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

Background: 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 remains unknown. Methods: 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. Results: CCT3 expression was significantly upregulated in HNSCC in both mRNA and protein levels. In addition, upregulated 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. Conclusion: Our findings suggest that CCT3 is a biomarker of poor prognosis and related to the process of HNSCC.

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YRNAs: New Insights and Potential Novel Approach in Head and Neck Squamous Cell Carcinoma

Cells ◽

10.3390/cells9051281 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1281 ◽

Cited By ~ 3

Author(s):

Kacper Guglas ◽

Tomasz Kolenda ◽

Maciej Stasiak ◽

Magda Kopczyńska ◽

Anna Teresiak ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Gene Set Enrichment Analysis ◽

Neck Squamous Cell Carcinoma ◽

High Expression ◽

Ribonucleoprotein Particle ◽

Hnscc Cell

YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren’s syndrome. Deregulation of YRNAs has been confirmed in many cancer types, but not in head and neck squamous cell carcinoma (HNSCC). The main aim of this study was to determine the biological role of YRNAs in HNSCC, the expression of YRNAs, and their usefulness as potential HNSCC biomarkers. Using quantitative reverse transcriptase (qRT)-PCR, the expression of YRNAs was measured in HNSCC cell lines, 20 matched cancer tissues, and 70 FFPETs (Formaline-Fixed Paraffin-Embedded Tissue) from HNSCC patients. Using TCGA (The Cancer Genome Atlas) data, an analysis of the expression levels of selected genes, and clinical-pathological parameters was performed. The expression of low and high YRNA1 expressed groups were analysed using gene set enrichment analysis (GSEA). YRNA1 and YRNA5 are significantly downregulated in HNSCC cell lines. YRNA1 was found to be significantly downregulated in patients’ tumour sample. YRNAs were significantly upregulated in T4 stage. YRNA1 showed the highest sensitivity, allowing to distinguish healthy from cancer tissue. An analysis of TCGA data revealed that expression of YRNA1 was significantly altered in the human papilloma virus (HPV) infection status. Patients with medium or high expression of YRNA1 showed better survival outcomes. It was noted that genes correlated with YRNA1 were associated with various processes occurring during cancerogenesis. The GSEA analysis showed high expression enrichment in eight vital processes for cancer development. YRNA1 influence patients’ survival and could be used as an HNSCC biomarker. YRNA1 seems to be a good potential biomarker for HNSCC, however, more studies must be performed and these observations should be verified using an in vitro model.

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A panel of Transcription factors identified by data mining can predict the prognosis of head and neck squamous cell carcinoma

Cancer Cell International ◽

10.1186/s12935-019-1024-6 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Boxin Zhang ◽

Haihui Wang ◽

Ziyan Guo ◽

Xinhai Zhang

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Transcription Factors ◽

Cell Carcinoma ◽

Head And Neck ◽

Risk Score ◽

Squamous Cell ◽

Gene Set Enrichment Analysis ◽

Neck Squamous Cell Carcinoma ◽

Clinicopathological Parameters

Abstract Background Transcription factors (TFs) are responsible for the regulation of various activities related to cancer like cell proliferation, invasion, and migration. It is thought that, the measurement of TFs levels could assist in developing strategies for diagnosis and prognosis of cancer detection. However, due to lack of effective genome-wide tests, this cannot be carried out in clinical settings. Methods A complete assessment of RNA-seq data in samples of a head and neck squamous cell carcinoma (HNSCC) cohort in The Cancer Genome Atlas (TCGA) database was carried out. From the expression data of six TFs, a risk score model was developed and further validated in the GSE41613 and GSE65858 series. Potential functional roles were identified for the six TFs via gene set enrichment analysis. Results Based on our multi-TF signature, patients are stratified into high- and low-risk groups with significant variations in overall survival (OS) (median survival 2.416 vs. 5.934 years, log-rank test P < 0.001). The sensitivity and specificity evaluation of our multi-TF for 3-year OS in TCGA, GSE41613 and GSE65858 was 0.707, 0.679 and 0.605, respectively, demonstrating good reproducibility and robustness for predicting overall survival of HNSCC patients. Through multivariate Cox regression analyses (MCRA) and stratified analyses, we confirmed that the predictive capability of this risk score (RS) was not dependent on any of other factors like clinicopathological parameters. Conclusions With the help of a RS obtained from a panel of TFs expression signatures, effective OS prediction and stratification of HNSCC patients can be carried out.

