scholarly journals Identification of Novel Prognostic Markers Associated With Laryngeal Squamous Cell Carcinoma Using Comprehensive Analysis

2022 ◽  
Vol 11 ◽  
Author(s):  
Chao Huang ◽  
Jun He ◽  
Yi Dong ◽  
Li Huang ◽  
Yichao Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Differentially Expressed Gene ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Value Analysis ◽  
Gene Set

BackgroundLaryngeal squamous cell carcinoma (LSCC) is a leading malignant cancer of the head and neck. Patients with LSCC, in which the cancer has infiltrated and metastasized, have a poor prognosis. Therefore, there is an urgent need to identify more potential targets for drugs and biomarkers for early diagnosis.MethodsRNA sequence data from LSCC and patients’ clinical traits were obtained from the Gene Expression Omnibus (GEO) (GSE142083) and The Cancer Genome Atlas (TCGA) database. Differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify hub genes. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, prognostic value analysis, receiver operating characteristic (ROC) curve analysis, gene mutation analysis, tumor-infiltrating immune cell abundance profile estimation, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) were performed. Single-gene RNA sequencing data were obtained from the GSE150321 dataset. Cell proliferation and viability were confirmed by the CCK-8 assay and real-time PCR.ResultsA total of 701 DEGs, including 329 upregulated and 372 downregulated genes, were screened in the GSE142083 dataset. Using WGCNA, three modules were identified to be closely related to LSCC. After intersecting the DEGs and performing univariate and multivariate Cox analyses, a novel prognostic model based on three genes (SLC35C1, HOXB7, and TEDC2) for LSCC was established. Interfering TEDC2 expression inhibited tumor cell proliferation and migration.ConclusionsOur results show that SLC35C1, HOXB7, and TEDC2 have the potential to become new therapeutic targets and prognostic biomarkers for LSCC.

scholarly journals Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

2022 ◽  
Vol 9 ◽  
Author(s):  
Yixiu Yu ◽  
Jiamei Niu ◽  
Xingwei Zhang ◽  
Xue Wang ◽  
Hongquan Song ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Bioinformatics Analyses ◽  
Gene Set

ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.

Tra2β silencing suppresses cell proliferation in laryngeal squamous cell carcinoma via inhibiting PI3K/AKT signaling

2018 ◽  
Vol 129 (9) ◽  
Author(s):  
Hao‐Sheng Ni ◽  
Song‐Qun Hu ◽  
Xi Chen ◽  
Yi‐Fei Liu ◽  
Ting‐Ting Ni ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Akt Signaling

scholarly journals Targeting SKA3 suppresses the proliferation and chemoresistance of laryngeal squamous cell carcinoma via impairing PLK1–AKT axis-mediated glycolysis

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Wei Gao ◽  
Yuliang Zhang ◽  
Hongjie Luo ◽  
Min Niu ◽  
Xiwang Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Critical Role ◽  
In Vivo Experiments ◽  
Potential Strategy

Abstract Spindle and kinetochore-associated complex subunit 3 (SKA3) is a well-known regulator of chromosome separation and cell division, which plays an important role in cell proliferation. However, the mechanism of SKA3 regulating tumor proliferation via reprogramming metabolism is unknown. Here, SKA3 is identified as an oncogene in laryngeal squamous cell carcinoma (LSCC), and high levels of SKA3 are closely associated with malignant progression and poor prognosis. In vitro and in vivo experiments demonstrate that SKA3 promotes LSCC cell proliferation and chemoresistance through a novel role of reprogramming glycolytic metabolism. Further studies reveal the downstream mechanisms of SKA3, which can bind and stabilize polo-like kinase 1 (PLK1) protein via suppressing ubiquitin-mediated degradation. The accumulation of PLK1 activates AKT and thus upregulates glycolytic enzymes HK2, PFKFB3, and PDK1, resulting in enhancement of glycolysis. Furthermore, our data reveal that phosphorylation at Thr360 of SKA3 is critical for its binding to PLK1 and the increase in glycolysis. Collectively, the novel oncogenic signal axis “SKA3-PLK1-AKT” plays a critical role in the glycolysis of LSCC. SKA3 may serve as a prognostic biomarker and therapeutic target, providing a potential strategy for proliferation inhibition and chemosensitization in tumors, especially for LSCC patients with PLK1 inhibitor resistance.

scholarly journals Bioinformatic Analysis Reveals an Immune/Inflammatory-Related Risk Signature for Oral Cavity Squamous Cell Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Shuang Bai ◽  
Ying-Bin Yan ◽  
Wei Chen ◽  
Ping Zhang ◽  
Tong-Mei Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Training Dataset ◽  
High Morbidity ◽  
Biological Processes

