Identification of Potential Genes both Differentially Expressed and Regulated by Differential Methylation Regions in Oral Squamous Cell Carcinoma

Cell Carcinoma ◽

Squamous Cell ◽

Patient Survival ◽

Biological Process ◽

Differential Methylation ◽

Hub Genes ◽

Hnscc Patient

Abstract Background: The aberrant methylation included hypermethylation and hypomethylation plays significant role in the progression of many kind of cancers but poorly investigated in oral squamous cell carcinoma (OSCC). Methods: GSE123781 and GSE87053 were used to identify the differential methylation regions (DMRs) by R software. the targeted genes regulated by DMRs were predicted by wANNOVAR. The biological process, cellular component, molecular function and cell pathways of common targeted genes between GSE123781 and GSE87053 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis. The hub genes in common targeted genes both associated with cancer biological process and cancer cell pathways were identified by protein to protein interaction network (PPI). Finally, the expression level of hub genes and correspondence relationship with head and neck squamous cell carcinoma (HNSCC) patient survival were confirmed by The Cancer Genome Atlas (TCGA) dataset. Results: There are 372 common targeted genes regulated by DMRs between GSE123781 and GSE87053 and RUNX family transcript factor 1 (RUNX1), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), laminin subunit beta 1 (LAMB1), integrin subunit alpha M (ITGAM), interleukin 2 receptor subunit alpha (IL2RA), interleukin 10 (IL10), FYN proto-oncogene, Src family tyrosine kinase (FYN), cholinergic receptor muscarinic 1 (CHRM1) and C-C motif chemokine receptor 1 (CCR1) are hub genes in common targeted genes. Furthermore, RUNX1, PIK3R1, PIK3CD, LAMB1, ITGAM, IL2RA, IL10, FYN, CHRM1 and CCR1 differentially expressed in HNSCC tissues and the overexpressed genes PIK3CD, LAMB1 and IL10 could lead to the decrease of HNSCC patient survival. Conclusions: PIK3CD, LAMB1 and IL10 both differentially expressed and regulated by DMRs are quite associated with the progression of OSCC and the survival of HNSCC patients, which has much potential to be new biomarkers in targeted therapy of OSCC.

Identification of Differential Methylation Regions and Correspondence Targeted Genes in Oral Squamous Cell Carcinoma

10.21203/rs.3.rs-27701/v1 ◽

2020 ◽

Author(s):

Yan Niu ◽

Qiusheng Shan ◽

Yuanling Guo

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Biological Process ◽

Enrichment Analysis ◽

Differential Methylation ◽

Hub Genes ◽

R Software

Abstract Background The differential methylation included hypermethylation and hypomethylation plays significant role in the progression of many kind of cancers but study little in oral squamous cell carcinoma (OSCC). Methods GSE123781 and GSE87053 was used to analysis the differential methylation regions (DMRs) and predict the target genes in OSCC by R software and wANNOVAR respectively. the biological process and cell pathways of common targeted genes between GSE123781 and GSE87053 were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis. The hub genes (hub genes 1) in common targeted genes associated with cancer biological process was identified by protein to protein interaction network (PPI). In addition, GSE74530 and GSE30784 was used to identify common differentially expressed genes (DEGs) in OSCC by R software. The biological process and cell pathways of common DEGs was analyzed by GO and KEGG enrichment analysis. The hub genes (hub genes 2) in common DEGs associated with cancer biological process was identified by PPI network. The significant hub genes between hub genes 1 and hub genes 2 were identified by Venn picture. Finally, the expression level of significant hub genes and correspondence relationship with head and neck squamous cell carcinoma (HNSCC) patient survival were confirmed by The Cancer Genome Atlas (TCGA) dataset. Results There are 2146 common targeted genes regulated by DMRs between GSE123781 and GSE87053 and 278 hub genes in common targeted genes associated with cancer biological process. In addition, there are 895 common DEGs between GSE74530 and GSE30784 and 144 hub genes in common DEGs associated with cancer biological process. There are 9 significant hub genes between hub genes 1 and hub genes 2. Finally, these 9 significant hub genes differentially expressed in HNSCC tissues except CCR7 and quite associated with the survival of HNSCC patients. Conclusions CCR7, ETS1, RUNX3, CCR1, C3AR1, LAMB1, IRF7, LGALS3 and CDKN3 both are DEGs and regulated by DMRs in OSCC, which are quite associated with the progression of OSCC and the survival of HNSCC patients. All of these genes have much potential to be new biomarkers in targeted therapy of OSCC.

