Dataset Information

Identification of CCT3 as a prognostic factor and correlates with cell survival and invasion of head and neck squamous cell carcinoma.

ABSTRACT: Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The identification of effective markers for early diagnosis and prognosis is important for reducing mortality and ensuring that therapy for HNSCC is effective. Chaperonin-containing TCP-1 3 (CCT3) folds cancer-related proteins to control carcinogenesis. The prognostic value and growth association of CCT3 and HNSCC remain unknown. The GEO, Oncomine and UALCAN databases were used to examine CCT3 expression in HNSCC. A few clinical HNSCC samples with normal tissues were used to detect CCT3 expression by using immunohistochemistry method. The TCGA-HNSC dataset was used to evaluate the association between expression of CCT3 and prognosis. The molecular mechanism was investigated with gene set enrichment analysis (GSEA). CCK-8 and wound healing assays were used to detect cell growth and invasion of HNSCC, respectively. CCT3 expression was significantly up-regulated in HNSCC in both mRNA and protein levels. In addition, up-regulated CCT3 expression was associated with various clinicopathological parameters. High expression of CCT3 was significantly correlated with inferior survival of HNSCC patients. Knockdown of CCT3 significantly inhibited cell growth and invasion of HNSCC cell lines. GSEA analysis indicated that CCT3 was closely correlated with tumor-related signaling pathways and HNSCC cell survival. Our findings suggest that CCT3 is a biomarker of poor prognosis and related to the process of HNSCC.

SUBMITTER: Wang Y

PROVIDER: S-EPMC8529339 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Identification of CCT3 as a prognostic factor and correlates with cell survival and invasion of head and neck squamous cell carcinoma.

Wang Yan Y Liu Peicheng P Zhang Ziwei Z Wang Jiulong J Cheng Zhigang Z Fan Chengchao C

Bioscience reports 20211001 10

<h4>Background</h4>Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The identification of effective markers for early diagnosis and prognosis is important for reducing mortality and ensuring that therapy for HNSCC is effective. Chaperonin-containing TCP-1 3 (CCT3) folds cancer-related proteins to control carcinogenesis. The progn ...[more]

PMID: 34505628

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Project description:Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family and is involved in immune and inflammatory signaling. TYK2 is overexpressed in several types of cancers and promotes the invasion and proliferation of cancer cells. Nevertheless, the roles of TYK2 in the prognosis and immune infiltration of head and neck squamous cell carcinoma (HNSCC) remain to be elucidated. In this study, the expression of TYK2 in HNSCC was evaluated based on the data retrieved from multiple databases and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The prognostic potential of TYK2 in patients with HNSCC was analyzed by Kaplan-Meier curves and Cox regression analysis. A TYK2-related risk assessment model was subsequently constructed by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and stepwise multivariate Cox regression analysis. The association between the expression of TYK2 and the tumor immune microenvironment, immune checkpoints, and drug sensitivity was explored various packages in R. Cell function assays were finally used for exploring the effects of TYK2 on the growth and metastasis of HNSCC tumors. The expression of TYK2 was significantly upregulated in HNSCC and was found to be closely correlated with HPV status, gender, clinical grade, and TP53 mutation status. Survival analysis suggested that TYK2 is associated with better survival outcomes and acts as an independent prognostic indicator of HNSCC. The model constructed herein also performed well in terms of predicting patient prognosis. The expression of TYK2 was positively associated with the population of tumor-infiltrating immune cells, expression of immune checkpoint genes, and antitumor drug susceptibility. Functionally, TYK2 knockdown significantly promoted the proliferation, migration, and invasion of HNSCC cell lines in vitro. The findings demonstrated that TYK2 could serve as a suppressor of tumor growth and holds significant promise as a novel biomarker for assessing the prognosis of patients with HNSCC and aid in immunotherapy against HNSCC.

Project description:BackgroundTranscriptional dysregulation is one of the most important features of cancer genesis and progression. Applying gene expression dysregulation information to predict the development of cancers is useful for cancer diagnosis. However, previous studies mainly focused on the relationship between a single gene and cancer. Prognostic prediction using combined gene models remains limited.Materials and methodsGene expression profiles were downloaded from The Cancer Genome Atlas and the data sets were randomly divided into training data sets and test data sets. A six-gene signature associated with head and neck squamous cell carcinoma (HNSCC) and overall survival (OS) was identified according to a training cohort by using weighted gene correlation network analysis and least absolute shrinkage and selection operator Cox regression. The test data set and gene expression omnibus (GEO) data set were used to validate this signature.ResultsWe identified six candidate genes, namely, FOXL2NB, PCOLCE2, SPINK6, ULBP2, KCNJ18, and RFPL1, and, using a six-gene model, predicted the risk of death of head and neck squamous cell carcinoma in The Cancer Genome Atlas. At a selected cutoff, patients were clustered into low- and high-risk groups. The OS curves of the two groups of patients had significant differences, and the time-dependent receiver operating characteristics of OS, disease-specific survival (DSS), and progression-free survival (PFS) were as high as 0.766, 0.731, and 0.623, respectively. Then, the test data set and the GEO data set were used to evaluate our model, and we found that the OS time in the high-risk group was significantly shorter than in the low-risk group in both data sets, and the receiver operating characteristics of test data set were 0.669, 0.675, and 0.614, respectively. Furthermore, univariate and multivariate Cox regression analyses showed that the risk score was independent of clinicopathological features.ConclusionThe six-gene model could predict the OS of HNSCC patients and improve therapeutic decision-making.

Dataset Information

Identification of CCT3 as a prognostic factor and correlates with cell survival and invasion of head and neck squamous cell carcinoma.

Publications

Identification of CCT3 as a prognostic factor and correlates with cell survival and invasion of head and neck squamous cell carcinoma.

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