scholarly journals Pan-cancer systematic identification of lncRNAs associated with cancer prognosis

2018 ◽  
Author(s):  
Matthew H. Ung ◽  
Evelien Schaafsma ◽  
Daniel E. Mattox ◽  
George L. Wang ◽  
Chao Cheng
Keyword(s):  
Drug Targets ◽  
Patient Survival ◽  
Cancer Prognosis ◽  
Rna Seq ◽  
Non Coding Rna ◽  
Cancer Types ◽  
Microarray Studies ◽  
Systematic Identification ◽  
Pan Cancer ◽  
Novel Associations

AbstractThe “dark matter” of the genome harbors several non-coding RNA species including IncRNAs, which have been implicated in neoplasias but remain understudied. RNA-seq has provided deep insights into the nature of lncRNAs in cancer but current RNA-seq data are rarely accompanied by longitudinal patient survival information. In contrast, a plethora of microarray studies have collected these clinical metadata that can be leveraged to identify novel associations between gene expression and clinical phenotypes. In this study, we developed an analysis framework that computationally integrates RNA-seq and microarray data to systematically screen 9,463 lncRNAs for association with mortality risk across 20 cancer types. In total, we identified a comprehensive list of associations between lncRNAs and patient survival and demonstrate that these prognostic lncRNAs are under selective pressure and may be functional. Our results provide valuable insights that facilitate further exploration of lncRNAs and their potential as cancer biomarkers and drug targets.

scholarly journals Pan-cancer systematic identification of lncRNAs associated with cancer prognosis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8797 ◽  
Author(s):  
Matthew Ung ◽  
Evelien Schaafsma ◽  
Daniel Mattox ◽  
George L. Wang ◽  
Chao Cheng
Keyword(s):  
Drug Targets ◽  
Patient Survival ◽  
Cancer Prognosis ◽  
Rna Seq ◽  
Non Coding Rna ◽  
Cancer Types ◽  
Non Coding Rnas ◽  
Microarray Studies ◽  
Systematic Identification ◽  
Pan Cancer

Background The “dark matter” of the genome harbors several non-coding RNA species including Long non-coding RNAs (lncRNAs), which have been implicated in neoplasia but remain understudied. RNA-seq has provided deep insights into the nature of lncRNAs in cancer but current RNA-seq data are rarely accompanied by longitudinal patient survival information. In contrast, a plethora of microarray studies have collected these clinical metadata that can be leveraged to identify novel associations between gene expression and clinical phenotypes. Methods In this study, we developed an analysis framework that computationally integrates RNA-seq and microarray data to systematically screen 9,463 lncRNAs for association with mortality risk across 20 cancer types. Results In total, we identified a comprehensive list of associations between lncRNAs and patient survival and demonstrate that these prognostic lncRNAs are under selective pressure and may be functional. Our results provide valuable insights that facilitate further exploration of lncRNAs and their potential as cancer biomarkers and drug targets.

scholarly journals Chromosomal copy number heterogeneity predicts survival rates across cancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erik van Dijk ◽  
Tom van den Bosch ◽  
Kristiaan J. Lenos ◽  
Khalid El Makrini ◽  
Lisanne E. Nijman ◽  
...  
Keyword(s):  
Copy Number ◽  
Cancer Survival ◽  
Survival Rates ◽  
Cancer Prognosis ◽  
Disease Outcomes ◽  
Distinct Disease ◽  
Cancer Types ◽  
Chromosomal Copy Number ◽  
Chromosomal Copy ◽  
Pan Cancer

AbstractSurvival rates of cancer patients vary widely within and between malignancies. While genetic aberrations are at the root of all cancers, individual genomic features cannot explain these distinct disease outcomes. In contrast, intra-tumour heterogeneity (ITH) has the potential to elucidate pan-cancer survival rates and the biology that drives cancer prognosis. Unfortunately, a comprehensive and effective framework to measure ITH across cancers is missing. Here, we introduce a scalable measure of chromosomal copy number heterogeneity (CNH) that predicts patient survival across cancers. We show that the level of ITH can be derived from a single-sample copy number profile. Using gene-expression data and live cell imaging we demonstrate that ongoing chromosomal instability underlies the observed heterogeneity. Analysing 11,534 primary cancer samples from 37 different malignancies, we find that copy number heterogeneity can be accurately deduced and predicts cancer survival across tissues of origin and stages of disease. Our results provide a unifying molecular explanation for the different survival rates observed between cancer types.

