scholarly journals A Human Pan-Cancer System Analysis of Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 3 (PLOD3)

2021 ◽  
Vol 22 (18) ◽  
pp. 9903
Author(s):  
Siming Gong ◽  
Yingjuan Duan ◽  
Changwu Wu ◽  
Georg Osterhoff ◽  
Nikolas Schopow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
System Analysis ◽  
Human Cancer ◽  
Soft Tissue Sarcomas ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cancer Tissue ◽  
Potential Biomarker

The overexpression of the enzymes involved in the degradation of procollagen lysine is correlated with various tumor entities. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) expression was found to be correlated to the progression and migration of cancer cells in gastric, lung and prostate cancer. Here, we analyzed the gene expression, protein expression, and the clinical parameters of survival across 33 cancers based on the Clinical Proteomic Tumor Analysis Consortium (CPTAC), function annotation of the mammalian genome 5 (FANTOM5), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA) and The Cancer Genome Atlas (TCGA) databases. Genetic alteration, immune infiltration and relevant cellular pathways were analyzed in detail. PLOD3 expression negatively correlated with survival periods and the infiltration level of CD8+ T cells, but positively correlated to the infiltration of cancer associated fibroblasts in diverse cancers. Immunohistochemistry in colon carcinomas, glioblastomas, and soft tissue sarcomas further confirm PLOD 3 expression in human cancer tissue. Moreover, amplification and mutation accounted for the largest proportion in esophageal adenocarcinoma and uterine corpus endometrial carcinoma, respectively; the copy number alteration of PLOD3 appeared in all cancers from TCGA; and molecular mechanisms further proved the effect of PLOD3 on tumorigenesis. In particular, PLOD3 expression appears to have a tumor immunological effect, and is related to multiple immune cells. Furthermore, it is also associated with tumor mutation burden and microsatellite instability in various tumors. PLOD3 acts as an inducer of various cancers, and it could be a potential biomarker for prognosis and targeted treatment.

scholarly journals Functions and clinical significance of KLRG1 in the development of lung adenocarcinoma and immunotherapy

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaodong Yang ◽  
Yuexin Zheng ◽  
Zhihai Han ◽  
Xiliang Zhang
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Molecular Mechanisms ◽  
Killer Cell ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Normal Lung ◽  
Using Data ◽  
Low Expression

Abstract Background As a marker of differentiation, Killer cell lectin like receptor G1 (KLRG1) plays an inhibitory role in human NK cells and T cells. However, its clinical role remains inexplicit. This work intended to investigate the predictive ability of KLRG1 on the efficacy of immune-checkpoint inhibitor in the treatment of lung adenocarcinoma (LUAD), as well as contribute to the possible molecular mechanisms of KLRG1 on LUAD development. Methods Using data from the Gene Expression Omnibus, the Cancer Genome Atlas and the Genotype-Tissue Expression, we compared the expression of KLRG1 and its related genes Bruton tyrosine kinase (BTK), C-C motif chemokine receptor 2 (CCR2), Scm polycomb group protein like 4 (SCML4) in LUAD and normal lung tissues. We also established stable LUAD cell lines with KLRG1 gene knockdown and investigated the effect of KLRG1 knockdown on tumor cell proliferation. We further studied the prognostic value of the four factors in terms of overall survival (OS) in LUAD. Using data from the Gene Expression Omnibus, we further investigated the expression of KLRG1 in the patients with different responses after immunotherapy. Results The expression of KLRG1, BTK, CCR2 and SCML4 was significantly downregulated in LUAD tissues compared to normal controls. Knockdown of KLRG1 promoted the proliferation of A549 and H1299 tumor cells. And low expression of these four factors was associated with unfavorable overall survival in patients with LUAD. Furthermore, low expression of KLRG1 also correlated with poor responses to immunotherapy in LUAD patients. Conclusion Based on these findings, we inferred that KLRG1 had significant correlation with immunotherapy response. Meanwhile, KLRG1, BTK, CCR2 and SCML4 might serve as valuable prognostic biomarkers in LUAD.

scholarly journals Tissue, age, sex, and disease patterns of matrisome expression in GTEx transcriptome data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tim O. Nieuwenhuis ◽  
Avi Z. Rosenberg ◽  
Matthew N. McCall ◽  
Marc K. Halushka
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Disease Patterns ◽  
Generalized Matrix ◽  
Gene Transcripts ◽  
Matrix Control