Integrative Multi−Omics Analysis Reveals Candidate Biomarkers for Oral Squamous Cell Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.794146 ◽

2022 ◽

Vol 11 ◽

Author(s):

Zhengqing Wan ◽

Haofeng Xiong ◽

Xian Tan ◽

Tong Su ◽

Kun Xia ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Differentially Expressed Genes ◽

Squamous Cell ◽

Therapeutic Targets ◽

Integrative Approach ◽

Hub Genes ◽

Ppi Networks

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Due to the lack of early detection and treatment, the survival rate of OSCC remains poor and the incidence of OSCC has not decreased during the past decades. To explore potential biomarkers and therapeutic targets for OSCC, we analyzed differentially expressed genes (DEGs) associated with OSCC using RNA sequencing technology. Methylation−regulated and differentially expressed genes (MeDEGs) of OSCC were further identified via an integrative approach by examining publicly available methylomic datasets together with our transcriptomic data. Protein−protein interaction (PPI) networks of MeDEGs were constructed and highly connected hub MeDEGs were identified from these PPI networks. Subsequently, expression and survival analyses of hub genes were performed using The Cancer Genome Atlas (TCGA) database and the Gene Expression Profiling Interactive Analysis (GEPIA) online tool. A total of 56 upregulated MeDEGs and 170 downregulated MeDEGs were identified in OSCC. Eleven hub genes with high degree of connectivity were picked out from the PPI networks constructed by those MeDEGs. Among them, the expression level of four hub genes (CTLA4, CDSN, ACTN2, and MYH11) were found to be significantly changed in the head and neck squamous carcinoma (HNSC) patients. Three hypomethylated hub genes (CTLA4, GPR29, and TNFSF11) and one hypermethylated hub gene (ISL1) were found to be significantly associated with overall survival (OS) of HNSC patients. Therefore, these hub genes may serve as potential DNA methylation biomarkers and therapeutic targets of OSCC.

The integration of differentially expressed genes based on multiple microarray datasets for prediction of the prognosis in oral squamous cell carcinoma

Bioengineered ◽

10.1080/21655979.2021.1947076 ◽

2021 ◽

Vol 12 (1) ◽

pp. 3309-3321

Author(s):

Yinuan Zhao ◽

Jiacheng Huang ◽

Jianzhi Chen

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Differentially Expressed Genes ◽

Squamous Cell ◽

Microarray Datasets

Identifying an lncRNA-Related ceRNA Network to Reveal Novel Targets for a Cutaneous Squamous Cell Carcinoma

Biology ◽

10.3390/biology10050432 ◽

2021 ◽

Vol 10 (5) ◽

pp. 432

Author(s):

