scholarly journals Prognostic And Immunological Implications of BTK Expression In Pan-Cancer

2021 ◽  
Author(s):  
Tao Yang ◽  
Lizheng Hao ◽  
Jian Chen ◽  
Xueying Zhu ◽  
Keyi Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
B Cell Lymphoma ◽  
Gene Set Enrichment Analysis ◽  
Lower Grade ◽  
Cox Analysis ◽  
Pan Cancer

Abstract Background: Cancer poses a serious threat to human health. Clarifying the potential significance of Bruton's tyrosine kinase (BTK)in cancer has potential clinical value. This study examined the prognostic and immunological value of BTK gene expression in pan-cancer.Methods: We evaluated the gene expression of BTK in tumor tissues and normal tissues in different cancers. Survival analysis, including Kaplan–Meier analysis and Cox analysis, were performed to explore the prognostic value of BTK for pan-cancer based on survival data from The Cancer Genome Atlas (TCGA) database. Spearman’s method was conducted to analyze the interrelation between BTK gene expression and tumor mutational burden (TMB)and microsatellite instability (MSI). We explored the association of BTK expression with the tumor microenvironment based on Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm. Co-expression analysis of BTK expression and immune-related genes was performed. We used Gene Set Enrichment Analysis (GSEA) to examine the molecular mechanisms and pathways of BTK in pan-cancer.Results: High BTK expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CSEC), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) was positively correlated with patient prognosis, while high expression of BTK in lymphoid neoplasm diffuse large B cell lymphoma (DLBC), brain lower grade glioma (LGG) and esophageal carcinoma (ESCA) corresponded with a worse prognosis. Cox analysis showed that BTK was closely associated to the prognosis of HNSC, LGG, SKCM and LUAD. BTK expression was correlated with clinical stage, TMB and MSI of 10 types of tumors. In HNSC, LGG, LUAD and SKCM, the expression of BTK was positive correlated with immune and stromal scores. Conclusion: BTK expression can act as a prognostic factor in various cancers, especially in HNSC, LGG, LUAD and SKCM, and this may be from its close association with TMB, MSI and immune cell infiltration.

scholarly journals The Functionalities and Clinical Significance of Tumor-Infiltrating Immune Cells in Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jishuai Zhang ◽  
Haifeng Wang ◽  
Haitao Wu ◽  
Guangliang Qiang
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Natural Killer ◽  
Clinical Significance ◽  
Squamous Cell ◽  
Immune Cells ◽  
Gene Set Enrichment Analysis

Tumor-infiltrating immune cells have been implicated in the tumorigenesis and progression of esophageal squamous cell carcinoma (ESCC). However, the functionalities and clinical significance of immune cells remain largely unveiled. In this study, the gene expression data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were extracted. The relative infiltrating levels were estimated by single-sample gene set enrichment analysis. Some cytotoxic immune cells were attenuated, and resting cytotoxic immune cells were accumulated in ESCC. Remarkably, we also observed that infiltrating levels of macrophage M2 and resting natural killer (NK) cells were increased in nonresponders of CRT, and T cells that had anticancer activities such as activated memory CD4 and T helper 2 (Th2) cells were significantly reduced in ESCC tissues of the nonresponders. Moreover, the high infiltrations of the resting natural killer (NK) and dendritic cell (DC) were observed to result in a shorter overall survival in ESCC. Consistently, high expression of immune checkpoint genes, CTLA4 and HAVCR2, was associated with poor prognosis. Furthermore, STAT5B, a key transcription factor, as well as its target genes, involved in the regulation of T cells, was significantly downregulated in ESCC, especially subgroup I, indicating that downregulation of STAT5B might be associated with reduced T cell-mediated anticancer activity. In conclusion, the present study significantly improved our understanding of the regulatory roles of immune cells in ESCC.

scholarly journals SERPINH1 is a Potential Prognostic Biomarker and Correlated With Immune Infiltration: A Pan-Cancer Analysis

2022 ◽  
Vol 12 ◽  
Author(s):  
Yu Wang ◽  
Weigang Gu ◽  
Weiwei Wen ◽  
Xiaofeng Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Biomarker ◽  
Proteinase Inhibitors ◽  
Pearson Correlation ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Pan Cancer