AbstractThe extracellular matrix (ECM) has historically been explored through proteomic methods. Whether or not global transcriptomics can yield meaningful information on the human matrisome is unknown. Gene expression data from 17,382 samples across 52 tissues, were obtained from the Genotype-Tissue Expression (GTEx) project. Additional datasets were obtained from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus for comparisons. Gene expression levels generally matched proteome-derived matrisome expression patterns. Further, matrisome gene expression properly clustered tissue types, with some matrisome genes including SERPIN family members having tissue-restricted expression patterns. Deeper analyses revealed 382 gene transcripts varied by age and 315 varied by sex in at least one tissue, with expression correlating with digitally imaged histologic tissue features. A comparison of TCGA tumor, TCGA adjacent normal and GTEx normal tissues demonstrated robustness of the GTEx samples as a generalized matrix control, while also determining a common primary tumor matrisome. Additionally, GTEx tissues served as a useful non-diseased control in a separate study of idiopathic pulmonary fibrosis (IPF) matrix changes, while identifying 22 matrix genes upregulated in IPF. Altogether, these findings indicate that the transcriptome, in general, and GTEx in particular, has value in understanding the state of organ ECM.

scholarly journals PRINS lncRNA Is a New Biomarker Candidate for HPV Infection and Prognosis of Head and Neck Squamous Cell Carcinomas

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 762
Author(s):  
Magda Kopczyńska ◽  
Tomasz Kolenda ◽  
Kacper Guglas ◽  
Joanna Sobocińska ◽  
Anna Teresiak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Head And Neck ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Hpv Infection ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Data Set ◽  
Potential Biomarker

Numerous studies have shown that human papillomavirus (HPV) infection is one of the important risk factors for head and neck squamous cell carcinoma (HNSCC) progression and affects the expression of multiple genes, which might serve as new biomarkers. This study examines the effects of HPV infection on long non-coding RNA (lncRNA) expression and the immune system, particularly PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). The Cancer Genome Atlas (TCGA) expression data for lncRNA genes and clinical data were analyzed by GraphPad Prism 5/7. The expressions of PRINS, CDKN2B-AS1, TTTY14, TTTY15, MEG3, and H19 were significantly different in HPV-positive and HPV-negative patients. HPV-positive patients with high PRINS expression demonstrated significantly better overall survival (OS) and disease-free survival (DFS). HPV-positive patients with high PRINS expression showed changes in gene expression associated with immune and antiviral responses. A majority of HPV-positive patients with high PRINS expression demonstrated a high number of immune cells within tumors. PRINS expression was significantly associated with HPV-infection HNSCC tumors. Validation of these results using data set from Gene Expression Omnibus (GEO) indicated that PRINS is upregulated in HPV active infections and in “atypical 1 (IR)” HNSCC clusters, negatively influencing patients’ overall survival. Patients with high PRINS expression display different immunological profiles than those with low expression levels. For instance, they have active HPV infection status or are clustered in the “atypical 1 (IR)” subtype of HNSCC which influences both viral infection and patients’ survival. It is likely that PRINS could be used as a potential biomarker for HNSCC patients, but its role is dual. On the one hand, it stimulates patients’ immune response, while on the other it can be favorable in virus replication.

scholarly journals TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues

2021 ◽  
Vol 22 (5) ◽  
pp. 2622
Author(s):  
Áron Bartha ◽  
Balázs Győrffy
Keyword(s):  
Gene Expression ◽  
Statistical Significance ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
Tumor Formation ◽  
The Cancer Genome Atlas ◽  
Altered Expression ◽  
Multiple Tumor ◽  
Therapy Targets ◽  
Analysis Platform

Genes showing higher expression in either tumor or metastatic tissues can help in better understanding tumor formation and can serve as biomarkers of progression or as potential therapy targets. Our goal was to establish an integrated database using available transcriptome-level datasets and to create a web platform which enables the mining of this database by comparing normal, tumor and metastatic data across all genes in real time. We utilized data generated by either gene arrays from the Gene Expression Omnibus of the National Center for Biotechnology Information (NCBI-GEO) or RNA-seq from The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and The Genotype-Tissue Expression (GTEx) repositories. The altered expression within different platforms was analyzed separately. Statistical significance was computed using Mann–Whitney or Kruskal–Wallis tests. False Discovery Rate (FDR) was computed using the Benjamini–Hochberg method. The entire database contains 56,938 samples, including 33,520 samples from 3180 gene chip-based studies (453 metastatic, 29,376 tumorous and 3691 normal samples), 11,010 samples from TCGA (394 metastatic, 9886 tumorous and 730 normal), 1193 samples from TARGET (1 metastatic, 1180 tumorous and 12 normal) and 11,215 normal samples from GTEx. The most consistently upregulated genes across multiple tumor types were TOP2A (FC = 7.8), SPP1 (FC = 7.0) and CENPA (FC = 6.03), and the most consistently downregulated gene was ADH1B (FC = 0.15). Validation of differential expression using equally sized training and test sets confirmed the reliability of the database in breast, colon, and lung cancer at an FDR below 10%. The online analysis platform enables unrestricted mining of the database and is accessible at TNMplot.com.

