scholarly journals Methylation-Based Classification of Cervical Squamous Cell Carcinoma into Two New Subclasses Differing in Immune-Related Gene Expression

2018 ◽  
Vol 19 (11) ◽  
pp. 3607 ◽  
Author(s):  
Xia Li ◽  
Yunpeng Cai
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immune Cell ◽  
Cervical Squamous Cell Carcinoma ◽  
Related Gene ◽  
Immune Related Gene

Cervical cancer is traditionally classified into two major histological subtypes, cervical squamous cell carcinoma (CSCC) and cervical adenocarcinoma (CA). However, heterogeneity exists among patients, comprising possible subpopulations with distinct molecular profiles. We applied consensus clustering to 307 methylation samples with cervical cancer from The Cancer Genome Atlas (TCGA). Fisher’s exact test was used to perform transcription factors (TFs) and genomic region enrichment. Gene expression profiles were downloaded from TCGA to assess expression differences. Immune cell fraction was calculated to quantify the immune cells infiltration. Putative neo-epitopes were predicted from somatic mutations. Three subclasses were identified: Class 1 correlating with the CA subtype and Classes 2 and 3 dividing the CSCC subtype into two subclasses. We found the hypomethylated probes in Class 3 exhibited strong enrichment in promoter region as compared with Class 2. Five TFs significantly enriched in the hypomethylated promoters and their highly expressed target genes in Class 3 functionally involved in the immune pathway. Gene function analysis revealed that immune-related genes were significantly increased in Class 3, and a higher level of immune cell infiltration was estimated. High expression of 24 immune genes exhibited a better overall survival and correlated with neo-epitope burden. Additionally, we found only two immune-related driver genes, CARD11 and JAK3, to be significantly increased in Class 3. Our analyses provide a classification of the largest CSCC subtype into two new subclasses, revealing they harbored differences in immune-related gene expression.

scholarly journals A Novel Immune-Related Prognostic Signature in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Zhang ◽  
Ping Chen ◽  
Qiang Zhou ◽  
Hongyan Wang ◽  
Qingquan Hua ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Related Gene ◽  
Gene Signatures ◽  
Immune Related Gene ◽  
Immune Related Genes

The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, very limited robust and reliable immunological biomarkers have been developed that are capable of estimating prognosis in HNSCC patients. In this study, we aimed to identify the effects of novel immune-related gene signatures (IRGs) that can predict HNSCC prognosis. Based on gene expression profiles and clinical data of HNSCC patient cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, a total of 439 highly variable expressed immune-related genes (including 239 upregulated and 200 downregulated genes) were identified by using differential gene expression analysis. Pathway enrichment analysis indicated that these immune-related differentially expressed genes were enriched in inflammatory functions. After process screening in the training TCGA cohort, six immune-related genes (PLAU, STC2, TNFRSF4, PDGFA, DKK1, and CHGB) were significantly associated with overall survival (OS) based on the LASSO Cox regression model. Integrating these genes with clinicopathological features, a multivariable model was built and suggested better performance in determining patients’ OS in the testing cohort, and the independent validation cohort. In conclusion, a well-established model encompassing both immune-related gene signatures and clinicopathological factors would serve as a promising tool for the prognostic prediction of HNSCC.

scholarly journals Bioinformatics analysis of DNMT1 expression and its role in head and neck squamous cell carcinoma prognosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jili Cui ◽  
Lian Zheng ◽  
Yuanyuan Zhang ◽  
Miaomiao Xue
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Hub Genes ◽  
Significant Difference ◽  
Dnmt1 Expression

AbstractHead and neck squamous cell carcinoma (HNSCC) is the sixth most common type of malignancy in the world. DNA cytosine-5-methyltransferase 1 (DNMT1) play key roles in carcinogenesis and regulation of the immune micro-environment, but the gene expression and the role of DNMT1 in HNSCC is unknown. In this study, we utilized online tools and databases for pan-cancer and HNSCC analysis of DNMT1 expression and its association with clinical cancer characteristics. We also identified genes that positively and negatively correlated with DNMT1 expression and identified eight hub genes based on protein–protein interaction (PPI) network analysis. Enrichment analyses were performed to explore the biological functions related with of DNMT1. The Tumor Immune Estimation Resource (TIMER) database was performed to explore the relationship between DNMT1 expression and immune-cell infiltration. We demonstrated that DNMT1 gene expression was upregulated in HNSCC and associated with poor prognosis. Based on analysis of the eight hub genes, we determined that DNMT1 may be involved in cell cycle, proliferation and metabolic related pathways. We also found that significant difference of B cells infiltration based on TP 53 mutation. These findings suggest that DNMT1 related epigenetic alterations have close relationship with HNSCC progression, and DNMT1 could be a novel diagnostic biomarker and a promising therapeutic target for HNSCC.