Background: Serpin peptidase inhibitor clade H, member 1 (SERPINH1) is a gene encoding a member of the serpin superfamily of serine proteinase inhibitors. The upregulated of SERPINH1 was associated with poor prognosis in breast cancer, stomach adenocarcinoma, and esophageal carcinoma. However, the role of SERPINH1 in pan-cancer is largely unexplored.Methods: SERPINH1 expression and the correlation with prognosis in human pan-cancer were analyzed by the Cancer Genome Atlas and the Genotype-Tissue Expression dataset. Pearson correlation analysis was applied to evaluate the role of SERPINH1 expression in tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methyltransferase, and common immunoregulators. Spearman’s correlation test was used to analysis SERPINH1 expression in tumor immune infiltration and infiltrating immune cells via the Tumor Immune Evaluation Resource database. Furtherly, immunohistochemistry staining of SERPINH1 was acquired from the Human Protein Atlas database for validation.Results: SERPINH1 was abnormally expressed in fourteen cancers. The high expression of SERPINH1 significantly reduced the overall survival (OS), disease-specific survival, and progression free interval in eleven cancers. Moreover, SERPINH1 expression was correlated with MMR, MSI, TMB, and DNA methylation in multiple types of cancer. Also, SERPINH1 expression showed strong association with immunoregulators and immune checkpoint markers in testicular germ cell tumors, brain lower grade glioma (LGG), pheochromocytoma and paraganglioma. In addition, SERPINH1 expression was related to immune cell infiltration in multiple cancers, particularly in breast invasive carcinoma, LGG, and liver hepatocellular carcinoma. The result of immunohistochemistry verification shown that SERPINH1 staining was higher in tumor samples than in normal tissue in colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma and cervical squamous cell carcinoma, which was consistent with the result of OS.Conclusion: Overall, these results indicate that SERPINH1 may serve as an important prognostic biomarker and correlate with tumor immunity in human pan-cancer.

scholarly journals Review and screening of key genes in esophageal squamous cell carcinoma

2021 ◽  
Author(s):  
Xizi Sun
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Expression Omnibus ◽  
P53 Signaling

Abstract Esophageal squamous cell carcinoma (ESCC) is the most common type of human esophageal cancer with high mortality due to late stage diagnosis. Efforts have been made to figure out the genetic events underlying its carcinogenesis and progression, but the molecular mechanisms of these processes remain elusive. To identify the candidate genes involved in ESCC, literature about significantly mutated genes (SMGs) was extensively reviewed and gene expression profiles of GSE161533, GSE20347 and GSE77861 were downloaded from the Gene Expression Omnibus (GEO) database. Following the identification of 230 differentially expressed genes (DEGs), hub gene identification was performed by the plug-in MCODE in Cytoscape software. 14 hub genes were identified which were enriched in cell cycle, DNA replication and p53 signaling pathway. In summary, genes mentioned in this study may provide potential targets for treatment and diagnosis of ESCC and help us better understand the pathogenesis and progression of ESCC from genetic perspective.

scholarly journals Microarray Analysis of Serum mRNA in Patients with Head and Neck Squamous Cell Carcinoma at Whole-Genome Scale

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Markéta Čapková ◽  
Jana Šáchová ◽  
Hynek Strnad ◽  
Michal Kolář ◽  
Miluše Hroudová ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Microarray Analysis ◽  
Squamous Cell ◽  
Early Stage ◽  
Expression Patterns ◽  
B Cell Lymphoma ◽  
Neck Squamous Cell Carcinoma

With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey’sPvalue<0.05) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease.

scholarly journals Fifteen mRNA-lncRNA expression-based signature predicted the survival of late-staged head and neck squamous cell carcinoma

2020 ◽  
Vol 40 (7) ◽  
Author(s):  
He Ren ◽  
Huaping Li ◽  
Ping Li ◽  
Yuhui Xu ◽  
Gang Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Median Survival ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
The Other ◽  
Neck Squamous Cell Carcinoma ◽  
Better Than

Abstract Background: Gene expression is necessary for regulation in almost all biological processes, at the same time, it is related to the prognosis for head and neck squamous cell carcinoma (HNSCC). The prognosis of late-staged HNSCC is important because of its guiding significance on the therapy strategies. Methods: In this work, we analyzed the relationship between gene expression and HNSCC in The Cancer Genome Atlas (TCGA) cohort, and optimized the panel with random forest survival analysis. Subsequently, a Cox multivariate regression-based model was developed to predict the clinical outcome of HNSCC. The performance of the model was assayed in the training cohort and validated in another three independent cohorts (GSE41614, E-TABM-302, E-MTAB-1328). The underlying pathways significantly associated with the model were identified. According to the results, patients of low-score group (median survival months: 27.4, 95% CI: 18.2–43) had a significant poor survival than those of high-score group (median survival months: 69.4, 95% CI: 58.7–72.1, P=2.7e-5), and the observation was repeatable in the other validation cohorts. Further analysis revealed that the model performed better than the other clinical indicators and is independent of these indicators. Results: Comparison revealed that the model performed better than existing models for late HNSCC prognosis. Gene set enrichment analysis (GSEA) elucidated that the model was significantly associated with various cell processes and pathways.

