Methylation of immune-regulatory cytokine genes and pancreatic cancer outcomes

Aim: Given the immunosuppressive nature of pancreatic cancer, we investigated the relationship between epigenetic modification of immune-regulatory cytokine genes and pancreatic cancer outcomes. Materials & methods: We evaluated DNA methylation of 184 pancreatic tumor samples from The Cancer Genome Atlas for 111 CpG loci in seven cytokine genes: IL10, IL6, IL8, TGFβ1, TGFβ2, TGFβ3 and TNF. We used Cox regression to evaluate the associations between methylation and overall survival, disease-specific survival and disease progression (α = 0.05). Results: Poorer survival was associated with increased methylation in fifteen CpG probes in TGFβ1, TGFβ2, TGFβ3 and TNF. We also detected improved outcomes for three loci in IL10, IL8 and IL6. Conclusion: Epigenetic regulation of cytokine-related gene expression may be associated with pancreatic cancer outcomes.

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Screening and Identifying m6A Regulators as an Independent Prognostic Biomarker in Pancreatic Cancer Based on The Cancer Genome Atlas Database

BioMed Research International ◽

10.1155/2021/5573628 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Bi Lin ◽

Yangyang Pan ◽

Dinglai Yu ◽

Shengjie Dai ◽

Hongwei Sun ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cox Regression ◽

Malignant Tumors ◽

Expression Profiles ◽

Tumor Therapy ◽

Disease Free Survival ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Genome Atlas

Background. Pancreatic cancer is one of the most malignant tumors of the digestive system, and its treatment has rarely progressed for the last two decades. Studies on m6A regulators for the past few years have seemingly provided a novel approach for malignant tumor therapy. m6A-related factors may be potential biomarkers and therapeutic targets. This research is focused on the gene characteristics and clinical values of m6A regulators in predicting prognosis in pancreatic cancer. Methods. In our study, we obtained gene expression profiles with copy number variation (CNV) data and clinical characteristic data of 186 patients with pancreatic cancer from The Cancer Genome Atlas (TCGA) portal. Then, we determined the alteration of m6a regulators and their correlation with clinicopathological features using the log-rank tests, Cox regression model, and chi-square test. Additionally, we validated the prognostic value of m6A regulators in the International Cancer Genome Consortium (ICGC). Results. The results suggested that pancreatic cancer patients with ALKBH5 CNV were associated with worse overall survival and disease-free survival than those with diploid genes. Additionally, upregulation of the writer gene ALKBH5 had a positive correlation with the activation of AKT pathways in the TCGA database. Conclusion. Our study not only demonstrated genetic characteristic changes of m6A-related genes in pancreatic cancer and found a strong relationship between the changes of ALKBH5 and poor prognosis but also provided a novel therapeutic target for pancreatic cancer therapy.

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Screening and Identifying m6A Regulators in Pancreatic Cancer Based on The Cancer Genome Atlas Database

10.21203/rs.3.rs-96939/v1 ◽

2020 ◽

Author(s):

Bi Lin ◽

Hongwei Sun ◽

Dinglai Yu ◽

Yukai Xiang ◽

Jie Zhang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cox Regression ◽

Malignant Tumors ◽

Expression Profiles ◽

Tumor Therapy ◽

Disease Free Survival ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Genome Atlas

Abstract Background: Pancreatic cancer is one of the most malignant tumors of the digestive system and its treatment has rarely progressed for the last two decades. Studies on m6A regulators for the past few years have seemingly provided a novel approach for malignant tumor therapy. m6A-related factors may be potential biomarkers and therapeutic targets. This research is focused on the gene characteristics and clinical values of m6A regulators in predicting prognosis in pancreatic cancer. Methods: In our study, we obtained gene expression profiles with copy number variation (CNV) data and clinical characteristic data of 186 patients with pancreatic cancer from The Cancer Genome Atlas portal (TCGA). Then, we determined the alteration of m6a regulators and their correlation with clinicopathological features using the log-rank tests, Cox regression model, and chi-square test. Results: The results suggested that pancreatic cancer patients with ALKBH5 CNV were associated with worse overall survival and disease-free survival than those with diploid genes. Additionally, upregulation of the writer gene ALKBH5 had a positive correlation with the activation of AKT pathways. Conclusion: Our study not only demonstrated genetic characteristic changes of m6A-related genes in pancreatic cancer and found a strong relationship between the changes of ALKBH5 and poor prognosis but also provided a novel therapeutic target for pancreatic cancer therapy.

