Dataset Information

Comprehensive analysis of the expression and prognosis for CDCAs in head and neck squamous cell carcinoma.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC), a tumor included oral cavity, lips, larynx, oropharynx, and the nasopharynx et al. The cell division cycle-associated (CDCA) protein family (CDCA1-8) critical for normal cell function and cancer cell proliferation. We explored the mutation signatures and expression levels of various CDCAs in detail in HNSCC. A comprehensive bioinformatics analysis pipeline based on copy number and gene expressions data from patients with HNSCC in order to given new insights into the possible functions and distinct prognostics that underlie CDCAs regulation. We compared the transcriptional expression of CDCAs in HNSCC and found significantly elevated mRNA expression of CDCA1-8 in HNSCC tissues across multiple datasets. We also found CDCA5/6/8 are over-expressed both transcriptionally and translationally in patients with HNSCC. Our results suggested that that mRNA levels of CDCA1/2/4/7 related to the prognosis and can be used as a new useful biomarker for predicting the survival of HNSCC patients. The top 5 CDCAs neighboring gene alterations in HNSCCs were found in MYC, STAG1, RAD21, KLHL9 and NDC80. Multivariable Cox proportional hazard model also showed that CD8+ T cells were higher (P<0.05) in HNSCC-HPV-pos patients and that this was related to CDCA1/2/3/4/5/7. This study utilizes online tools to conduct specific gene analyses from free open databases, but our study requires more large-scale genomics research and basic research.

SUBMITTER: Wu ZH

PROVIDER: S-EPMC7384661 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comprehensive analysis of the expression and prognosis for CDCAs in head and neck squamous cell carcinoma.

Wu Zeng-Hong ZH Fang Ming M Zhou Yan Y

PloS one 20200727 7

Head and neck squamous cell carcinoma (HNSCC), a tumor included oral cavity, lips, larynx, oropharynx, and the nasopharynx et al. The cell division cycle-associated (CDCA) protein family (CDCA1-8) critical for normal cell function and cancer cell proliferation. We explored the mutation signatures and expression levels of various CDCAs in detail in HNSCC. A comprehensive bioinformatics analysis pipeline based on copy number and gene expressions data from patients with HNSCC in order to given new ...[more]

PMID: 32716971

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Project description:AbstractMicroRNAs (miRNAs) play critical roles in carcinogenesis and development of cancers. In this study, we analyzed the eccentrically expressed miRNAs in head and neck squamous cell carcinoma (HNSCC) tissues based on the miRNA-Seq data of HNSCC patients available in the Cancer Genome Atlas database. Aberrant expression of 2589 miRNAs was detected in HNSCC tissues (1128 downregulated and 1461 upregulated). The differential expression levels of the miRNAs were further validated by analysis of 25 HNSCC samples and paired control tissues and compared with the Gene Expression Omnibus database to determine the candidate miRNAs. Quantitative reverse transcription polymerase chain reaction was used to compare the expression of these candidate miRNAs between 22 fresh HNSCC tissue samples and 11 control samples. In addition, the relationship between the expression of these candidate miRNAs and Tumor, Node, Metastases staging of HNSCC was analyzed. Compared with the expression in control tissues, the levels of hsa-miR-410-3p, hsa-miR-411-5p, hsa-miR-125b-2-3p, and hsa-miR-99a-3p were significantly lower in HNSCC. According to the Cancer Genome Atlas dataset analyzed, all 4 miRNAs were shown to inhibit tumor progression (T stage), positive lymph node metastasis (N stage), and distant metastasis (M stage) in HNSCC. Kyoto Encyclopedia of Genes and Genomes analysis showed that genes regulated by these 4 miRNAs were enriched in certain pathways, including the transforming growth factor-? signaling pathway and the Hippo pathway. Enriched gene ontology terms mainly included regulation of transcription, cell proliferation, and apoptosis, which are well-characterized functions of miRNAs. Moreover, all 4 miRNAs inhibited the progression of primary tumors (T stage) and metastasis of regional lymph nodes (N stage). The top 4 aberrantly expressed miRNAs identified in this study have great clinical value in developing strategies for early diagnosis and treatment of HNSCC. More intensive studies are required to elucidate the mechanism underlying the roles of these miRNAs in HNSCC.

Project description:Head and neck squamous carcinoma (HNSCC) is highly infiltrated by immune cells, including tumor-infiltrating lymphocytes and myeloid lineage cells. In the tumor microenvironment, tumor cells orchestrate a highly immunosuppressive microenvironment by secreting immunosuppressive mediators, expressing immune checkpoint ligands, and downregulating human leukocyte antigen expression. In the present study, we aimed to comprehensively profile the immune microenvironment of HNSCC using gene expression data obtained from public database. We calculated enrichment scores of 33 immune cell types based on gene expression data of HNSCC tissues and adjacent non-cancer tissues. Based on these scores, we performed non-supervised clustering and identified three immune signatures-cold, lymphocyte, and myeloid/dendritic cell (DC)-based on the clustering results. We then compared the clinical and biological features of the three signatures. Among HNSCC and non-cancer tissues, human papillomavirus (HPV)-positive HNSCCs exhibited the highest scores in various immune cell types, including CD4+ T cells, CD8+ T cells, B cells, plasma cells, basophils, and their subpopulations. Among the three immune signatures, the proportions of HPV-positive tumors, oropharyngeal cancers, early T tumors, and N factor positive cases were significantly higher in the lymphocyte signature than in other signatures. Among the three signatures, the lymphocyte signature showed the longest overall survival (OS), especially in HPV-positive patients, whereas the myeloid/DC signature demonstrated the shortest OS in these patients. Gene set enrichment analysis revealed the upregulation of several pathways related to inflammatory and proinflammatory responses in the lymphocyte signature. The expression of PRF1, IFNG, GZMB, CXCL9, CXCL10, PDCD1, LAG3, CTLA4, HAVCR2, and TIGIT was the highest in the lymphocyte signature. Meanwhile, the expression of PD-1 ligand genes CD274 and PDCD1LG2 was highest in the myeloid/DC signature. Herein, our findings revealed the transcriptomic landscape of the immune microenvironment that closely reflects the clinical and biological significance of HNSCC, indicating that molecular profiling of the immune microenvironment can be employed to develop novel biomarkers and precision immunotherapies for HNSCC.

Dataset Information

Comprehensive analysis of the expression and prognosis for CDCAs in head and neck squamous cell carcinoma.

Publications

Comprehensive analysis of the expression and prognosis for CDCAs in head and neck squamous cell carcinoma.

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