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Identification of PSMD7as a prognostic factor correlated with immune infiltration in head and neck squamous-cell carcinoma

Bioscience Reports ◽

10.1042/bsr20203829 ◽

2021 ◽

Author(s):

Si Zhang ◽

Siwei Yu ◽

Jiulong Wang ◽

Zhigang Cheng

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Expression Profiles ◽

Locally Advanced ◽

Gene Set Enrichment Analysis ◽

Neck Squamous Cell Carcinoma ◽

Clinicopathological Parameters ◽

Immune Infiltration

Background: 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. Proteasome 26S subunit, non-ATPase 7 (PSMD7) is an ATP-independent component of the 19S regulatory subunit. The prognostic value of PSMD7and the association with immune infiltration in HNSCC remains unclear. Methods: The Sangerbox, Oncomine, UALCAN and HPA databases were used to examine PSMD7 expression profiles in HNSCC. The CVCDAP was used to analysis the association of PSMD7 with the prognosis of patients with HNSCC. The mechanism was investigated with gene set enrichment analysis (GSEA). The association between expression of PSMD7 and immune infiltration in HNSCC was investigated using the TIMER, TISIDB database and CIBERSORT algorithm. Results: PSMD7 expression was significantly upregulated in HNSCC compared to relative normal tissues. In addition, upregulated PSMD7 expression was associated with various clinicopathological parameters. High expression of PSMD7 suggested inferior survival of HNSCC patients. GSEA analysis and CERES score indicated that PSMD7 was closely correlated with tumor-related signaling pathways and cell survival. Functional analyses revealed that PSMD7 was positively correlated with various infiltration levels. Moreover, PSMD7 influenced the prognosis of HNSCC patients partially via immune infiltration. Conclusion: Our findings suggest that PSMD7 is associated poor prognosis in patients with HNSCC and plays an important role in tumor-related immune infiltration.

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Cav1/EREG/YAP Axis in the Treatment Resistance of Cav1-Expressing Head and Neck Squamous Cell Carcinoma

Cancers ◽

10.3390/cancers13123038 ◽

2021 ◽

Vol 13 (12) ◽

pp. 3038

Author(s):

Mickaël Burgy ◽

Aude Jehl ◽

Ombline Conrad ◽

Sophie Foppolo ◽

Véronique Bruban ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Lines ◽

Squamous Cell ◽

Cell Cycle Progression ◽

Locally Advanced ◽

Treatment Resistance ◽

Neck Squamous Cell Carcinoma ◽

Hnscc Cell

The EGFR-targeting antibody cetuximab (CTX) combined with radiotherapy is the only targeted therapy that has been proven effective for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Recurrence arises in 50% of patients with HNSCC in the years following treatment. In clinicopathological practice, it is difficult to assign patients to classes of risk because no reliable biomarkers are available to predict the outcome of HPV-unrelated HNSCC. In the present study, we investigated the role of Caveolin-1 (Cav1) in the sensitivity of HNSCC cell lines to CTX-radiotherapy that might predict HNSCC relapse. Ctrl- and Cav-1-overexpressing HNSCC cell lines were exposed to solvent, CTX, or irradiation, or exposed to CTX before irradiation. Growth, clonogenicity, cell cycle progression, apoptosis, metabolism and signaling pathways were analyzed. Cav1 expression was analyzed in 173 tumor samples and correlated to locoregional recurrence and overall survival. We showed that Cav1-overexpressing cells demonstrate better survival capacities and remain proliferative and motile when exposed to CTX-radiotherapy. Resistance is mediated by the Cav1/EREG/YAP axis. Patients whose tumors overexpressed Cav1 experienced regional recurrence a few years after adjuvant radiotherapy ± chemotherapy. Together, our observations suggest that a high expression of Cav1 might be predictive of locoregional relapse of LA-HNSCC.