scholarly journals Identification and validation of key modules and hub genes associated with the pathological stage of oral squamous cell carcinoma by weighted gene co-expression network analysis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8505 ◽  
Author(s):  
Xuegang Hu ◽  
Guanwen Sun ◽  
Zhiqiang Shi ◽  
Hui Ni ◽  
Shan Jiang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Network Analysis ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Pearson Correlation ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes ◽  
T Stage

Background Oral squamous cell carcinoma (OSCC) is a major lethal malignant cancer of the head and neck region, yet its molecular mechanisms of tumourigenesis are still unclear. Patients and methods We performed weighted gene co-expression network analysis (WGCNA) on RNA-sequencing data with clinical information obtained from The Cancer Genome Atlas (TCGA) database. The relationship between co-expression modules and clinical traits was investigated by Pearson correlation analysis. Furthermore, the prognostic value and expression level of the hub genes of these modules were validated based on data from the TCGA database and other independent datasets from the Gene Expression Omnibus (GEO) database and the Human Protein Atlas database. The significant modules and hub genes were also assessed by functional analysis and gene set enrichment analysis (GSEA). Results We found that the turquoise module was strongly correlated with pathologic T stage and significantly enriched in critical functions and pathways related to tumourigenesis. PPP1R12B, CFD, CRYAB, FAM189A2 and ANGPTL1 were identified and statistically validated as hub genes in the turquoise module and were closely implicated in the prognosis of OSCC. GSEA indicated that five hub genes were significantly involved in many well-known cancer-related biological functions and signaling pathways. Conclusion In brief, we systematically discovered a co-expressed turquoise module and five hub genes associated with the pathologic T stage for the first time, which provided further insight that WGCNA may reveal the molecular regulatory mechanism involved in the carcinogenesis and progression of OSCC. In addition, the five hub genes may be considered candidate prognostic biomarkers and potential therapeutic targets for the precise early diagnosis, clinical treatment and prognosis of OSCC in the future.

scholarly journals Tumor mutation burden (TMB)-associated signature constructed to predict survival of lung squamous cell carcinoma patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dan Yan ◽  
Yi Chen
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Clinical Characteristics ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Risk Scores ◽  
Cox Analysis

AbstractLung squamous cell carcinoma (LUSC) is a common type of lung cancer with high incidence and mortality rate. Tumor mutational burden (TMB) is an emerging biomarker for selecting patients with non-small cell lung cancer (NSCLC) for immunotherapy. This study aimed to reveal TMB involved in the mechanisms of LUSC and develop a model to predict the overall survival of LUSC patients. The information of patients with LUSC were obtained from the cancer genome atlas database (TCGA). Differentially expressed genes (DEGs) between low- and the high-TMB groups were identified and taken as nodes for the protein–protein interaction (PPI) network construction. Gene oncology (GO) enrichment analysis and gene set enrichment analysis (GSEA) were used to investigate the potential molecular mechanism. Then, we identified the factors affecting the prognosis of LUSC through cox analysis, and developed a risk score signature. Kaplan–Meier method was conducted to analyze the difference in survival between the high- and low-risk groups. We constructed a nomogram based on the risk score model and clinical characteristics to predict the overall survival of patients with LUSC. Finally, the signature and nomogram were further validated by using the gene expression data downloaded from the Gene Expression Omnibus (GEO) database. 30 DEGs between high- and low-TMB groups were identified. PPI analysis identified CD22, TLR10, PIGR and SELE as the hub genes. Cox analysis indicated that FAM107A, IGLL1, SELE and T stage were independent prognostic factors of LUSC. Low-risk scores group lived longer than that of patients with high-risk scores in LUSC. Finally, we built a nomogram that integrated the clinical characteristics (TMN stage, age, gender) with the three-gene signature to predict the survival probability of LUSC patients. Further verification in the GEO dataset. TMB might contribute to the pathogenesis of LUSC. TMB-associated genes can be used to develope a model to predict the OS of lung squamous cell carcinoma patients.

scholarly journals The prognostic and clinical significance of IFI44L aberrant downregulation in patients with oral squamous cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Deming Ou ◽  
Ying Wu
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Survival Analysis ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Cox Regression Analysis ◽  
Gene Pairs ◽  
Study Gene Expression