Yaqin Xu ◽

Yingying Dong ◽

Yunhua Deng ◽

Qianrong Qi ◽

Mi Wu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Biological Process ◽

Normal Skin ◽

Expression Patterns ◽

Therapeutic Targets ◽

Cutaneous Squamous Cell Carcinoma ◽

Cerna Network

A cutaneous squamous cell carcinoma (cSCC) derived from keratinocytes is the second most common cause of non-melanoma skin cancer. The accumulation of the mutational burden of genes and cellular DNA damage caused by the risk factors (e.g., exposure to ultraviolet radiation) contribute to the aberrant proliferation of keratinocytes and the formation of a cSCC. A cSCC encompasses a spectrum of diseases that range from recursor actinic keratosis (AK) and squamous cell carcinoma (SCC) in situ (SCCIS) to invasive cSCCs and further metastatic SCCs. Emerging evidence has revealed that lncRNAs are involved in the biological process of a cSCC. According to the ceRNA regulatory theory, lncRNAs act as natural miRNA sponges and interact with miRNA response elements, thereby regulating the mRNA expression of their down-stream targets. This study was designed to search for the potential lncRNAs that may become potential therapeutic targets or biomarkers of a cSCC. Considering the spirit of the study to be adequately justified, we collected microarray-based datasets of 19 cSCC tissues and 12 normal skin samples from the GEO database (GSE42677 and GSE45164). After screening the differentially expressed genes via a limma package, we identified 24 differentially expressed lncRNAs (DElncRNAs) and 3221 differentially expressed mRNAs (DEmRNAs). The miRcode, miRTarBase, miRDB and TargetScan databases were used to predict miRNAs that could interact with DElncRNAs and DEmRNAs. A total of 137 miRNA-lncRNA and 221 miRNA-mRNA pairs were retained in the ceRNA network, consisting of 31 miRNAs, 11 DElncRNAs and 155 DEmRNAs. For the functional analysis, the top enriched biological process was enhancer sequence-specific DNA binding in Gene Ontology (GO) terms. The FoxO signaling pathway, autophagy and cellular senescence were the top enrichment terms based on a Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The combination of a STRING tool and Cytoscape software (plug-in MCODE) identified five core mRNAs and built a core mRNA-associated ceRNA network. The expression for five identified core mRNAs and their related nine lncRNAs was validated using the external dataset GSE7553. Finally, one lncRNA HLA-F-AS1 and three mRNAs named AGO4, E2F1 and CCND1 were validated with the same expression patterns. We speculate that lncRNA HLA-F-AS1 may sponge miR-17-5p or miR-20b-5p to regulate the expression of CCND1 and E2F1 in the cSCC. The present study may provide potential diagnostic and therapeutic targets for cSCC patients.

Transcriptome analysis reveals differentially expressed lncRNAs between oral squamous cell carcinoma and healthy oral mucosa

Oncotarget ◽

10.18632/oncotarget.16358 ◽

2017 ◽

Vol 8 (19) ◽

pp. 31521-31531 ◽

Cited By ~ 43

Author(s):

Lu Feng ◽

John R. Houck ◽

Pawadee Lohavanichbutr ◽

Chu Chen

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Oral Mucosa ◽

Squamous Cell ◽

Transcriptome Analysis ◽

Differentially Expressed

Salivary Circular RNAs Hsa_Circ_0001874 and Hsa_Circ_0001971 as Novel Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000491624 ◽

2018 ◽

Vol 47 (6) ◽

pp. 2511-2521 ◽

Cited By ~ 31

Author(s):

