scholarly journals In Silico Inference of Synthetic Cytotoxic Interactions from Paclitaxel Responses

2021 ◽  
Vol 22 (3) ◽  
pp. 1097
Author(s):  
Jeong Hoon Lee ◽  
Kye Hwa Lee ◽  
Ju Han Kim
Keyword(s):  
Cancer Survival ◽  
Human Cancer ◽  
Survival Rates ◽  
Cumulative Effect ◽  
Suppressor Gene ◽  
The Cancer Genome Atlas ◽  
Prognostic Effect ◽  
Ic50 Values ◽  
Cancer Genome Atlas ◽  
Tp53 Tumor Suppressor Gene

To exploit negatively interacting pairs of cancer somatic mutations in chemotherapy responses or synthetic cytotoxicity (SC), we systematically determined mutational pairs that had significantly lower paclitaxel half maximal inhibitory concentration (IC50) values. We evaluated 407 cell lines with somatic mutation profiles and estimated their copy number and drug-inhibitory concentrations in Genomics of Drug Sensitivity in Cancer (GDSC) database. The SC effect of 142 mutated gene pairs on response to paclitaxel was successfully cross-validated using human cancer datasets for urogenital cancers available in The Cancer Genome Atlas (TCGA) database. We further analyzed the cumulative effect of increasing SC pair numbers on the TP53 tumor suppressor gene. Patients with TCGA bladder and urogenital cancer exhibited improved cancer survival rates as the number of disrupted SC partners (i.e., SYNE2, SON, and/or PRY) of TP53 increased. The prognostic effect of SC burden on response to paclitaxel treatment could be differentiated from response to other cytotoxic drugs. Thus, the concept of pairwise SC may aid the identification of novel therapeutic and prognostic targets.

scholarly journals On the Reproducibility of TCGA Ovarian Cancer MicroRNA Profiles

2013 ◽  
Author(s):  
Ying-Wooi Wan ◽  
Claire Mach ◽  
Genevera I. Allen ◽  
Matthew Anderson ◽  
Zhandong Liu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Survival ◽  
Human Cancer ◽  
The Cancer Genome Atlas ◽  
Detection Algorithms ◽  
Level 3 ◽  
Cancer Genome Atlas ◽  
Ovarian Cancer Survival ◽  
Generation Sequencing

Dysregulated microRNA (miRNA) expression is a well-established feature of human cancer. However, the role of specific miRNAs in determining cancer outcomes remains unclear. Using Level 3 expression data from the Cancer Genome Atlas (TCGA), we identified 61 miRNAs that are associated with overall survival in 469 ovarian cancers profiled by microarray (p<0.01). We also identified 12 miRNAs that are associated with survival when miRNAs were profiled in the same specimens using Next Generation Sequencing (miRNA-Seq) (p<0.01). Surprisingly, only 1 miRNA transcript is associated with ovarian cancer survival in both datasets. Our analyses indicate that this discrepancy is due to the fact that miRNA levels reported by the two platforms correlate poorly, even after correcting for potential issues inherent to signal detection algorithms. Further investigation is warranted.

scholarly journals Elevated ZNF703 Protein Expression Is an Independent Unfavorable Prognostic Factor for Survival of the Patients with Head and Neck Squamous Cell Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Hang Yang ◽  
Wen-Qi Jiang ◽  
Ye Cao ◽  
Yong-An Sun ◽  
Jing Wei ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Head And Neck ◽  
Squamous Cell ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Protein Overexpression ◽  
Prognostic Effect ◽  
Tumor Tissues ◽  
Cancer Genome Atlas

Aim. Data from The Cancer Genome Atlas (TCGA) show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC). However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC.Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC).Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%,P<0.001). ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma) and recurrence (allP<0.05). Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor (P=0.022, hazard ratio = 1.635, 95% CI 1.073–2.493) in HNSCC patients.Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC.

