andres Stucky ◽  
Parish P. Sedghizadeh ◽  
...  

2016 ◽  
Vol 46 (1) ◽  
pp. 53
Author(s):  
Azwar Azwar ◽  
Sofia Mubarika ◽  
Agus Surono

Latar belakang: Karsinoma sel skuamosa kepala dan leher merupakan salah satu kanker terseringdi seluruh dunia. Pendekatan pengobatan agresif dan multidisiplin telah dilakukan, namun belum adapeningkatan yang signifikan dalam kelangsungan hidup 5 tahun, selama 20 tahun terakhir. Kegagalanpengobatan terjadi dalam bentuk kekambuhan lokoregional, metastasis jauh, dan/atau tumor primer kedua.Berbagai penanda molekular tumor telah diteliti untuk mengetahui potensinya dalam memprediksi hasilpenyakit atau respon terhadap terapi.Tujuan: Mengetahui hubungan ekspresi protein p53, Bcl-2, c-Myc,dan MMP-9 berdasarkan gambaran klinikopatologis karsinoma sel skuamosa kepala dan leher di RumahSakit dr. Zainoel Abidin.Metode: Studi menggunakan desain cross sectional. Sampel terdiri dari 60blok parafin karsinoma sel skuamosa kepala dan leher. Prosedur pewarnaan imunohistokimia dilakukandengan menggunakan antibodi monoklonal terhadap p53, Bcl-2, c-Myc, dan MMP-9. Ekspresi proteinp53, Bcl-2, c-Myc, dan MMP-9 dianalisis secara imunohistokimia pada karsinoma sel skuamosa kepaladan leher kemudian hasilnya dihubungkan dengan parameter klinikopatologis seperti usia, jenis kelamin,lokasi tumor, diferensiasi tumor, metastasis kelenjar getah bening dan stadium tumor, kemudian dianalisisstatistik dengan Chi square.Hasil: Hasil penelitian menunjukkan terdapat hubungan bermakna tingkatekspresi p53 dengan metastasis lokal (p=0,021) dan ada hubungan bermakna tingkat ekspresi MMP-9dengan lokasi tumor (p=0,026). Tidak terdapat hubungan ekspresi p53, Bcl-2, cMyc, dan MMP-9 terhadapusia, jenis kelamin, stadium tumor, diferensiasi histologi, tingkat T, N, dan metastasis jauh.Kesimpulan:Ada hubungan ekpresi p53 dengan metastasis kelenjar limfe regional dan ekspresi MMP-9 dengan lokasitumor pada karsinoma sel skuamosa kepala dan leher. Kata kunci: Karsinoma sel skuamosa kepala dan leher, p53, Bcl-2, c-Myc, MMP-9 ABSTRACTBackground: Head and neck squamous cell carcinoma (HNSCC) is one of the most commoncancers world wide. Although aggressive and multidisciplinary approach to the treatment has been done,there is no significant improvement in 5-year survival in the last 20 years. Treatment failure occurredin the form of locoregional recurrence, distant metastasis, and/or a second primary tumor. A variety oftumor molecular markers have been studied to determine their potential in predicting disease outcome orresponse to the therapy. Purpose: To investigate correlation p53, Bcl-2, c-Myc, and MMP-9 expressionto clinicopathologic parameter in head and neck squamous cell carcinoma patient in dr. Zainoel Abidinhospital. Methods: Cross sectional design study. The sample was consisted of 60 paraffin blocks ofhead and neck squamous cell carcinoma. Procedure of immunohistochemical staining used monoclonalantibodies against p53, Bcl-2, c-Myc, and MMP-9. Expression of p53 protein, Bcl-2, c-Myc, and MMP-9were analyzed by immunohistochemistry in head and neck squamous cell carcinoma. Then, the results were linked to clinicopathologic parameters such as age, sex, tumor location, tumor differentiation,lymph node metastasis and tumor stage, and statistically analyzed with Chi square. Results: The resultsshowed there were significant correlation between p53 expression level with local metastasis (p=0,021)and significant correlation of MMP-9 expression levels with tumor location (p=0,026). There were norelationship of p53, Bcl-2, cMyc and MMP-9 expressions based on age, sex, stage tumor, histologicdifferentiation, level of T, N, and distant metastases. Conclusion: There were relationships between p53expression with local metastasis and MMP-9 expression with tumor location in head and neck squamouscell carcinoma. Keywords: Head and neck squamous cell carcinoma, p53, Bcl-2, c-Myc, MMP-9


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