scholarly journals Clinical Significance of the Interleukin 24 mRNA Level in Head and Neck Squamous Cell Carcinoma and Its Subgroups: An In Silico Investigation

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Lan-Lan Qiu ◽  
Xiao-Guohui Zhang ◽  
Gang Chen ◽  
Yi-Wu Dang ◽  
Zhi-Guang Huang ◽  
...  

IL24 mRNA is known to have an apoptotic effect on cancer cells but not on noncancer cells. However, the expression level of the IL24 mRNA in head and neck squamous cell carcinoma (HNSCC) and its subgroups is rarely studied. In this study, the clinical implication of IL24 mRNA was evaluated in the common subgroups of HNSCC, including oral squamous cell carcinoma (OSCC), nasopharyngeal carcinoma (NPC), and laryngeal squamous cell carcinoma (LSCC) for analysis. Substantial IL24 mRNA expression data were calculated from several databases, such as the Gene Expression Omnibus (GEO), ArrayExpress, Sequence Read Archive (SRA), ONCOMINE, and The Cancer Genome Atlas (TCGA) databases. We ultimately collected a total of 41 microarrays and RNA-seq including 1,564 HNSCC and 603 noncancer tissue samples. IL24 mRNA was highly expressed in OSCC, LSCC, and NPC as shown by the separated standard mean difference (SMD), as well as HNSCC as a whole part (SMD = 1.47, 95% confdence interval (CI) = 1.24−1.70, P<0.0001). In all subgroups, the IL24 mRNA upregulation had the ability to distinguish cancer from noncancer tissue with area under the curves (AUCs) of the summary receiver operating characteristic (sROC) higher than 0.85. In conclusion, IL24 mRNA may be used as a potential marker for cancer screening, and its clinical diagnostic value needs to be further studied. It also provides a new idea for the treatment of the IL24 gene in HNSCC and its subgroups in the future.

2020 ◽  
Author(s):  
Ziyan Zhou ◽  
Wu Wenling ◽  
Li Jixi ◽  
Liu Chang ◽  
Xiao Zixi ◽  
...  

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer subtype globally, associated with a high rate of morbidity and mortality. However, the target genes of miR-221-3p and the underlying mechanism involved in HNSCC were not known. Therefore, in the current study, we studied the role of miR-221-3p in the HNSCC. Methods Tissues collected from 48 control and 21 HNSCC patients were processed to check the differential expression of miR-221-3p by Real-time RT-Polymerase Chain Reaction (RT-qPCR). Overexpression of microRNA-221-3p (miR-221-3p) is significantly correlated to the onset and progression of HNSCC. We also conducted the meta-analysis of the cancer literature from the cancer genome atlas (TCGA) and the Gene Expression Omnibus (GEO) database to estimate the expression of miR-221-3p in HNSCC. The miR-221-3p target genes in the HNSCC were predicted with the miRWalk and TCGA databases, and functionally annotated via the Gene Ontology Finally, Spearman’s analysis was used to determine the role of the related target genes in important pathways involved in the development of HNSCC. Results We observed a significantly higher expression of miR-221-3p in HNSCC compared to the normal with a summary receiver operating characteristic (sROC) of 0.86(95% Cl: 0.83,0.89). The KEGG and GO comprehensive analysis predicted that miR-221-3p might be involved in the development of HNSCC through the following metabolic pathways, viz Drug metabolism - cytochrome P450 UGT1A7 and MAOB may be important genes for the role of mir-221-3p. Conclusions Our results indicate that miR-221-3p may be used as a non-invasive and hypersensitive biomarker in the diagnosis. Thus, it can be concluded that miR-221-3p is an extremely important gene locus involved in the process of the deterioration and eventual tumorigenesis of HNSCC.


2020 ◽  
Author(s):  
Ziyan Zhou ◽  
Wenling Wu ◽  
Jixi Li ◽  
Chang Liu ◽  
Zixi Xiao ◽  
...  