scholarly journals An independent poor-prognosis subtype of hepatocellular carcinoma based on the tumor microenvironment

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098064
Author(s):  
Junfeng Wang ◽  
Jianying Lou ◽  
Lei Fu ◽  
Qu Jin
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Using Data

Background Hepatocellular carcinoma (HCC) is a highly malignant tumor with a particularly poor prognosis. The tumor microenvironment (TME) is closely associated with tumorigenesis, progression, and treatment. However, the relationship between TME genes and HCC patient prognosis is poorly understood. Methods In this study, we identified two prognostic subtypes based on the TME using data from The Cancer Genome Atlas and Gene Expression Omnibus. The Microenvironment Cell Populations-counter method was used to evaluate immune cell infiltration in HCC. Differentially expressed genes between molecular subtypes were calculated with the Limma package, and clusterProfiler was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses to identify genes related to the independent subtypes. We also integrated mRNA expression data into our bioinformatics analysis. Results We identified 4227 TME-associated genes and 640 genes related to the prognosis of HCC. We defined two major subtypes (Clusters 1 and 2) based on the analysis of TME-associated gene expression. Cluster 1 was characterized by increased expression of immune-associated genes and a worse prognosis than Cluster 2. Conclusions The identification of these HCC subtypes based on the TME provides further insight into the molecular mechanisms and prediction of HCC prognosis.

scholarly journals Sex, age, tissue, and disease patterns of matrisome expression in GTEx transcriptome data

2021 ◽  
Author(s):  
Tim O. Nieuwenhuis ◽  
Avi Z. Rosenberg ◽  
Matthew N. McCall ◽  
Marc K. Halushka
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Normal Tissues ◽  
Disease Patterns ◽  
Cancer Genome Atlas ◽  
Unknown Gene ◽  
Gene Expression Levels

AbstractThe extracellular matrix (ECM) has historically been explored through proteomic methods. Whether or not global transcriptomics can yield meaningful information on the human matrisome is unknown. Gene expression data from 17,382 samples across 52 tissues, were obtained from the Genotype-Tissue Expression (GTEx) project. Additional datasets were obtained from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus for comparisons. Gene expression levels generally recapitulated proteome-derived matrisome expression patterns. Further, matrisome gene expression properly clustered tissue types, with some matrisome genes including SERPIN family members having tissue-restricted expression patterns. Deeper analyses revealed 388 genes varied by age and 222 varied by sex in at least one tissue, with expression correlating with digitally imaged histologic tissue features. A comparison of TCGA tumor, TCGA adjacent normal and GTEx normal tissues demonstrated robustness of the GTEx samples as a generalized control, while also determining a common primary tumor matrisome. Additionally, GTEx tissues served as a useful non-diseased control in a separate study of idiopathic pulmonary fibrosis matrix changes. Altogether, these findings indicate that the transcriptome, in general, and GTEx in particular, has value in understanding the state of organ ECM.

scholarly journals RAP1GAP is a novel marker of trabecular pattern and poor sorafenib treatment response in hepatocellular carcinoma

2021 ◽  
Author(s):  
Xue Wen ◽  
Kunkai Su ◽  
Zhikun Liu ◽  
Sunbin Ling ◽  
Di Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Gene Expression Omnibus ◽  
Trabecular Structure ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Sorafenib Treatment ◽  
Trabecular Pattern ◽  
Geo Database

