An Integrative Pan-Cancer Analysis of the Oncogenic Role of COPB2 in Human Tumors

Several studies have suggested that coatomer protein complex subunit beta 2 (COPB2) may act as an oncogene in various cancer types. However, no systematic pan-cancer analysis has been performed to date. Therefore, the present study analyzed the potential oncogenic role of COPB2 using TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The majority of the cancer types overexpressed the COPB2 protein, and its expression significantly correlated with tumor prognosis. In certain tumors, such as those found in breast and ovarian tissues, phosphorylated S859 exhibited high expression. It was found that mutations of the COPB2 protein in kidney and endometrial cancers exhibited a significant impact on patient prognosis. It is interesting to note that COPB2 expression correlated with the number of cancer-associated fibroblasts in certain tumors, such as cervical and endocervical cancers and colon adenocarcinomas. In addition, COPB2 was involved in the transport of substances and correlated with chemotherapy sensitivity. This is considered the first pan-tumor study, which provided a relatively comprehensive understanding of the mechanism by which COPB2 promotes cancer growth.

Download Full-text

Prognostic and Immunological Role of Gasdermin E in Pan-Cancer Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.706266 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zheng Zhang ◽

Shuangshuang Zhao ◽

Haizhen Yang ◽

Yanwei Chen ◽

Huahui Feng ◽

...

Keyword(s):

The Cancer Genome Atlas ◽

Survival Prognosis ◽

Cancer Management ◽

Cancer Associated Fibroblast ◽

Cancer Genome Atlas ◽

Cancer Types ◽

Functional Mechanisms ◽

Pan Cancer

Despite accumulating cell- or animal-based experiments providing the relationship between Gasdermin E (GSDME) and human diseases, especially in malignant cancers, no pan-cancer analysis about the function of GSMDE in cancer management can be available up to date. Our research, for the first time, explored the potential carcinogenic role of GSDME across 33 tumors from the public platform of TCGA (The cancer genome atlas) database. GSDME is highly expressed in most malignant cancers, and obvious relationship exists between GSDME level and survival prognosis of cancer patients. The expression of GSDME was statically associated with the cancer-associated fibroblast infiltration in diverse cancer types, such as BLCA, CHOL, GBM, KIRC, LIHC, MESO, STAD, and UCEC. Furthermore, pyroptosis, sensory perception of sound, and defense response to bacterium were involved in the functional mechanisms of GSDME expression from GO analysis. Last but not the least, in vitro experiments were also performed to identify GSDME-induced pyroptosis. Our first pan-cancer analysis of GSDME not only broadens the understanding of the carcinogenic roles of GSDME but also provides a promising therapeutic strategy for benefiting an increasing number of cancerous patients based on GSDME-induced pyroptosis.

Download Full-text

Integrative Histologic and Bioinformatics Analysis of BIRC5/Survivin Expression in Oral Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms19092664 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2664 ◽

Cited By ~ 6

Author(s):

Giuseppe Troiano ◽

Agostino Guida ◽

Gabriella Aquino ◽

Gerardo Botti ◽

Nunzia Losito ◽

...

Keyword(s):

Gene Expression ◽

Survivin Expression ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Poor Overall Survival ◽

Squamous Cells ◽

Nuclear Expression ◽

Cancer Genome Atlas ◽

Cancer Types

Survivin is a well-known protein involved in the inhibition of apoptosis in many different cancer types. The aim of this study was to perform an integrated bioinformatic and histologic analysis in order to study the expression and prognostic role of Survivin and its related gene BIRC5 in oral cancer. Publicly available databases were accessed via Gene Expression Omnibus and Oncomine, in addition raw data from The Cancer Genome Atlas (TCGA) were also obtained in order to analyze the rate of gene mutation, expression and methylation in patients with oral squamous cells carcinoma (OSCC). Immunohistochemistry (IHC) was also performed in order to evaluate the nuclear and cytoplasmic expression of Survivin and their correlation with cell proliferation in samples from OSCC patients. Results of this study revealed that Survivin is rarely mutated in OSCC samples and upregulated when compared to non-cancerous tissue. A negative correlation between the methylation of the island cg25986496 and BIRC5 mRNA expression was detected from TCGA data. IHC staining revealed that cytoplasmic (and not nuclear) expression of Survivin is associated with poor overall survival in OSCC patients, while the nuclear expression correlates with higher proliferation rate. In addition, data from TCGA database revealed that BIRC5 gene expression is an independent prognostic factor for OSCC patients.