Abstract BackgroundHead and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer subtype globally, associated with a high rate of morbidity and mortality. However, the target genes of miR-221-3p and the underlying mechanism involved in HNSCC were not known. Therefore, in the current study, we studied the role of miR-221-3p in the HNSCC. MethodsTissues collected from 48 control and 21 HNSCC patients were processed to check the differential expression of miR-221-3p by RT-qPCR. Overexpression of microRNA-221-3p (miR-221-3p) is significantly correlated to the onset and progression of HNSCC. We also conducted the meta-analysis of the cancer literature from the cancer genome atlas (TCGA) and the Gene Expression Omnibus (GEO) database to estimate the expression of miR-221-3p in HNSCC. The miR-221-3p target genes in the HNSCC were predicted with the miRWalk and TCGA databases, and functionally annotated via the Gene Ontology Finally, Spearman’s analysis was used to determine the role of the related target genes in important pathways involved in the development of HNSCC. ResultsWe observed a significantly higher expression of miR-221-3p in HNSCC compared to the normal with a summary receiver operating characteristic (sROC) of 0.86(95% Cl: 0.83,0.89). The KEGG and GO comprehensive analysis predicted that miR-221-3p might be involved in the development of HNSCC through the following metabolic pathways, viz Drug metabolism - cytochrome P450 UGT1A7 and MAOB may be important genes for the role of mir-221-3p.ConclusionsOur results indicate that miR-221-3p may be used as a non-invasive and hypersensitive biomarker in the diagnosis. Thus, it can be concluded that miR-221-3p is an extremely important gene locus involved in the process of the deterioration and eventual tumorigenesis of HNSCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Jing ◽  
Dandan Liu ◽  
Qingchuan Lai ◽  
Linqi Li ◽  
Mengqian Zhou ◽  
...  

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.


2021 ◽  
Vol 2021 ◽  
pp. 1-24
Author(s):  
Yubing Chen ◽  
Mingjiang Liu ◽  
Hu Jin ◽  
Bo Peng ◽  
Luo Dai ◽  
...  

Background. MicroRNA-1-3p (miR-1-3p) exerts significant regulation in various tumor cells, but its molecular mechanisms in head and neck squamous cell carcinoma (HNSCC) are still ill defined. This study is aimed at detecting the expression of miR-1-3p in HNSCC and at determining its significant regulatory pathways. Methods. Data were obtained from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Oncomine, ArrayExpress, Sequence Read Archive (SRA) databases, and additional literature. Expression values of miR-1-3p in HNSCC were analyzed comprehensively. The R language software was employed to screen differentially expressed genes, and bioinformatics assessment was performed. One sequence dataset (HNSCC: n = 484 ; noncancer: n = 44 ) and 18 chip datasets (HNSCC: n = 656 ; noncancer: n = 199 ) were obtained. Results. The expression of miR-1-3p in HNSCC was visibly decreased in compare with noncancerous tissues. There were distinct differences in tumor state ( P = 0.0417 ), pathological stage ( P = 0.0058 ), and T stage ( P = 0.0044 ). Comprehensive analysis of sequence and chip data also indicated that miR-1-3p was lowly expressed in HNSCC. The diagnostic performance of miR-1-3p in HNSCC is reflected in the sensitivity and specificity of the collection, etc. Bioinformatics analysis showed the possible biological process, cellular component, molecular function, and KEGG pathways of miR-1-3p in HNSCC. And ITGB4 was a possible target of miR-1-3p.Conclusions. miR-1-3p’s low expression may facilitate tumorigenesis and evolution in HNSCC through signaling pathways. ITGB4 may be a key gene in targeting pathways but still needs verification through in vitro experiments.


2019 ◽  
Author(s):  
Qiuchi Ran ◽  
Shengrong Long ◽  
Yan Ye ◽  
Diwas Sunchuri ◽  
Hong Liang ◽  
...  

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors. Many previous reports have already shown that the extent of infiltrating immune and stromal cells in tumor tissues and the tumor microenvironment (TME) cells play a significant role in the overall prognosis. Methods The convenient access to The Cancer Genome Atlas (TCGA) database facilitates global gene expression profiling and database mining in a large‐scale for potential correlation between genes and overall survival of a variety of malignancies including HNSCC. The quantification of the immune and stromal components in tumor tissues could be facilitated by calculating mmune scores and stromal scores on the basis of Estimation of stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm could facilitate the quantification of the immune and stromal components in tumor tissues. The effects of genes involved in immune and stromal cells on prognosis were categorized. Prognosis associated genes of HNSCC patients were further identified. Result This study showed that GIMAP6, SELL, TIFAB, KCNA3, P2RY8 and CCR4 may mediate immune response, extracellular matrix, and immunoglobulin binding via neutrophil activation in HNSCC. Conclusion Depicting a comprehensive landscape of the TME characteristics of HNSCC may therefore help to interpret the responses of HNSCC to immunotherapies and provide new strategies for the treatment of cancers.


Author(s):  
Ling Aye ◽  
Xiaole Song ◽  
Jingyi Yang ◽  
Li Hu ◽  
Xicai Sun ◽  
...  