High-throughput gene expression profiling has recently emerged as a promising technique that provides insight into cancer subtype classification and improved prediction of prognoses. Immune/inflammatory-related mRNAs may potentially enrich genes to allow researchers to better illustrate cancer microenvironments. Oral cavity squamous cell carcinoma (OC-SCC) exhibits high morbidity and poor prognosis compared to that of other types of head and neck squamous cell carcinoma (HNSCC), and these differences may be partially due to differences within the tumor microenvironments. Based on this, we designed an immune-related signature to improve the prognostic prediction of OC-SCC. A cohort of 314 OC-SCC samples possessing whole genome expression data that were sourced from The Cancer Genome Atlas (TCGA) database was included for discovery. The GSE41613 database was used for validation. A risk score was established using immune/inflammatory signatures acquired from the training dataset. Principal components analysis, GO analysis, and gene set enrichment analysis were used to explore the bioinformatic implications. When grouped by the dichotomized risk score based on the signature, this classifier could successfully discriminate patients with distinct prognoses within the training and validation cohorts (P<0.05 in both cohorts) and within different clinicopathological subgroups. Similar somatic mutation patterns were observed between high and low risk score groups, and different copy number variation patterns were also identified. Further bioinformatic analyses suggested that the lower risk score group was significantly correlated with immune/inflammatory-related biological processes, while the higher risk score group was highly associated with cell cycle-related processes. The analysis indicated that the risk score was a robust predictor of patient survival, and its functional annotation was well established. Therefore, this bioinformatic-based immune-related signature suggested that the microenvironment of OC-SCC could distinguish among patients with different underlying biological processes and clinical outcomes, and the use of this signature may shed light on future OC-SCC classification and therapeutic design.

scholarly journals Identification of Cell cycle Gene Signatures Predicting Survival in Patients with Lung Squamous Cell Carcinoma

2019 ◽  
Author(s):  
Lei Zhang ◽  
Zhe Zhang ◽  
Zhenglun Yu
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Test Series ◽  
Gene Signatures ◽  
Gene Set

Abstract Background:Lung cancer (LC) is one of the most important and common malignant tumors, and its incidence and mortality are increasing annually. Lung squamous cell carcinoma (LUSC) is the common pathological type of lung cancer. A small part of biomarkers have been confirmed to be related to the prognosis and survival by data excavation. However, the moderate forecast effect of a single gene biomarker is not accurate. Thus, we aimed to identify new gene signatures to better predict Lung squamous cell carcinoma ( LU SC). Methods : Using the mRNA-mining approach, we performed mRNA expression profiling in large lung squamous cell carcinoma cohorts (n= from The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis(GSVA) were accomplished, and connections between genes and cell cycle were found in the Cox proportional regression model. Results : We have confirmed a set of four genes (CDKN1A, CHEK2, E2F4 and RAD21) that were importantly associated with overall survival (OS) in the test series. Based on the research of the four-gene signature, the patients in the test series could be divided into high-risk and low-risk teams. Additionally, multivariate Cox regression analysis revealed that the prognostic power of the four-gene signature is independent of the clinical factors. Conclusion : Our study demonstrated the connections between the four-gene signature and cell cycle. Novel insights into the research mechanisms of cell cycle was also revealed regarding the biomarkers of a poor prognosis for lung squamous cell carcinoma patients.

scholarly journals Circulating exosome-derived miR-191-5p is a novel therapeutic biomarker for radiotherapy in esophageal squamous cell carcinoma patients

2020 ◽  
Author(s):  
HUAN WANG ◽  
Masayuki Kano ◽  
Yasunori Matsumoto ◽  
Takeshi Toyozumi ◽  
Satoshi Endo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Progression Free Survival ◽  
Gene Set Enrichment Analysis ◽  
Free Survival ◽  
Patient Prognosis ◽  
Low Expression