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Effect of Different Expression of Immune-Related lncRNA on Colon Adenocarcinoma and Its Relation to Prognosis

BioMed Research International ◽

10.1155/2020/6942740 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Meiwei Mu ◽

Yi Tang ◽

Zheng Yang ◽

Yuling Qiu ◽

Xiaohong Li ◽

...

Keyword(s):

Cox Regression ◽

Colon Adenocarcinoma ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Future Research ◽

Sequencing Data ◽

Tissue Samples ◽

Gene Sets ◽

Cancer Genome Atlas ◽

Immune Related Genes

Objective. To explore the expression of immune-related lncRNAs in colon adenocarcinoma and find out the effect on how these lncRNAs influence the development and prognosis of colon adenocarcinoma. Method. Transcriptome data of colon adenocarcinoma from The Cancer Genome Atlas (TCGA) were downloaded, and gene sets “IMMUNE RESPONSE” and “IMMUNE SYSTEM PROCESS” were sought from the Molecular Signatures Database (MSigDB). The expression of immune-related genes was extracted that were immune-related mRNAs. Then, the immune-related lncRNAs were sought out by utilizing of the above data. Clinical traits were combined with immune-related lncRNAs, so that prognostic-related lncRNAs were identified by Cox regression. Multivariate Cox regression was built to calculate risk scores. Relationships between clinical traits and immune-related lncRNAs were also calculated. Result. A total of 480 colorectal adenocarcinoma patients and 41 normal control patients’ transcriptome sequencing data of tissue samples were obtained from TCGA database. 918 immune-related lncRNAs were screened. Cox regression showed that 34 immune-related lncRNAs were associated with colon adenocarcinoma prognosis. Seven lncRNAs were independent risk factors. Conclusion. This study revealed that some lncRNAs can affect the development and prognosis of colon adenocarcinoma. It may provide new theory evidence of molecular mechanism for the future research and molecular targeted therapy of colon adenocarcinoma.

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Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer

Future Oncology ◽

10.2217/fon-2020-1163 ◽

2021 ◽

Author(s):

Xiao-Cheng Wang ◽

Ya Liu ◽

Fei-Wu Long ◽

Liang-Ren Liu ◽

Chuan-Wen Fan

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Prognostic Markers ◽

The Cancer Genome Atlas ◽

Prognostic Signature ◽

Free Survival ◽

Cancer Genome Atlas ◽

Bioinformatic Approaches ◽

Cell Phenotypes ◽

The Relationship

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

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GALNT14 expression in renal clear cell carcinoma and its effect on prognosis

10.21203/rs.3.rs-761157/v1 ◽

2021 ◽

Author(s):

Yuqin Wei ◽

Fan Wu ◽

Shengfeng Zhang ◽

Yanlin Tan ◽

Qunying Wu ◽

...

Keyword(s):

Cell Carcinoma ◽

Cox Regression ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Regulatory Pathways ◽

Cox Analysis ◽

The Relationship

Abstract Background The expression of GALNT14 in kidney renal clear cell carcinoma (KIRC) and its clinical significance remains unknown. Methods The KIRC data expressed by GALNT14 was downloaded from The Cancer Genome Atlas (TCGA) database. The expression of GALNT14 was analyzed by R software, Perl software and online analysis database. The relationship between GALNT14 expression and clinicopathological features in KIRC was analyzed by univariate, multivariate Cox regression and some databases. Gene Expression Profling Interactive Analysis (GEPIA), Starbase v3.0, UALCAN, and Kaplan-Meier were used to analyze the relationship between GALNT14 expression and overall survival (OS) in KIRC. UALCAN detects the expression of GALNT14 methylation in KIRC. Linkedomics and Genemania were used to analyze the gene co-expression of GALNT14. Gene Set Enrichment Analysis (GSEA) was performed to search for potential regulatory pathways. Results We found that GALNT14 was overexpressed in KIRC (p=1.433e-25). Patients with high GALNT14 expression in KIRC had a better prognosis than patients with low GALNT14 expression (p=0.008). In addition, high GALNT14 expression in KIRC was significantly associated with low T stage and positive OS (p<0.05). Univariate Cox analysis showed that GALNT14 was positively correlated with OS (p<0.001). Multivariate Cox analysis showed that GALNT14 was associated with OS (p<0.001), age (p=0.01) and histological grade (p=0.02). GALNT14 methylation is low expressed in KIRC (p<0.001). GSEA analysis showed that GALNT14 was enriched in histidine metabolism, peroxisome, and renin-angiotensin system pathways. Conclusion GALNT14 can be used as an independent prognostic factor for renal clear cell carcinoma and a potential target for clinical diagnosis and treatment of KIRC.

