scholarly journals Identification of key candidate genes and pathways in oral squamous cell carcinoma by integrated Bioinformatics analysis

2019 ◽  
Author(s):  
Bo Zou ◽  
Jun Li ◽  
Kai Xu ◽  
Jian‑Lin Liu ◽  
Dao‑Ying Yuan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Candidate Genes ◽  
Squamous Cell ◽  
Bioinformatics Analysis

scholarly journals M1-like tumor-associated macrophages cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma via the IL6/Stat3/THBS1 feedback loop

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Yuanhe You ◽  
Zhuowei Tian ◽  
Zhong Du ◽  
Kailiu Wu ◽  
Guisong Xu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Rna Seq ◽  
Stat3 Pathway ◽  
Functional Roles

Abstract Background Tumor-associated macrophages (TAMs) have a leading position in the tumor microenvironment. Previously, we have demonstrated that M1-like TAMs activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma (OSCC). However, the functional roles and associated molecular mechanisms of the activated M1-like TAMs need to be further clarified in OSCC. Methods Conditioned Media (CM) were harvested from the exosome activated M1-like TAMs. We measured the malignant behaviors of OSCC under the treatment of CM from M1-like TAMs by performing colony forming assays, invasion assays, wound-healing assays, spheroid forming assays and in vivo xenograft experiments. The underlying mechanisms were investigated by RNA-seq, cytokines analysis, intracellular signaling pathway analysis, ChIP assays, bioinformatics analysis and validation. Results M1-like TAMs significantly promoted the epithelial-mesenchymal transition (EMT) process, and induced the cancer-stem like cells (CSCs) by upregulating the expression of MME and MMP14 in OSCC cells. Cytokine analysis revealed a shark increase of IL6 secretion from M1-like TAMs. Blocking IL6 in the CM from M1-like TAMs could significantly weaken its effects on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Cellular signaling assays indicated the activation of Jak/Stat3 pathway in the OSCC cells treated by the CM from M1-like TAMs. Blocking the activation of the Jak/Stat3 pathway could significantly weaken the effects of M1-like TAMs on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Further RNA-seq analysis and bioinformatics analysis revealed an increased expression of THBS1 in the OSCC cells treated by M1-like TAMs. Bioinformatics prediction and ChIP assays revealed the activation of Stat3 by CM from M1-like TAMs could directly promote the transcription of THBS1 in OSCC cells. Conclusions We proposed that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of OSCC via the IL6/Stat3/THBS1 feedback loop. A better understanding on the functional roles and associated molecular mechanisms of M1-like TAMs might facilitate the development of novel therapies for supplementing the current treatment strategies for OSCC patients.

scholarly journals Identification of a Gene Prognostic Signature for Oral Squamous Cell Carcinoma by RNA Sequencing and Bioinformatics

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yang-Yang Zhang ◽  
Ming-Hui Mao ◽  
Zheng-Xue Han
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Candidate Genes ◽  
Rna Sequencing ◽  
Squamous Cell ◽  
Risk Model ◽  
Ppi Network ◽  
Prognostic Signature

Objectives. Oral squamous cell carcinoma (OSCC) is the most common oral cancer and has a poor prognosis. We aimed to identify new biomarkers or potential therapeutic targets for OSCC. Materials and Methods. Four pairs of tumor and adjacent normal tissues were collected from OSCC patients, and differentially expressed genes (DEGs) were screened via high-throughput RNA sequencing (RNA-seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze the DEGs. A protein-protein interaction (PPI) network was established with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape, and two significant clusters were found. Candidate genes were screened by analyzing head and neck squamous cell carcinoma (HNSCC) data from The Cancer Genome Atlas (TCGA). A DEG-based risk model was established to predict the overall survival (OS) of OSCC patients via Kaplan-Meier analysis and the log-rank test. Furthermore, univariate Cox regression analysis was applied to assess associations between potential biomarkers and the overall survival rate. Results. Of 720 total DEGs, fifty-two DEGs in the two subclusters of the PPI network analysis were selected. A risk model was established, and five candidate genes (SPRR2E, ICOS, CTLA4, HTR1D, and CCR4) were identified as biomarkers of OS in OSCC patients. Conclusions. We successfully constructed a prognostic signature to predict prognosis and identified five candidate genes associated with the OS of OSCC patients that are potential tumor biomarkers and targets in OSCC.