Abstract Background The trabecular pattern is one of the most common features of hepatocellular carcinoma (HCC). In this study, we aimed to identify the molecular mechanisms underlying different trabecular patterns in HCC, and their interaction with current therapies. Methods To screen potential biomarkers of different trabecular patterns, we first linked gene expression data to haematoxylin and eosin (H&E) images from The Cancer Genome Atlas (TCGA). The Gene Expression Omnibus (GEO) database was used to explore potential targets of sorafenib treatment. Selected candidate biomarkers were further verified by immunohistochemistry, and their relationship with sorafenib efficacy was evaluated in 107 HCC samples with trabecular patterns. Results Analysis of RNA sequencing data from TCGA showed that the increasing number of cells in the trabecular structure correlated with increase in the expression of related signalling pathways—Ras, Rap1, IL17, TNF, AGE-RAGE, oestrogen, toll-like receptor signalling, and ubiquitin-mediated proteolysis—and genes related to response to oxygen levels and neoangiogenesis. In contrast, the expression of bile acid and carton, tryptophan, butanoate, and lipid metabolism-related pathways was reduced. The GEO database showed that RAP1GAP, TOB1, ACO2, and SCNN1D expression levels were selectively up-regulated in sorafenib non-responders. Based on the combined analysis of the two datasets and our previous studies, two candidate biomarkers, RAP1GAP and HIF1α, were selected. Immunohistochemical staining showed that RAP1GAP and HIF1α were expressed in the tumour tissues. Interestingly, RAP1GAP was also expressed in the tumour sinusoids. Overexpression of RAP1GAP in sinusoids were associated with trabecular patterns. Multivariate analysis also showed that RAP1GAP expression in the sinusoid was an independent predictor of progressive free survival (PFS) and overall survival (OS) in response to sorafenib treatment. Conclusions RAP1GAP is an essential microenvironment marker in the trabecular structure of HCC and exhibits an adverse association with outcome in sorafenib treatment.

scholarly journals Prognostic Values of Stabilin-2 in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zhicheng Du ◽  
Pengfei Zhu ◽  
Long Yu ◽  
Kunlun Chen ◽  
Janwen Ye ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Survival Time ◽  
Cox Regression ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Primary Malignancy ◽  
Diagnosis And Prognosis ◽  
Kaplan Meier ◽  
Potential Biomarker

Abstract Background: Hepatocellular carcinoma (HCC) is the primary malignancy of the liver. However, biomarkers for early HCC diagnosis are not available. Stabilin (STAB) proteins are scavenger receptors involved in apoptosis and clearance of hyaluronic acid .The role of STAB in HCC has not been previously explored; therefore, the aim of this study was to assess whether STAB gene expression can be used as a novel HCC biomarker.Materials and Methods: Data on 370 HCC patients in the Cancer Genome Atlas database and 221 patients in the Gene Expression Comprehensive Database were retrieved and analyzed. Kaplan–Meier analysis and Cox regression model were used to calculate median survival time using hazard ratio (HR) and 95% confidence interval (CI). Results: The Gene Expression Omnibus dataset showed that high Stabilin-2（STAB2） expression implies longer overall survival (HR after correction = 0.541; 95% CI, 0.339–0.865; p = 0.0182, after correction p = 0.010) and longer recurrence-free survival time (adjusted HR = 0.554; 95% CI, 0.376-0.816; p = 0.0085, adjusted p = 0.003). Conclusions: STAB2 is a potential biomarker for the diagnosis and prognosis of HCC.

scholarly journals Interpreting the Molecular Mechanisms of Yinchenhao Decoction on Hepatocellular Carcinoma through Absorbed Components Based on Network Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Jijia Sun ◽  
Tao Han ◽  
Tao Yang ◽  
Yunhui Chen ◽  
Jihan Huang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Network Pharmacology ◽  
Cancer Genome Atlas ◽  
Target Set ◽  
Cellular Components ◽  
Coexpression Network Analysis

To investigate the mechanisms through which Yinchenhao decoction (YCHD) inhibits hepatocellular carcinoma (HCC), we analyzed YCHD ingredients absorbed into the bloodstream by using network pharmacology. We conducted a weighted gene coexpression network analysis on gene expression data collected from the Gene Expression Omnibus and The Cancer Genome Atlas databases to derive an HCC gene set; moreover, we used four online prediction system databases to predict the potential targets of YCHD ingredients absorbed into the bloodstream. We discovered that YCHD directly interfered with 17 HCC-related disease targets. Subsequent gene ontology enrichment analyses of these 17 disease targets revealed that YCHD exhibited effects through 17 biological processes, 7 molecular functions, and 9 cellular components. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated 14 pathways through which YCHD inhibits HCC. We observed similar trends in how the 17 small molecules interfered with the key target set. We surmised that YCHD inhibits HCC by regulating inflammatory and metabolic pathways. Network pharmacological analysis of YCHD ingredients absorbed into the bloodstream may provide new insights and serve as a new method for discovering the molecular mechanisms through which YCHD inhibits HCC.

scholarly journals Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 158
Author(s):  
Valentina Condelli ◽  
Giovanni Calice ◽  
Alessandra Cassano ◽  
Michele Basso ◽  
Maria Grazia Rodriquenz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Poor Prognosis ◽  
Cpg Island ◽  
Colon Adenocarcinoma ◽  
Gene Signature ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cpg Island Methylator Phenotype ◽  
Prognostic Information ◽  
Global Methylation

Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.

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