Clinical translation of the cancer genome atlas signature for ovarian cancer survival

2012 ◽  
Vol 125 ◽  
pp. S42
Author(s):  
G. Sfakianos ◽  
E. Iversen ◽  
W. Lowery ◽  
R. Whitaker ◽  
L. Akushevich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Survival ◽  
Cancer Genome ◽  
Clinical Translation ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Ovarian Cancer Survival ◽  
Genome Atlas

scholarly journals ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bai-Quan Qiu ◽  
Xia-Hui Lin ◽  
Song-Qing Lai ◽  
Feng Lu ◽  
Kun Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Prognostic Effect ◽  
Cancer Genome Atlas

Abstract Background Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study. Methods Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells. Results We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes. Conclusion Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.

scholarly journals pyCancerSig: subclassifying human cancer with comprehensive single nucleotide, structural and microsatellite mutational signature deconstruction from whole genome sequencing

2019 ◽  
Author(s):  
Jessada Thutkawkorapin ◽  
Jesper Eisfeldt ◽  
Emma Tham ◽  
Daniel Nilsson
Keyword(s):  
Human Cancer ◽  
The Cancer Genome Atlas ◽  
Driver Mutations ◽  
Learning Technology ◽  
Single Nucleotide ◽  
File Formats ◽  
Learning Technique ◽  
Cancer Genome Atlas ◽  
Python Package ◽  
Non Negative Matrix Factorization

AbstractBackgroundDNA damage accumulates over the course of cancer development. The often-substantial amount of somatic mutations in cancer poses a challenge to traditional methods to characterize tumors based on driver mutations. However, advances in machine learning technology can take advantage of this substantial amount of data.ResultsWe developed a command line interface python package, pyCancerSig, to perform sample profiling by integrating single nucleotide variation (SNV), structural variation (SV) and microsatellite instability (MSI) profiles into a unified profile. It also provides a command to decipher underlying cancer processes, employing an unsupervised learning technique, Non-negative Matrix Factorization, and a command to visualize the results. The package accepts common standard file formats (vcf, bam). The program was evaluated using a cohort of breast- and colorectal cancer from The Cancer Genome Atlas project (TCGA). The result showed that by integrating multiple mutations modes, the tool can correctly identify cases with known clear mutational signatures and can strengthen signatures in cases with unclear signal from an SNV-only profile.ConclusionspyCancerSig has demonstrated its capability in identifying known and unknown cancer processes, and at the same time, illuminates the association within and between the mutation modes.

scholarly journals The Study of the Expression of CGB1 and CGB2 in Human Cancer Tissues

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1082
Author(s):  
Piotr Białas ◽  
Aleksandra Śliwa ◽  
Anna Szczerba ◽  
Anna Jankowska
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Human Cancer ◽  
Germ Cell Tumors ◽  
Lung Squamous Cell Carcinoma ◽  
Cervical Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Cancer Tissues

Human chorionic gonadotropin (hCG) is a well-known hormone produced by the trophoblast during pregnancy as well as by both trophoblastic and non-trophoblastic tumors. hCG is built from two subunits: α (hCGα) and β (hCGβ). The hormone-specific β subunit is encoded by six allelic genes: CGB3, CGB5, CGB6, CGB7, CGB8, and CGB9, mapped to the 19q13.32 locus. This gene cluster also encompasses the CGB1 and CGB2 genes, which were originally considered to be pseudogenes, but as documented by several studies are transcriptionally active. Even though the protein products of these genes have not yet been identified, based on The Cancer Genome Atlas (TCGA) database analysis we showed that the mutual presence of CGB1 and CGB2 transcripts is a characteristic feature of cancers of different origin, including bladder urothelial carcinoma, cervical squamous cell carcinoma, esophageal carcinoma, head and neck squamous cell carcinoma, ovarian serous cystadenocarcinoma, lung squamous cell carcinoma, pancreatic adenocarcinoma, rectum adenocacinoma, testis germ cell tumors, thymoma, uterine corpus endometrial carcinoma and uterine carcinosarcoma.