Si-Yu Zhao ◽

Jun Wang ◽

Shao-Bo Ouyang ◽

Zi-Kun Huang ◽

Lan Liao

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Roc Curve ◽

Tnm Stage ◽

Circular Rnas ◽

Healthy Controls ◽

Novel Biomarkers

Background/Aims: Recent studies have demonstrated that circular RNAs (circRNAs) can serve as potential molecular markers for disease diagnosis. However, little is known about their diagnostic potential for oral squamous cell carcinoma (OSCC). This study aimed to determine the expression of circRNAs in the saliva of OSCC patients to identify novel biomarkers for OSCC screening. Methods: Microarray screening of circRNA was performed to identify differentially expressed circRNAs in saliva from 3 OSCC patients compared with 3 healthy controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results, and the association between these confirmed salivary circRNAs and clinicopathological features was analyzed using the chi-squared test. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the circRNAs identified. Preoperative expression and postoperative expression (1 month after the surgery) of hsa_circ_0001874 and hsa_circ_0001971 was also determined. Results: Our results indicated 12 upregulated and 20 downregulated circRNAs in the saliva from the OSCC patients compared with that from the healthy controls. Among the differentially expressed circRNAs, hsa_circ_0001874, hsa_circ_0001971, and hsa_circ_0008068 were upregulated and hsa_circ_0000140, hsa_circ_0002632, and hsa_circ_0008792 were downregulated in the OSCC group versus the healthy group. Clinical data indicated that salivary hsa_circ_0001874 was correlated with TNM stage (P=0.006) and tumor grade (P=0.023) and that hsa_circ_0001971 was correlated with TNM stage (P=0.019). The combination of hsa_circ_0001874 and hsa_circ_0001971 showed an area under the ROC curve of 0.922 (95% confidence interval, 0.883-0.961; P< 0.001). The risk score based on the combination of hsa_circ_0001874 and hsa_circ_0001971 also discriminated patients with OSCC from patients with oral leukoplakia (P< 0.001). Moreover, the expression levels of salivary hsa_circ_0001874 and hsa_circ_0001971 were clearly decreased in the postoperative samples compared with preoperative samples (P< 0.001). Conclusions: This is the first study to demonstrate the potential of salivary hsa_circ_0001874 and hsa_circ_0001971 as biomarkers for the diagnosis of OSCC.

SCCA, TSGF, and the Long Non-Coding RNA AC007271.3 are Effective Biomarkers for Diagnosing Oral Squamous Cell Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000489741 ◽

2018 ◽

Vol 47 (1) ◽

pp. 26-38 ◽

Cited By ~ 15

Author(s):

Tingru Shao ◽

Jiaxin Huang ◽

Zenan Zheng ◽

Qingqing Wu ◽

Tiancai Liu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Case Control Study ◽

Case Control ◽

Normal Controls ◽

Control Study ◽

Potential Biomarkers

Background/Aims: Oral squamous cell carcinoma (OSCC) is one of the most lethal malignancies worldwide and the most common type of oral cancer, characterized by invasive growth, frequent regional metastases, high recurrence, and poor prognosis. In the current study, we investigated the use of long non-coding RNAs (lncRNAs), tumor-specific growth factor (TSGF), and squamous cell carcinoma antigen (SCCA) as potential biomarkers for OSCC screening. Methods: LncRNA expression was measured by microarray analysis in three sets of OSCC and paired normal mucosal tissues. The potential lncRNAs involved in OSCC development were investigated by bioinformatics and verification experiments. We also determined the expression of these potential biomarkers in tissue and serum samples in a case–control study of 80 OSCC cases and 70 controls. Receiver operating characteristics, decision curve analysis, and the combined detection of lncRNA AC007271.3, TSGF, and SCCA were carried out to screen for OSCC biomarkers. Results: A total of 691 lncRNAs (433 upregulated and 258 downregulated) were differentially expressed in OSCC tissues compared with normal controls (p< 0.05). Based on Gene Ontology and pathway analysis, we selected four differentially expressed lncRNAs (AC007271.3, AC007182.6, LOC283481, and RP11-893F2.9), and showed that aberrant AC007271.3 levels in OSCC patients were significantly associated with clinical stage, especially in early-stage disease, in an expanded case–control study. The combination of AC007271.3 and SCCA (AUC=0.902, p< 0.001) showed significantly better ability to discriminate between OSCC and controls compared with SCCA or AC007271.3 alone. Serum AC007271.3, SCCA, and TSGF levels could also discriminate between OSCC and normal controls with sensitivities of 77.6%, 55.0%, and 63.3%, and specificities of 84.5%, 93.3%, and 66.7%, respectively. Conclusions: These results suggest that AC007271.3, SCCA, and TSGF could be novel circulating biomarkers for the determination of OSCC. However, further validation in large-scale prospective studies is necessary.