Download Full-text

Integrated Dissection of lncRNA-Perturbated Triplets Reveals Novel Prognostic Signatures Across Cancer Types

International Journal of Molecular Sciences ◽

10.3390/ijms21176087 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6087

Author(s):

Yunzhen Wei ◽

Limeng Zhou ◽

Yingzhang Huang ◽

Dianjing Guo

Keyword(s):

Cancer Biology ◽

Noncoding Rna ◽

The Cancer Genome Atlas ◽

Dynamic Changes ◽

Computational Framework ◽

Potential Biomarker ◽

Cancer Genome Atlas ◽

Cancer Types ◽

Tcga Dataset ◽

Pan Cancer

Long noncoding RNA (lncRNA)/microRNA(miRNA)/mRNA triplets contribute to cancer biology. However, identifying significative triplets remains a major challenge for cancer research. The dynamic changes among factors of the triplets have been less understood. Here, by integrating target information and expression datasets, we proposed a novel computational framework to identify the triplets termed as “lncRNA-perturbated triplets”. We applied the framework to five cancer datasets in The Cancer Genome Atlas (TCGA) project and identified 109 triplets. We showed that the paired miRNAs and mRNAs were widely perturbated by lncRNAs in different cancer types. LncRNA perturbators and lncRNA-perturbated mRNAs showed significantly higher evolutionary conservation than other lncRNAs and mRNAs. Importantly, the lncRNA-perturbated triplets exhibited high cancer specificity. The pan-cancer perturbator OIP5-AS1 had higher expression level than that of the cancer-specific perturbators. These lncRNA perturbators were significantly enriched in known cancer-related pathways. Furthermore, among the 25 lncRNA in the 109 triplets, lncRNA SNHG7 was identified as a stable potential biomarker in lung adenocarcinoma (LUAD) by combining the TCGA dataset and two independent GEO datasets. Results from cell transfection also indicated that overexpression of lncRNA SNHG7 and TUG1 enhanced the expression of the corresponding mRNA PNMA2 and CDC7 in LUAD. Our study provides a systematic dissection of lncRNA-perturbated triplets and facilitates our understanding of the molecular roles of lncRNAs in cancers.

Download Full-text

Downstream Neighbor of SON (DONSON) Expression Is Enhanced in Phenotypically Aggressive Prostate Cancers

Cancers ◽

10.3390/cancers12113439 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3439 ◽

Cited By ~ 1

Author(s):

Niklas Klümper ◽

Marthe von Danwitz ◽

Johannes Stein ◽

Doris Schmidt ◽

Anja Schmidt ◽

...

Keyword(s):

Cell Cycle Progression ◽

Locally Advanced ◽

Metastatic Potential ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Prostate Cancers ◽

Migration Capacity

Downstream neighbor of Son (DONSON) plays a crucial role in cell cycle progression and in maintaining genomic stability, but its role in prostate cancer (PCa) development and progression is still underinvestigated. Methods: DONSON mRNA expression was analyzed with regard to clinical-pathological parameters and progression using The Cancer Genome Atlas (TCGA) and two publicly available Gene Expression Omnibus (GEO) datasets of PCa. Afterwards, DONSON protein expression was assessed via immunohistochemistry on a comprehensive tissue microarray (TMA). Subsequently, the influence of a DONSON-knockdown induced by the transfection of antisense-oligonucleotides on proliferative capacity and metastatic potential was investigated. DONSON was associated with an aggressive phenotype in the PCa TCGA cohort, two GEO PCa cohorts, and our PCa TMA cohort as DONSON expression was particularly strong in locally advanced, metastasized, and dedifferentiated carcinomas. Thus, DONSON expression was notably upregulated in distant and androgen-deprivation resistant metastases. In vitro, specific DONSON-knockdown significantly reduced the migration capacity in the PCa cell lines PC-3 and LNCaP, which further suggests a tumor-promoting role of DONSON in PCa. In conclusion, the results of our comprehensive expression analyses, as well as the functional data obtained after DONSON-depletion, lead us to the conclusion that DONSON is a promising prognostic biomarker with oncogenic properties in PCa.