Abstract Background: Exosomes are nano-sized extracellular vesicles and are detectable in most body fluids. Circulating exosomal microRNAs are an easily obtained, and they could be minimally invasive biomarker for cancer treatment. Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive carcinomas. Radiotherapy is one of the most important treatment option for ESCC, and it would thus be extremely crucial to predict therapeutic sensitivity and the patient prognosis in advance. Methods: A search for miRNAs with a therapeutic biomarker in ESCC was performed using the miRNA expression signatures obtained from ESCC plasma before radiotherapy. miR-191-5p was selected because it was found to be associated with the prognosis in ESCC based on the findings of previous reports. As a result, we decided to perform more studies to elucidate the significance of miR-191-5p. Gain-of-function analyses were performed to evaluate the functional significance of miR-191-5p in ESCC progression. The effects of miR-191-5p on ESCC radiosensitivity were determined by cell proliferation, a clonogenic survival assay and an apoptosis assay. A gene set enrichment analysis was used to investigate the downstream signaling pathway related to the miR-191-5p functions. The 5-year progression-free survival (PFS) rate was used to directly compare the usefulness of these biomarkers for determining the patient prognosis between the miR-191-5p high expression patients and low expression patients. Results: A subset of seven microRNAs (miR-628, miR-363, miR-191-5p, miR-185, miR-148a, miR-320d, miR-30e) was identified to be candidates of therapeutic biomarker for ESCC patients underwent radiotherapy in a global microRNA expression analysis. A high miR-191-5p expression promoted ESCC cell proliferation, invasion and migration and induced G0/G1 to S/G2M transition. miRNA-191-5p overexpression promoted cell survival and reduced cell apoptosis after irradiation. Mechanistically, miR-191-5p may directly target death-associated protein kinase 1 (DAPK1) to induce radiation resistance via the MAPK-JNK pathway. The 5-year progression-free survival rate for ESCC patients who underwent radiotherapy with high circulating exosomal miR-191-5p expression was significantly lower than in those with a low expression. Conclusion: Tumor-derived exosomal miR-191-5p is a potential non-invasive biomarker for predicting the prognosis in esophageal cancer patients after radiotherapy.

scholarly journals A Novel Signature Derived from Metabolism-Related Genes GPT and SMS to Predict Prognosis of Laryngeal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Yujie Shen ◽  
Qiang Huang ◽  
Yifan Zhang ◽  
Chi-Yao Hsueh ◽  
Liang Zhou
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Cox Regression ◽  
External Validation ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Clinical Samples ◽  
Prognostic Signature

Abstract Background A growing body of evidence has suggested the involvement of metabolism in the occurrence and development of tumors. But the link between metabolism and laryngeal squamous cell carcinoma (LSCC) has rarely been reported. This study seeks to understand and explain the role of metabolic biomarkers in predicting the prognosis of LSCC. Methods We identified the differentially expressed metabolism-related genes (MRGs) through RNA-seq data of TCGA (The Cancer Genome Atlas) and GSEA (Gene set enrichment analysis). After the screening of protein-protein interaction (PPI), hub MRGs were analyzed by least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic signature. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) was applied to verify the effectiveness of the prognostic signature in four cohorts (TCGA cohort, GSE27020 cohort, TCGA-sub1 cohort and TCGA-sub2 cohort). The expressions of the hub MRGs in cell lines and clinical samples were verified by quantitative reverse transcriptase PCR (qRT-PCR). The immunofluorescence staining of the tissue microarray (TMA) was carried out to further verify the reliability and validity of the prognostic signature. Cox regression analysis was then used to screen for independent prognostic factors of LSCC and a nomogram was constructed based on the results. Results Among the 180 differentially expressed MRGs, 14 prognostic MRGs were identified. A prognostic signature based on two MRGs (GPT and SMS) was then constructed and verified via internal and external validation cohorts. Compared to the adjacent normal tissues, SMS expression was higher while GPT expression was lower in LSCC tissues, indicating poorer outcomes. The risk score proved the prognostic signature as an independent risk factor for LSCC in both internal and external validation cohorts. A nomogram based on these results was developed for clinical application. Conclusions Differentially expressed MRGs were found and proven to be related to the prognosis of LSCC. We constructed a novel prognostic signature based on MRGs in LSCC for the first time and verified via different cohorts from both databases and clinical samples. A nomogram based on this prognostic signature was developed.

scholarly journals FOXL2 expression might be a novel prognostic biomarker in patients with laryngeal squamous cell carcinoma

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091925
Author(s):  
Jun Ge ◽  
Li Jiang ◽  
Yuke Tian ◽  
Min Zheng ◽  
Meiling Huang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Prognostic Biomarker ◽  
Dna Amplification ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Gene Body

Objectives This study aimed to explore the expression profile of the Forkhead box protein L2 gene ( FOXL2) and to determine its prognostic value and associated epigenetic and genetic alterations in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methods Data for a subset of patients with LSCC (N = 116) were extracted from the head and neck squamous cell carcinoma dataset of The Cancer Genome Atlas and analyzed in relation to FOXL2 expression and survival. Results Aberrant FOXL2 expression was an independent prognostic factor for progression-free survival (PFS) (hazard ratio (HR): 2.63, 95% confidence interval (CI): 1.34–5.18) and overall survival (OS) (HR: 2.39, 95%CI: 1.28–4.46). Two gene-body CpG sites (cg10554436 and cg23637494) were moderately and positively correlated with FOXL2 expression. DNA amplification (+2/+1) was common (82/115, 71%) in LSCC, and FOXL2 expression was significantly upregulated in the high-amplification group (+2) compared with copy-neutral (0) cases. Conclusion Aberrant FOXL2 expression may be a novel prognostic biomarker for PFS and OS among patients with LSCC. FOXL2 upregulation may be related to gene-body hypermethylation and DNA amplification.

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