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CYSTM1: A Novel Biomarker for Hepatocellular Carcinoma Prognosis

10.21203/rs.3.rs-150866/v1 ◽

2021 ◽

Author(s):

Jun Du ◽

Jinguo Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Early Stage ◽

Human Tumor ◽

The Cancer Genome Atlas ◽

Data Set ◽

Kaplan Meier ◽

Cancer Genome Atlas ◽

Cox Proportional Hazard Regression ◽

The Relationship

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.

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Opposite Roles of BAP1 in Overall Survival of Uveal Melanoma and Cutaneous Melanoma

Journal of Clinical Medicine ◽

10.3390/jcm9020411 ◽

2020 ◽

Vol 9 (2) ◽

pp. 411 ◽

Cited By ~ 2

Author(s):

Feng Liu-Smith ◽

Yunxia Lu

Keyword(s):

Overall Survival ◽

Uveal Melanoma ◽

Cutaneous Melanoma ◽

Cox Regression ◽

Enrichment Analysis ◽

Copy Number Variations ◽

The Cancer Genome Atlas ◽

Small Subset ◽

Mrna Levels ◽

Cancer Genome Atlas

Background: BRCA1-Associated Protein 1 (BAP1) germline mutations predispose individuals to cancers, including uveal melanoma (UM) and cutaneous melanoma (CM). BAP1 loss is common in UM and is associated with a worse prognosis. BAP1 loss is rare in CM and the outcome is unclear. Methods: UM and CM data was retrieved from The Cancer Genome Atlas (TCGA) database. Cox regression model was performed to examine whether BAP1 mRNA levels or copy number variations were associated with overall survival (OS). Results: BAP1-low mRNA predicted a poor OS in UM (HR = 9.57, 95% CI: 2.82, 32.5) but a contrasting better OS in CM (HR = 0.73, 95% CI: 0.56, 0.95). These results remained unchanged after adjusting for sex, age, and stage in UM and CM, or after adjusting for ulceration or Breslow depth in CM. Additionally, low BAP1 mRNA predicted a better OS in CM patients older than 50 years but not in younger patients. Co-expression and enrichment analysis revealed differential genes and mutations that were correlated with BAP1 expression levels in UM and CM tumors. Conclusions: Low BAP1 mRNA was significantly associated with a better OS in CM patients, in sharp contrast to UM. High BAP1 expression in CM was significantly associated with over-expressed CDK1, BCL2, and KIT at the protein level which may explain the poor OS in this sub-group of patients. Function of BAP1 was largely different in CM and UM despite of a small subset of shared co-expressed genes.

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The Prediction and Prognostic Significance of INPP5K Expression in Patients with Liver Cancer

BioMed Research International ◽

10.1155/2020/9519235 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Ruobing Wang ◽

Yan Jiao ◽

Yanqing Li ◽

Siyang Ye ◽

Guoqiang Pan ◽

...