scholarly journals MTA2 as a Potential Biomarker and Its Involvement in Metastatic Progression of Human Renal Cancer by miR-133b Targeting MMP-9

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1851 ◽  
Author(s):  
Yong-Syuan Chen ◽  
Tung-Wei Hung ◽  
Shih-Chi Su ◽  
Chia-Liang Lin ◽  
Shun-Fa Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Survival Rates ◽  
The Cancer Genome Atlas ◽  
Metastatic Progression ◽  
Tumour Grade ◽  
Potential Biomarker ◽  
Cancer Genome Atlas ◽  
Metalloproteinase 9

Metastasis-associated protein 2 (MTA2) was previously known as a requirement to maintain malignant potentials in several human cancers. However, the role of MTA2 in the progression of renal cell carcinoma (RCC) has not yet been delineated. In this study, MTA2 expression was significantly increased in RCC tissues and cell lines. Increased MTA2 expression was significantly associated with tumour grade (p = 0.002) and was an independent prognostic factor for overall survival with a high RCC tumour grade. MTA2 knockdown inhibited the migration, invasion, and in vivo metastasis of RCC cells without effects on cell proliferation. Regarding molecular mechanisms, MTA2 knockdown reduced the activity, protein level, and mRNA expression of matrix metalloproteinase-9 (MMP-9) in RCC cells. Further analyses demonstrated that patients with lower miR-133b expression had poorer survival rates than those with higher expression from The Cancer Genome Atlas database. Moreover, miR-133b modulated the 3′untranslated region (UTR) of MMP-9 promoter activities and subsequently the migratory and invasive abilities of these dysregulated expressions of MTA2 in RCC cells. The inhibition of MTA2 could contribute to human RCC metastasis by regulating the expression of miR-133b targeting MMP-9 expression.

scholarly journals MicroRNA-Related Prognosis Biomarkers from High-Throughput Sequencing Data of Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xiao-Liang Xing ◽  
Zhi-Yong Yao ◽  
Ti Zhang ◽  
Ning Zhu ◽  
Yuan-Wu Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Differential Expression ◽  
High Throughput Sequencing ◽  
Survival Rates ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
High Throughput Sequencing Data ◽  
Differential Expression Genes ◽  
Cancer Genome Atlas

Background. Colorectal cancer (CRC) is the third most common cancer in the world, and most of them are adenocarcinomas. CRC could be classified as colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ) according to the original tumorigenesis position. Increasing evidences indicated that microRNAs (miRNAs) play an important role in the occurrence of multiple tumors. Methods. In this study, we firstly downloaded miRNA (COAD, 8 controls vs. 455 tumors; READ, 3 controls vs. 161 tumors) and mRNA (COAD, 41 controls vs. 478 tumors; READ, 10 controls vs. 166 tumors) data from The Cancer Genome Atlas (TCGA) database and then used DESeq2, RegParallel, miRDB, TargetScanHuman 7.2, DAVID 6.8, STRING, and Cytoscape software to identify the potential prognosis biomarkers. Results. We identified 175 differential expression miRNAs (DEMs) and 3747 differential expression genes (DEGs) in COAD and 184 DEMs and 3928 DEGs in READ. And then, we obtained 21 (13 in COAD and 8 in READ) DEMs associated with the survival rates, which correlated with 440 (217 in COAD and 223 in READ) overlapping DEGs. Through survival analysis for those overlapping DEGs, we found 11 (8 in COAD and 3 in READ) overlapping DGEs associated with survival rates of patients, which were correlated with 9 (7 in COAD and 2 in READ) DEMs significantly. Conclusion. In this study, we found several candidate prognostic biomarkers which have been identified in various cancers and also found several new prognosis biomarkers of COAD and READ. In conclusion, this analysis based on theoretical knowledge and clinical outcomes we have done needs further confirmation by more researches.