scholarly journals A pan-cancer analysis of prognostic genes

PeerJ ◽  
2016 ◽  
Vol 3 ◽  
pp. e1499 ◽  
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.

scholarly journals Characterization of Class-3 Semaphorin Receptors, Neuropilins and Plexins, as Therapeutic Targets in a Pan-Cancer Study

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1816
Author(s):  
Xiaoli Zhang ◽  
Shuai Shao ◽  
Lang Li
Keyword(s):  
Patient Survival ◽  
Cancer Type ◽  
Dependent Manner ◽  
Metastatic Progression ◽  
Drug Responses ◽  
Signal Transducers ◽  
Surface Receptors ◽  
Downstream Signaling ◽  
Cancer Types ◽  
Pan Cancer

Class-3 semaphorins (SEMA3s), initially characterized as axon guidance cues, have been recognized as key regulators for immune responses, angiogenesis, tumorigenesis and drug responses. The functions of SEMA3s are attributed to the activation of downstream signaling cascades mainly mediated by cell surface receptors neuropilins (NRPs) and plexins (PLXNs), yet their roles in human cancers are not completely understood. Here, we provided a detailed pan-cancer analysis of NRPs and PLXNs in their expression, and association with key signal transducers, patient survival, tumor microenvironment (TME), and drug responses. The expression of NRPs and PLXNs were dysregulated in many cancer types, and the majority of them were further dysregulated in metastatic tumors, indicating a role in metastatic progression. Importantly, the expression of these genes was frequently associated with key transducers, patient survival, TME, and drug responses; however, the direction of the association varied for the particular gene queried and the specific cancer type/subtype tested. Specifically, NRP1, NRP2, PLXNA1, PLXNA3, PLXNB3, PLXNC1, and PLXND1 were primarily associated with aggressive phenotypes, whereas the rest were more associated with favorable prognosis. These data highlighted the need to study each as a separate entity in a cancer type- and subtype-dependent manner.

scholarly journals Pan-cancer DNA methylation signature quantification of lifestyle exposures and cancer prognosis

2021 ◽  
Author(s):  
Kangpei Tao ◽  
Jaim Sutton ◽  
James M. Flanagan
Keyword(s):  
Overall Survival ◽  
Alcohol Consumption ◽  
Significant Risk ◽  
B Cell Lymphoma ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Cancer Dataset ◽  
Higher Alcohol ◽  
Cancer Types ◽  
Pan Cancer

Abstract Background: Alcohol consumption, body mass index (BMI) and cigarette smoking are among the most well-studied lifestyle cancer risk exposures which can also change the host’s epigenetic methylation patterns. Some of the changes associated with lifestyle exposure are specific and stable over time, thus, can be used to predict and quantify the exposure. Although the link between these lifestyle exposures and increased odds ratio (OR) of different cancer types is well known, their role in predicting cancer survival remains less clear. We hypothesized that by using predicted lifestyle exposures based on the methylation profiles in tumour DNA we could predict the overall survival probability in cancer patients associated with these exposures. Results: The Cancer Genome Atlas (TCGA) Pan-Cancer dataset was used to test the prognostic value of the predicted DNAmethylation (DNAm) alcohol, BMI and smoking exposures in 24 cancer types (n= 8,238 subjects). Multivariable Cox proportional hazards models with adjustment for age, cancer stage and other exposures were used to calculate the hazards ratio (HR) for overall survival associated with these predicted DNAm exposures. We observed specific cancer types with strong associations between poorer survival and higher alcohol consumption (bladder, brain, esophageal, and head and neck cancers), higher BMI (bladder, pancreatic and post-menopausal breast cancers), and smoking (B-cell lymphoma, stomach, bladder and lung cancers). Interestingly, we also observed associations between better survival from kidney cancer with higher alcohol consumption and smoking exposures. For alcohol consumption we found a positive association between HR and OR across all cancers, indicating that for cancers where alcohol is a significant risk factor, it is also associated with poorer survival (p = 0.022). This was not the case for the BMI (p = 0.548) or smoking exposures (p = 0.193). Conclusions: In conclusion, these DNAm exposure signatures may provide novel information on the relationship between these lifestyle factors and cancer outcomes.