Keyword(s):

Liver Cancer ◽

Mrna Expression ◽

Poor Prognosis ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Inositol Polyphosphate ◽

Chi Square ◽

Cancer Genome Atlas ◽

Poor Outcomes ◽

The Relationship

Liver cancer is a devastating disease for humans with poor prognosis. Although the survival rate of patients with liver cancer has improved in the past decades, the recurrence and metastasis of liver cancer are still obstacles for us. Inositol polyphosphate-5-phosphatase K (INPP5K) belongs to the family of phosphoinositide 5-phosphatases (PI 5-phosphatases), which have been reported to be associated with cell migration, polarity, adhesion, and cell invasion, especially in cancers. However, there have been few studies on the correlation of INPP5K and liver cancer. In this study, we explored the prognostic significance of INPP5K in liver cancer through bioinformatics analysis of data collected from The Cancer Genome Atlas (TCGA) database. Chi-square and Fisher exact tests were used to evaluate the relationship between INPP5K expression and clinical characteristics. Our results showed that low INPP5K expression was correlated with poor outcomes in liver cancer patients. Univariate and multivariate Cox analyses demonstrated that low INPP5K mRNA expression played a significant role in shortening overall survival (OS) and relapse-free survival (RFS), which might serve as the useful biomarker and prognostic factor for liver cancer. In conclusion, low INPP5K mRNA expression is an independent risk factor for poor prognosis in liver cancer.

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Identification of Hub Prognosis-Associated Oxidative Stress Genes in Pancreatic Cancer Using Integrated Bioinformatics Analysis

Frontiers in Genetics ◽

10.3389/fgene.2020.595361 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xin Qiu ◽

Qin-Han Hou ◽

Qiu-Yue Shi ◽

Hai-Xing Jiang ◽

Shan-Yu Qin

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Pancreatic Cancer ◽

Cancer Progression ◽

Risk Model ◽

Cox Regression ◽

Expression Profiles ◽

The Cancer Genome Atlas ◽

Differentially Expressed ◽

Cox Regression Analysis

BackgroundIntratumoral oxidative stress (OS) has been associated with the progression of various tumors. However, OS has not been considered a candidate therapeutic target for pancreatic cancer (PC) owing to the lack of validated biomarkers.MethodsWe compared gene expression profiles of PC samples and the transcriptome data of normal pancreas tissues from The Cancer Genome Atlas (TCGA) and Genome Tissue Expression (GTEx) databases to identify differentially expressed OS genes in PC. PC patients’ gene profile from the Gene Expression Omnibus (GEO) database was used as a validation cohort.ResultsA total of 148 differentially expressed OS-related genes in PC were used to construct a protein-protein interaction network. Univariate Cox regression analysis, least absolute shrinkage, selection operator analysis revealed seven hub prognosis-associated OS genes that served to construct a prognostic risk model. Based on integrated bioinformatics analyses, our prognostic model, whose diagnostic accuracy was validated in both cohorts, reliably predicted the overall survival of patients with PC and cancer progression. Further analysis revealed significant associations between seven hub gene expression levels and patient outcomes, which were validated at the protein level using the Human Protein Atlas database. A nomogram based on the expression of these seven hub genes exhibited prognostic value in PC.ConclusionOur study provides novel insights into PC pathogenesis and provides new genetic markers for prognosis prediction and clinical treatment personalization for PC patients.

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Cyclin-Dependent Kinase and Antioxidant Gene Expression in Cancers with Poor Therapeutic Response

Pharmaceuticals ◽

10.3390/ph13020026 ◽

2020 ◽

Vol 13 (2) ◽

pp. 26

Author(s):

George S. Scaria ◽

Betsy T. Kren ◽

Mark A. Klein

Keyword(s):

Hepatocellular Carcinoma ◽

Pancreatic Cancer ◽

Antioxidant Defense ◽

Treatment Strategies ◽

The Cancer Genome Atlas ◽

Cyclin Dependent Kinase ◽

Critical Pathways ◽

Cancer Genome Atlas ◽

Antioxidant Gene Expression ◽

Pan Cancer

Pancreatic cancer, hepatocellular carcinoma (HCC), and mesothelioma are treatment-refractory cancers, and patients afflicted with these cancers generally have a very poor prognosis. The genomics of these tumors were analyzed as part of The Cancer Genome Atlas (TCGA) project. However, these analyses are an overview and may miss pathway interactions that could be exploited for therapeutic targeting. In this study, the TCGA Pan-Cancer datasets were queried via cBioPortal for correlations among mRNA expression of key genes in the cell cycle and mitochondrial (mt) antioxidant defense pathways. Here we describe these correlations. The results support further evaluation to develop combination treatment strategies that target these two critical pathways in pancreatic cancer, hepatocellular carcinoma, and mesothelioma.

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