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide. Checkpoint blockade immunotherapy has made tremendous progress in the treatment of a variety of cancers in recent years. Costimulatory molecules constitute the foundation of cancer immunotherapies and are deemed to be promising targets for cancer treatment. This study attempted to evaluate the potential value of costimulatory molecule genes (CMGs) in HNSCC.Materials and MethodsBased on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, we identified the prognostic value of CMGs in HNSCC. Subsequently, CMGs-based signature (CMS) to predict overall survival of HNSCC patients was established and validated. The differences of downstream pathways, clinical outcomes, immune cell infiltration, and predictive immunotherapy responses between different CMS subgroups were investigated via bioinformatic algorithms. We also explored the biological functions of TNFRSF12A, one risk factor of CMS, by in vitro experiments.ResultsAmong CMGs, 22 genes were related to prognosis based on clinical survival time in HNSCC. Nine prognosis-related CMGs were selected to establish CMS. CMS was an independent risk factor and could indicate the survival of HNSCC patients, the component of tumor-infiltrating lymphocytes, and the immunotherapy response rate. Functional enrichment analysis confirmed that CMS might involve immune-relevant processes. Additionally, TNFRSF12A was related to poor prognosis and enhanced malignant phenotype of HNSCC.ConclusionCollectively, CMS could accurately indicate prognosis, evaluate the tumor immune microenvironment, and predict possible immunotherapy outcomes for HNSCC patients.


2020 ◽  
Vol 29 ◽  
pp. 096368972092930
Author(s):  
Zeng-hong Wu ◽  
Yun-Tang ◽  
Qing Cheng

Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of the upper aerodigestive tract affecting the oral cavity, lips, paranasal sinuses, larynx, and nasopharynx. Proteogenomics combines proteomics and genomics and employs mass spectrometry and high-throughput sequencing technologies to identify novel peptides. The aim of this study was to identify potential protein biomarkers for clinical treatment of HNSCC. To achieve this, we utilized two sets of data, one on proteins from The Cancer Proteome Atlas (TCPA) and the other on gene expression from The Cancer Genome Atlas (TCGA) database, to evaluate dysfunctional proteogenomics microenvironment. Univariate Cox regression analysis was performed to examine the relationship between protein signatures and prognosis. A total of 19 proteins were significantly associated with overall survival (OS) of patients, of which E2F transcription factor 1 (E2F1; HR = 4.557, 95% CI = 1.810 to 11.469) and enhancer of zeste homolog 2 (EZH2; HR = 0.430, 95% CI = 0.187 to 0.984) were the most differentially expressed between patients with longer and shorter OS, respectively. Furthermore, multivariate Cox regression analysis on six proteins (ERALPHA, HER3, BRAF, P27, RAPTOR, and E2F1) was performed to build the prognostic model. The receiver operating characteristic curves were used to determine whether the expression pattern of survival-related proteins could provide an early prediction of the occurrence of HNSCC. Herein, we found an AUC of 0.720. Based on an online database, we identified novel protein markers for the prognosis of HNSCC. The findings of the present study may provide new insights into the development of new and reliable tools for precise cancer intervention.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ruoyan Cao ◽  
Suyang Liu ◽  
Jiayu Zhang ◽  
Xianyue Ren ◽  
Xijuan Chen ◽  
...  

TP53INP2 plays an important role in regulating gene transcription and starvation-induced autophagy, however, its function in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, we assessed the expression and prognostic value of TP53INP2. In addition, RNAseq, miRNAseq, copy number variation, and mutation profiles from The Cancer Genome Atlas (TCGA) dataset were applied to evaluate the distinctive genomic patterns related to TP53INP2 expression. We found that TP53INP2 expression was lower in HNSCC compared with normal controls. Patients with higher TP53INP2 expression had longer survival time. Knockdown of TP53INP2 promoted cell viability. Functional analysis exhibited that TP53INP2 was linked to DNA replication, DNA repair, cell cycle, and multiple metabolic pathways. Moreover, TP53INP2 might affect the expression of multiple genes via enhancing the transcriptional activity of nuclear hormone receptors. A competing endogenous RNA (ceRNA) network consisting of 33 lncRNAs, eight miRNAs, and 13 mRNAs was constructed based on the expression of TP53INP2. Taken together, our study highlights the potential value of TP53INP2 in predicting the survival of HNSCC and its important role in the genesis and development of HNSCC.


Sign in / Sign up

Export Citation Format

Share Document