scholarly journals Molecular Mechanisms of PD-1 and PD-L1 Activity on a Pan-Cancer Basis: A Bioinformatic Exploratory Study

2021 ◽  
Vol 22 (11) ◽  
pp. 5478
Author(s):  
Siddarth Kannan ◽  
Geraldine Martina O’Connor ◽  
Emyr Yosef Bakker
Keyword(s):  
Clinical Relevance ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Drug Repurposing ◽  
Immune Checkpoint Blockade ◽  
Multiple Cancers ◽  
Significant Survival ◽  
Cancer Types ◽  
Repurposed Drugs ◽  
Pan Cancer

Immune checkpoint blockade targeting PD-1 (PDCD1)/PD-L1 (CD274) is increasingly used for multiple cancers. However, efficacy and adverse-related events vary significantly. This bioinformatic study interrogated molecular differences pertaining to PDCD1/CD274 and their correlated genes on a pan-cancer basis to identify differences between cancer types. Patient RNA-seq data from fifteen cancer types were accessed on cBioPortal to determine the role of PDCD1/CD274 in patient survival and to identify positively and negatively correlated genes, which were also assessed for clinical relevance. Genes correlating with PDCD1/CD274 across multiple cancers were taken forward for drug repurposing via DRUGSURV and microRNA analysis using miRDB and miRabel. MicroRNAs were also screened for clinical relevance using OncomiR. Forty genes were consistently correlated with PDCD1/CD274 across multiple cancers, with the cancers themselves exhibiting a differential role for the correlated genes in terms of patient survival. Esophageal and renal cancers in particular stood out in this regard as having a unique survival profile. Forty-nine putative microRNAs were identified as being linked to the PDCD1/CD274 network, which were taken forward and further assessed for clinical relevance using OncomiR and previously published literature. One hundred and thirty significant survival associations for 46 microRNAs across fourteen groups of cancers were identified. Finally, a total of 23 putative repurposed drugs targeting multiple components of the PDCD1/CD274 network were identified, which may represent immunotherapeutic adjuvants. Taken together, these results shed light on the varying PDCD1/CD274 networks between individual cancers and signpost a need for more cancer-specific investigations and treatments.

Survey of miRNA-miRNA cooperative regulation principles across cancer types

2018 ◽  
Vol 20 (5) ◽  
pp. 1621-1638 ◽  
Author(s):  
Tingting Shao ◽  
Guangjuan Wang ◽  
Hong Chen ◽  
Yunjin Xie ◽  
Xiyun Jin ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Drug Targets ◽  
System Level ◽  
Modular Architecture ◽  
Scale Free ◽  
Cancer Types ◽  
The Common ◽  
Cancer Network ◽  
Pan Cancer ◽  
Regulatory Landscape

AbstractCooperative regulation among multiple microRNAs (miRNAs) is a complex type of posttranscriptional regulation in human; however, the global view of the system-level regulatory principles across cancers is still unclear. Here, we investigated miRNA-miRNA cooperative regulatory landscape across 18 cancer types and summarized the regulatory principles of miRNAs. The miRNA-miRNA cooperative pan-cancer network exhibited a scale-free and modular architecture. Cancer types with similar tissue origins had high similarity in cooperative network structure and expression of cooperative miRNA pairs. In addition, cooperative miRNAs showed divergent properties, including higher expression, greater expression variation and a stronger regulatory strength towards targets and were likely to regulate cancer hallmark-related functions. We found a marked rewiring of miRNA-miRNA cooperation between various cancers and revealed conserved and rewired network miRNA hubs. We further identified the common hubs, cancer-specific hubs and other hubs, which tend to target known anticancer drug targets. Finally, miRNA cooperative modules were found to be associated with patient survival in several cancer types. Our study highlights the potential of pan-cancer miRNA-miRNA cooperative regulation as a novel paradigm that may aid in the discovery of tumorigenesis mechanisms and development of anticancer drugs.