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HOXB7 acts as an oncogenic biomarker in head and neck squamous cell carcinoma

Cancer Cell International ◽

10.1186/s12935-021-02093-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiang Wu ◽

Jin Li ◽

Tingyuan Yan ◽

Xueping Ke ◽

Xin Li ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Expression Pattern ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Clinicopathological Parameters ◽

Migration And Invasion ◽

Connectivity Map

Abstract Background The homeobox gene Homeobox B7 (HOXB7) is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, migration and invasion. However, its expression pattern and oncogenic role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we aimed to explore the expression pattern of HOXB7, its clinical significance as well as functional roles in HNSCC. Methods HOXB7 mRNA expression in HNSCC was determined by data mining and analyses from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The protein abundance of HOXB7 was measured by immunohistochemistry in 119 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The pro-tumorigenic roles of HOXB7 in HNSCC were further delineated in vitro by loss-of-function assay. And a xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for HOXB7. Results Bioinformatics analyses showed that HOXB7 mRNA was significantly overexpressed in 8 independent HNSCC datasets from TCGA and GEO databases. HOXB7 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with high pathological grade, advanced clinical stage, cervical node metastasis (P = 0.0195, 0.0152, 0.0300) and reduced overall and disease-free survival (P = 0.0014, 0.0007). Univariate and multivariate Cox regression analyses further revealed HOXB7 as an independent prognostic factor for patients’ overall survival. Moreover, HOXB7 knockdown significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in HNSCC cells, and resulted in compromised tumour growth in vivo. Furthermore, CMap (Connectivity map) analysis has identified three potential bioactive small molecule inhibitors (NU-1025, thiamine, vinburnine) for HOXB7 targeted therapy in HNSCC. Conclusions Our findings revealed that overexpression of HOXB7 was associates with tumour aggressiveness and unfavourable prognosis by serving a novel prognostic biomarker in HNSCC. Moreover, HOXB7 might be involved in the development and progression of HNSCC as an oncogene, and thereby might be a potential therapeutic target for HNSCC.

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Identification of potential core genes and pathways predicting pathogenesis in head and neck squamous cell carcinoma

Bioscience Reports ◽

10.1042/bsr20204148 ◽

2021 ◽

Author(s):

Mengmeng Wang ◽

Bin Zhong ◽

Man Li ◽

Yanjuan Wang ◽

Huaian Yang ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Small Molecules ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Potential Drug ◽

Hub Genes ◽

Potential Core ◽

Hnscc Cell

Head and neck squamous cell carcinoma (HNSCC) is the most common subtype of head and neck cancer; however, its pathogenesis and potential therapeutic targets remain largely unknown. In this study, we analyzed three gene expression profiles and screened differentially expressed genes (DEGs) between HNSCC and normal tissues. The DEGs were subjected to gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), protein–protein interaction (PPI), and survival analyses, while the connectivity map (CMap) database was used to predict candidate small molecules that may reverse the biological state of HNSCC. Finally, we measured the expression of the most relevant core gene in vitro and examined the effect of the top predicted potential drug against the proliferation of HNSCC cell lines. Among the 208 DEGs and ten hub genes identified, CDK1 and CDC45 were associated with unfavorable HNSCC prognosis, and three potential small molecule drugs for treating HNSCC were identified. Increased CDK1 expression was confirmed in HNSCC cells, and menadione, the top predicted potential drug, exerted significant inhibitory effects against HNSCC cell proliferation and markedly reversed CDK1 expression. Together, the findings of this study suggest that the ten hub genes and pathways identified may be closely related to HNSCC pathogenesis. In particular, CDK1 and CDC45 overexpression could be reliable biomarkers for predicting unfavorable prognosis in patients with HNSCC, while the new candidate small molecules identified by CMap analysis provide new avenues for the development of potential drugs to treat HNSCC.

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A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

Scientific Reports ◽

10.1038/srep36132 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 19

Author(s):

Aneesha Radhakrishnan ◽

Vishalakshi Nanjappa ◽

Remya Raja ◽

Gajanan Sathe ◽

Vinuth N. Puttamallesh ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Signaling Pathways ◽

Cell Lines ◽

Squamous Cell ◽

Therapeutic Target ◽

Neck Squamous Cell Carcinoma ◽

Dual Specificity ◽

Hnscc Cell

Abstract Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC.

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