scholarly journals Expression of Angiopoietin and VEGF in cervical cancer and its clinical significance

2018 ◽  
Vol 13 (1) ◽  
pp. 527-532
Author(s):  
Qingyuan Lv ◽  
Weijuan Zhong ◽  
Xiabin Ye ◽  
Yang Lv ◽  
Haiying Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Significance ◽  
Squamous Cell ◽  
Tumor Tissue ◽  
Neoadjuvant Chemoradiotherapy ◽  
Lymphatic Vessels ◽  
Cervical Squamous Cell Carcinoma ◽  
Positive Expression

AbstractObjectiveThe aim of this study was to evaluate the expression of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) in cervical cancer and its clinical significance.MethodsImmunohistochemical assay was used to examine the expression of Ang-1/2 and VEGF in tumor tissue from 56 cervical squamous cell carcinoma patients treated with operation only (SCC-O group), as well as 51 subjects with cervical squamous cell carcinoma treated with neoadjuvant radiotherapy (SCC-RCO group, n=28) or neoadjuvant chemotherapy (SCC-CO group, n=23). Both microvessel density (MVD) and lymphatic vessel density (LVD) were examined in the three groups through detection of CD34 and D2-40 expression in respective tissue samples.ResultsWith the progression of cervical cancer, the positive expression scores of Ang-2 and VEGF were significantly increased (p<0.05). Compared with surgical intervention, neoadjuvant chemoradiotherapy significantly reduced the positive expression scores of Ang-1, Ang-2, and VEGF in cervical cancer tissues (p<0.05). The MVD values of the SCC-CO and SCC-RO groups were significantly reduced as compared to the SCC-O group (p<0.05). Similarly, the LVD values of the SCC-CO and SCC-RO groups were also significantly reduced when compared to those of the SCC-O group (p<0.05). However, LVD values of the SCC-CO and SCC-RO groups were not statistical different (p>0.05).ConclusionAng-1, Ang-2 and VEGF may play an important role in the development of cervical cancer. Mutual synergism of Ang-2 and VEGF demonstrated a close relationship with the generation of cervical blood and lymphatic vessels. Cervical cancer radiotherapy and chemotherapy could significantly inhibit the formation of blood vessels and lymphatic vessels in tumor tissue.

scholarly journals Construction and Validation of an Immune-Related Gene Prognostic Index for Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Qinghua Ji ◽  
Yingying Cai ◽  
Sachin Mulmi Shrestha ◽  
Duo Shen ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Index ◽  
Enrichment Analysis ◽  
Response To Therapy ◽  
Gene Set Enrichment Analysis ◽  
Related Gene ◽  
Immune Related Gene

Immune checkpoint inhibitor (ICI) therapy may benefit patients with advanced esophageal squamous cell carcinoma (ESCC); however, novel biomarkers are needed to help predict the response of patients to treatment. Differentially expressed immune-related genes within The Cancer Genome Atlas ESCC dataset were selected using the weighted gene coexpression network and lasso Cox regression analyses. Based on these data, an immune-related gene prognostic index (IRGPI) was constructed. The molecular characteristics of the different IRGPI subgroups were assessed using mutation information and gene set enrichment analysis. Differences in immune cell infiltration and the response to ICI therapy and other drugs were also analyzed. Additionally, tumor and adjacent control tissues were collected from six patients with ESCC and the expression of these genes was verified using real-time quantitative polymerase chain reaction. IRGPI was designed based on CLDN1, HCAR3, FNBP1L, and BRCA2, the expression of which was confirmed in ESCC samples. The prognosis of patients in the high-IRGPI group was poor, as verified using publicly available expression data. KMT2D mutations were more common in the high-IRGPI group. Enrichment analysis revealed an active immune response, and immune infiltration assessment showed that the high-IRGPI group had an increased infiltration degree of CD8 T cells, which contributed to the improved response to ICI treatment. Collectively, these data demonstrate that IRGPI is a robust biomarker for predicting the prognosis and response to therapy of patients with ESCC.

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