scholarly journals A Pan-Cancer Study of KMT2 Family as Therapeutic Targets in Cancer

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Jiamin Zhu ◽  
Zhili Liu ◽  
Xiao Liang ◽  
Lu Wang ◽  
Dan Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Microenvironment ◽  
Patient Survival ◽  
Expression Patterns ◽  
Family Members ◽  
Cancer Type ◽  
Tumor Type ◽  
Histone Lysine ◽  
Cancer Types ◽  
Pan Cancer

Objective. Exome sequencing studies have shown that the histone-lysine N-methyltransferase 2 (KMT2) gene is one of the most commonly mutated genes in a range of human malignancies and is linked to some of the most common and deadly solid tumors. However, the connection between this gene family’s function and tumor type, immunological subtype, and molecular subtype dependency is still unknown. Methods. We examine the expression patterns of the histone-lysine N-methyltransferase 2 (KMT2) gene, as well as their relationship to patient survival. We also used a pan-cancer analysis to link their function to immunological subtypes, the tumor microenvironment, and treatment sensitivity. Results. Using the TCGA pan-cancer data, researchers looked at and examined KMT2 expression patterns and their links to patient survival and the tumor microenvironment in 33 cancer types. The expression of the KMT2 family changes significantly across and within cancer types, indicating significant inter- and intracancer heterogeneity. Patients’ overall survival was often linked to the expression of KMT2 family members. However, the direction of the link differed depending on the KMT2 isoform and cancer type studied. Notably, in all cancer types examined, nearly all KMT2 family members were substantially linked with overall survival in patients with renal clear cell carcinoma (KIRC). Furthermore, all KMT2 genes have a strong relationship with immune infiltrate subtypes, as well as varying degrees of stromal cell infiltration and tumor cell stemness. Finally, we discovered that higher expression of KMT2s, particularly KMT2F and KMT2G, was linked to greater chemotherapeutic sensitivity in several cell lines. Conclusions. The necessity to investigate each KMT2 member as a distinct entity inside each particular cancer type is highlighted by our comprehensive investigation of KMT2 gene expression and its relationship with immune infiltrates, tumor microenvironment, and cancer patient outcomes. Our research also confirmed the identification of KMT2 as a potential therapeutic target in cancer, but further laboratory testing is required.

scholarly journals SnoRNA in Cancer Progression, Metastasis and Immunotherapy Response

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 809
Author(s):  
Jildou van der Werf ◽  
Chue Vin Chin ◽  
Nicholas Ian Fleming
Keyword(s):  
Cancer Progression ◽  
Drug Targets ◽  
Cell Function ◽  
Immune Cell ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Cancer Types ◽  
Target Rna ◽  
Nucleolar Rna ◽  
Mtor Signalling

Small nucleolar RNA (snoRNA) were one of our earliest recognised classes of non-coding RNA, but were largely ignored by cancer investigators due to an assumption that their activities were confined to the nucleolus. However, as full genome sequences have become available, many new snoRNA genes have been identified, and multiple studies have shown their functions to be diverse. The consensus now is that many snoRNA are dysregulated in cancers, are differentially expressed between cancer types, stages and metastases, and they can actively modify disease progression. In addition, the regulation of the snoRNA class is dominated by the cancer-supporting mTOR signalling pathway, and they may have particular significance to immune cell function and anti-tumour immune responses. Given the recent advent of therapeutics that can target RNA molecules, snoRNA have robust potential as drug targets, either solely or in the context of immunotherapies.

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