scholarly journals Comparative sera proteomics analysis of differentially expressed proteins in oral squamous cell carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11548
Author(s):  
Yin-Ling Wong ◽  
Anand Ramanathan ◽  
Kar Mun Yuen ◽  
Wan Mahadzir Wan Mustafa ◽  
Mannil Thomas Abraham ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Acute Phase ◽  
Squamous Cell ◽  
Bioinformatics Analysis ◽  
Differentially Expressed ◽  
Complement C3 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Differentially Expressed Proteins

Background Oral squamous cell carcinoma (OSCC) has increased in incidence from 1990 to 2017, especially in South and Southeast Asia. It is often diagnosed at an advanced stage with a poor prognosis. Therefore, early detection of OSCC is essential to improve the prognosis of OSCC. This study aims to identify the differentially expressed serum proteins as potential biomarkers for oral squamous cell carcinoma (OSCC). Methods Comparative proteomics profiling of serum samples from OSCC patients, oral potentially malignant disorder (OPMD) patients, and healthy individuals were performed using two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS) (n = 60) and bioinformatics analysis. The enzyme-linked immunosorbent assay (ELISA) (n = 120) and immunohistochemistry (IHC) (n = 70) were used to confirm our findings. Results The 2-DE analysis revealed that 20 differentially expressed proteins were detected in OPMD and OSCC (p < 0.05). Bioinformatics analysis indicated that the activation of classical complement, liver X receptor/retinoid X receptor (LXR/RXR) activation, and acute phase response signaling pathway are associated with the development and progression of OSCC. Most of the detected proteins are acute-phase proteins and were related to inflammation and immune responses, including apolipoprotein A-I (APOA1), complement C3 (C3), clusterin (CLU), and haptoglobin (HP). The expression levels of CLU and HP in ELISA are consistent with the findings from the 2-DE analysis, except for the mean serum level of HP in OPMD, whereby it was slightly higher than that in control. IHC results demonstrated that CLU and HP are significantly decreased in OSCC tissues. Conclusion Decreased expression of CLU and HP could serve as complementary biomarkers of OSCC. These proteins may assist in predicting the outcomes of OSCC patients. However, a larger cohort is needed for further investigation.

scholarly journals Integrated Bioinformatics Analysis of mRNAs and miRNAs Identified Potential Biomarkers of Oral Squamous Cell Carcinoma

2020 ◽  
Vol 21 (6) ◽  
pp. 1841-1848 ◽  
Author(s):  
Nasrin Amiri-Dashatan ◽  
Mehdi Koushki ◽  
Ali Jalilian ◽  
Nayeb Ali Ahmadi ◽  
Mostafa Rezaei Tavirani
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Bioinformatics Analysis ◽  
Potential Biomarkers

scholarly journals An integrated approach for identification of a panel of candidate genes arbitrated for invasion and metastasis in oral squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samapika Routray ◽  
Ravindra Kumar ◽  
Keshava K. Datta ◽  
Vinuth N. Puttamallesh ◽  
Aditi Chatterjee ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Candidate Genes ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Integrated Approach ◽  
Diagnostic Tools ◽  
Invasion And Metastasis

AbstractOral squamous cell carcinoma (OSCC) is known for its aggressiveness associated with poor prognosis. The molecular mechanisms underlying the invasion and metastasis are still poorly understood. An improved understanding of these mechanisms shall precede the development of new diagnostic tools and targeted therapies. We report an integrated approach using bioinformatics to predict candidate genes, coupled with proteomics and immunohistochemistry for validating their presence and involvement in OSCC pathways heralding invasion and metastasis. Four genes POSTN, TNC, CAV1 and FSCN1 were identified. A protein–protein interaction network analysis teamed with pathway analysis led us to propose the role of the identified genes in invasion and metastasis in OSCC. Further analyses of archived FFPE blocks of various grades of oral cancer was carried out using TMT-based mass spectrometry and immunohistochemistry. Results of this study expressed a strong communiqué and interrelationship between these candidate genes. This study emphasizes the significance of a molecular biomarker panel as a diagnostic tool and its correlation with the invasion and metastatic pathway of OSCC. An insight into the probable association of CAF's and these biomarkers in the evolution and malignant transformation of OSCC further magnifies the molecular-biological spectrum of OSCC tumour microenvironment.

scholarly journals Bioinformatics analysis of dysregulated exosomal microRNAs derived from oral squamous cell carcinoma cells

2021 ◽  
Vol 63 (2) ◽  
pp. 174-178
Author(s):  
Tadashi Masaoka ◽  
Keiji Shinozuka ◽  
Kenshin Ohara ◽  
Hiromasa Tsuda ◽  
Kenichi Imai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Bioinformatics Analysis ◽  
Carcinoma Cells
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