Download Full-text

Novel Insights into Epigenetic Regulation of IL6 Pathway: In Silico Perspective on Inflammation and Cancer Relationship

International Journal of Molecular Sciences ◽

10.3390/ijms221810172 ◽

2021 ◽

Vol 22 (18) ◽

pp. 10172

Author(s):

Saverio Candido ◽

Barbara Maria Rita Tomasello ◽

Alessandro Lavoro ◽

Luca Falzone ◽

Giuseppe Gattuso ◽

...

Keyword(s):

Dna Methylation ◽

Epigenetic Regulation ◽

Computational Analysis ◽

The Cancer Genome Atlas ◽

Post Translational Modifications ◽

Pathway Gene ◽

Cancer Genome Atlas ◽

Cancer Types ◽

Tumor Types

IL-6 pathway is abnormally hyperactivated in several cancers triggering tumor cell growth and immune system inhibition. Along with genomic mutation, the IL6 pathway gene expression can be affected by DNA methylation, microRNAs, and post-translational modifications. Computational analysis was performed on the Cancer Genome Atlas (TCGA) datasets to explore the role of IL6, IL6R, IL6ST, and IL6R transmembrane isoform expression and their epigenetic regulation in different cancer types. IL6 was significantly modulated in 70% of tumor types, revealing either up- or down-regulation in an approximately equal number of tumors. Furthermore, IL6R and IL6ST were downregulated in more than 10 tumors. Interestingly, the correlation analysis demonstrated that only the IL6R expression was negatively affected by the DNA methylation within the promoter region in most tumors. Meanwhile, only the IL6ST expression was extensively modulated by miRNAs including miR-182-5p, which also directly targeted all three genes. In addition, IL6 upregulated miR-181a-3p, mirR-214-3p, miR-18a-5p, and miR-938, which in turn inhibited the expression of IL6 receptors. Finally, the patients’ survival rate was significantly affected by analyzed targets in some tumors. Our results suggest the relevance of epigenetic regulation of IL6 signaling and pave the way for further studies to validate these findings and to assess the prognostic and therapeutic predictive value of these epigenetic markers on the clinical outcome and survival of cancer patients.

Download Full-text

The role of miR-92b in cholangiocarcinoma patients

The International Journal of Biological Markers ◽

10.1177/1724600817751524 ◽

2018 ◽

Vol 33 (3) ◽

pp. 293-300 ◽

Cited By ~ 3

Author(s):

Min-hang Zhou ◽

Hong-wei Zhou ◽

Mo Liu ◽

Jun-zhong Sun

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Gene Expression Omnibus ◽

Cancer Genome ◽

The Cancer Genome Atlas ◽

Positive Regulation ◽

Cancer Genome Atlas ◽

High Level ◽

Genome Atlas

Purpose: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. Methods: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan–Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. Results: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.

Download Full-text

A pan-cancer analysis of prognostic genes

PeerJ ◽

10.7717/peerj.1499 ◽

2016 ◽

Vol 3 ◽

pp. e1499 ◽

Cited By ~ 13

Author(s):

Jordan Anaya ◽

Brian Reon ◽

Wei-Min Chen ◽

Stefan Bekiranov ◽

Anindya Dutta

Keyword(s):

Microarray Data ◽

The Cancer Genome Atlas ◽

Rna Seq ◽

Cancer Pathogenesis ◽

Gene Sets ◽

Protective Genes ◽

Cancer Genome Atlas ◽

Cancer Types ◽

Measure Of Association ◽

Pan Cancer

Numerous studies have identified prognostic genes in individual cancers, but a thorough pan-cancer analysis has not been performed. In addition, previous studies have mostly used microarray data instead of RNA-SEQ, and have not published comprehensive lists of associations with survival. Using recently available RNA-SEQ and clinical data from The Cancer Genome Atlas for 6,495 patients, we have investigated every annotated and expressed gene’s association with survival across 16 cancer types. The most statistically significant harmful and protective genes were not shared across cancers, but were enriched in distinct gene sets which were shared across certain groups of cancers. These groups of cancers were independently recapitulated by both unsupervised clustering of Cox coefficients (a measure of association with survival) for individual genes, and for gene programs. This analysis has revealed unappreciated commonalities among cancers which may provide insights into cancer pathogenesis and rationales for co-opting treatments between cancers.