Abstract Background It is a basic task in high-throughput gene expression profiling studies to identify differentially expressed genes (DEGs) between two phenotypes. RankComp, an algorithm, could analyze the highly stable within-sample relative expression orderings (REOs) of gene pairs in a particular type of human normal tissue that are widely reversed in the cancer condition, thereby detecting DEGs for individual disease samples measured by a particular platform. Methods In the present study, Gene Expression Omnibus (GEO) Series (GSE) GSE75540, GSE138206 were downloaded from GEO, by analyzing DEGs in oral squamous cell carcinoma based on online datasets using the RankComp algorithm, using the Kaplan-Meier survival analysis and Cox regression analysis to survival analysis, Gene Set Enrichment Analysis (GSEA) to explore the potential molecular mechanisms underlying. Results We identified 6 reverse gene pairs with stable REOs. All the 12 genes in these 6 reverse gene pairs have been reported to be associated with cancers. Notably, lower Interferon Induced Protein 44 Like (IFI44L) expression was associated with poorer overall survival (OS) and Disease-free survival (DFS) in oral squamous cell carcinoma patients, and IFI44L expression showed satisfactory predictive efficiency by receiver operating characteristic (ROC) curve. Moreover, low IFI44L expression was identified as risk factors for oral squamous cell carcinoma patients’ OS. IFI44L downregulation would lead to the activation of the FRS-mediated FGFR1, FGFR3, and downstream signaling pathways, and might play a role in the PI3K-FGFR cascades. Conclusions Collectively, we identified 6 reverse gene pairs with stable REOs in oral squamous cell carcinoma, which might serve as gene signatures playing a role in the diagnosis in oral squamous cell carcinoma. Moreover, high expression of IFI44L, one of the DEGs in the 6 reverse gene pairs, might be associated with favorable prognosis in oral squamous cell carcinoma patients and serve as a tumor suppressor by acting on the FRS-mediated FGFR signaling.

scholarly journals Identification of Immune Subtypes for Predicting the Prognosis of Patients in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110458
Author(s):  
Jing Sun ◽  
Guiqing Fang ◽  
Zhibin Zuo ◽  
Xijiao Yu ◽  
Lande Xue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Checkpoint ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
The Relationship

Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with poor prognosis and immune response, which plays an important role in tumor progression. Recently, immunotherapies have revolutionized the therapeutic means of malignancies including HNSCC. However, the relationship between immunophenotypes of HNSCC and its clinical response to immune-checkpoint inhibitors remains unclear. We aim to identify molecular subtyping related to distinct immunophenotypes in HNSCC. Consensus clustering algorithm was conducted for subtyping. Immunophenotypes between subtypes were compared according to infiltrating immunocytes, immune reactions, major histocompatibility complex (MHC) family, immunoinhibitory, immunostimulatory and immune scores. The relationship between immunophenotype and genotype was investigated from gene mutation and tumor mutation burden. The potential response of Immune-checkpoint blockade (ICB) therapy was estimated with TIDE and ImmuCellAI algorithms, and immune-checkpoint genes. The immune characteristics were also investigated. Biological functions were annotated by the gene-set enrichment analysis (GSEA) algorithm. Two distinct immune subtypes of HNSCC with different survival outcomes, biological characteristics, immunophenotype, and ICB response were identified. The subtype-1 was featured with better prognosis, more infiltrated immunocytes, stronger immune reaction, higher immune-related gene expression, higher immune-checkpoint gene expression (PD-1, PD-L1, and CTLA-4), and better ICB response. A higher immune response in subtype-1 was also revealed by GSEA. Subtype-1 possessed a higher immune response and more sensitivity to ICB therapy leading to a better prognosis. These findings may shed promising light on the immunotherapy strategy in HNSCC

scholarly journals Bioinformatics-based discovery of PYGM and TNNC2 as potential biomarkers of head and neck squamous cell carcinoma

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Yu Jin ◽  
Ya Yang
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Neck Squamous Cell Carcinoma ◽  
High Morbidity ◽  
Aberrant Expression ◽  
Potential Biomarkers

Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality rates and ranks as the sixth most common cancer all over the world. Despite numerous advancements in therapeutic methods, the prognosis of HNSCC patients still remains poor. Therefore, there is an urgent need to have a better understanding of the molecular mechanisms underlying HNSCC progression and to identify essential genes that could serve as effective biomarkers and potential treatment targets. In the present study, original data of three independent datasets were downloaded from the Gene Expression Omnibus database (GEO) and R language was applied to screen out the differentially expressed genes (DEGs). PYGM and TNNC2 were finally selected from the overlapping DEGs of three datasets for further analyses. Transcriptional and survival data related to PYGM and TNNC2 was detected through multiple online databases such as Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioportal, and UALCAN. Quantitative real-time polymerase chain reaction (qPCR) analysis was adopted for the validation of PYGM and TNNC2 mRNA level in HNSCC tissues and cell lines. Survival curves were plotted to evaluate the association of these two genes with HNSCC prognosis. It was demonstrated that PYGM and TNNC2 were significantly down-regulated in HNSCC and the aberrant expression of PYGM and TNNC2 were correlated with HNSCC prognosis, implying the potential of exploiting them as therapeutic targets for HNSCC treatment or potential biomarkers for diagnosis and prognosis.

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