Download Full-text

Pan-cancer driver copy number alterations identified by joint expression/CNA data analysis

Scientific Reports ◽

10.1038/s41598-020-74276-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Gaojianyong Wang ◽

Dimitris Anastassiou

Keyword(s):

Gene Expression ◽

Copy Number ◽

The Cancer Genome Atlas ◽

Copy Number Alterations ◽

Multiple Cancer ◽

Cancer Driver ◽

Large Gene ◽

Cancer Genome Atlas ◽

Cancer Types ◽

Pan Cancer

Abstract Analysis of large gene expression datasets from biopsies of cancer patients can identify co-expression signatures representing particular biomolecular events in cancer. Some of these signatures involve genomically co-localized genes resulting from the presence of copy number alterations (CNAs), for which analysis of the expression of the underlying genes provides valuable information about their combined role as oncogenes or tumor suppressor genes. Here we focus on the discovery and interpretation of such signatures that are present in multiple cancer types due to driver amplifications and deletions in particular regions of the genome after doing a comprehensive analysis combining both gene expression and CNA data from The Cancer Genome Atlas.

Download Full-text

A pan-cancer analysis based on weighted gene co-expression network analysis identifies the biomarker utility of lamin B1 in human tumors

Cancer Biomarkers ◽

10.3233/cbm-203247 ◽

2021 ◽

pp. 1-17

Author(s):

Youwei Hua ◽

Zhihui He ◽

Xu Zhang

Keyword(s):

Network Analysis ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Free Survival ◽

Lamin B1 ◽

Cancer Genome Atlas ◽

Mrna Binding ◽

Functional Mechanisms ◽

Pan Cancer

Emerging evidence has revealed a relationship between lamin B1 (LMNB1) and several cancers such as cervical cancer, liver cancer, and prostate cancer. But no systematic pan-cancer analysis is available. Little is known about the clinical significance and biomarker utility of LMNB1. In this study, we first revealed the key role of LMNB1 in esophageal carcinoma (ESCA) through weighted gene co-expression network analysis (WGCNA) and disease-free survival (DFS) analysis. Based on this result and the datasets of the cancer genome atlas (TCGA), we explored the biomarker utility of LMNB1 across thirty-three tumors. We found that LMNB1 was highly expressed in most of the cancers and significant associations existed between LMNB1 expression and prognosis of cases of nearly half of the cancers. We also found that LMNB1 expression was associated with the infiltration level of Macrophages M1 and T cells CD4 memory activated in some cancers. Moreover, LMNB1 was mainly involved in the functional mechanisms of MRNA binding, olfactory transduction, and gene silencing. Our study first provides a pan-cancer study of LMNB1, thereby offering a relatively comprehensive understanding of the biomarker utility of LMNB1 across thirty-three tumors.

Download Full-text

Pan-cancer analysis of m5C regulator genes reveals consistent epigenetic landscape changes in multiple cancers

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02342-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yuting He ◽

Xiao Yu ◽

Menggang Zhang ◽

Wenzhi Guo

Keyword(s):

Copy Number Variations ◽

Regulatory Genes ◽

The Cancer Genome Atlas ◽

Cancer Pathogenesis ◽

Cancer Genome Atlas ◽

Cancer Types ◽

Reversible Modification ◽

Regulator Genes ◽

Modified Nucleobases ◽

Pan Cancer

Abstract Background 5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs. Methods Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers. Results After validating m5C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival. Conclusion Our results offered strong evidence and clinical implications for the involvement of m5C regulators.

Download Full-text