A signature of miRNAs in the blood to help prognosticate prostate cancer at the time of diagnosis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16558-e16558
Author(s):  
Ailsa Roberg Sita-Lumsden ◽  
Damien Leach ◽  
Andrea Zivi ◽  
Mathias Winkler ◽  
Jonathan Waxman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rates ◽  
Benign Prostatic Hypertrophy ◽  
Serum Levels ◽  
The Cancer Genome Atlas ◽  
Circulating Mirnas ◽  
P Values ◽  
Circulating Micrornas ◽  
Cancer Genome Atlas ◽  
Clinically Significant

e16558 Background: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Around 80% of PCas are diagnosed as early, localised stage yet a subset of these will metastasise and eventually prove fatal. Management decisions are based on risk stratification systems. However, these systems are not able to clearly distinguish indolent from aggressive PCa’s and as a result many patients with indolent cancers may be over treated. Circulating microRNAs (miRNA) may be an easily accessible, suitable biomarker to distinguish true indolent from clinically significant early PCas thus reducing overtreatments. Methods: Blood samples from 24 men with benign prostatic hypertrophy (BPH, n = 8), localised PCa (n = 8) or metastatic PCa (n = 8) were collected at time of diagnosis. All men had intact prostates and were naïve to any endocrine or other cancer therapy. A platform of circulating miRNAs were analysed in serum using Abcam FireflyTM technology. Data collected were independently verified using real-time qPCR (Exiqon TM ). The miRNAs identified as being significantly different between groups were then analysed in a published dataset. Results: Serum levels of seven of the miRs examined were significantly different in patients with prostate cancer compared to control across both platforms (miR-10b, miR-125b, miR-210, miR-21, miR-378a, miR-483 and miR93 all with P values < 0.005). A further four miRNAs could differentiate between the benign and metastatic cohorts (miR-126 P = 0.008, miR-150 P = 0.05, miR375 P = 0.007). Kaplein-Meier analysis further identified that the serum levels of four miRNAs showed significant association with survival rates (miR-21 P = 0.032, miR-126 P = 0.032, miR-150 P = 0.032, miR-93 P = 0.019). On examination in a cohort of 280 men from The Cancer Genome Atlas (TCGA), four miRs from the cohort had significantly different expression in patients who eventually relapsed (miR-21 P = 0.048, miR-375 P = 0.021, miR-210 P = 0.0003, miR-93 P = 0.008) Conclusions: Our circulating miRNA based signature could be used to stratify men at prostate cancer diagnosis and help identify those who are likely to harbour micro metastases and would benefit more from an early radical treatment. The data is being validated in larger cohorts.

scholarly journals Involvement of Differentially Expressed microRNAs in the PEGylated Liposome Encapsulated 188Rhenium-Mediated Suppression of Orthotopic Hypopharyngeal Tumor

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3609
Author(s):  
Bing-Ze Lin ◽  
Shen-Ying Wan ◽  
Min-Ying Lin ◽  
Chih-Hsien Chang ◽  
Ting-Wen Chen ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Survival Rates ◽  
Clinical Information ◽  
Hypopharyngeal Cancer ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas ◽  
Cancer Genome Atlas ◽  
Next Generation Sequencing Ngs

Hypopharyngeal cancer (HPC) accounts for the lowest survival rate among all types of head and neck cancers (HNSCC). However, the therapeutic approach for HPC still needs to be investigated. In this study, a theranostic 188Re-liposome was prepared to treat orthotopic HPC tumors and analyze the deregulated microRNA expressive profiles. The therapeutic efficacy of 188Re-liposome on HPC tumors was evaluated using bioluminescent imaging followed by next generation sequencing (NGS) analysis, in order to address the deregulated microRNAs and associated signaling pathways. The differentially expressed microRNAs were also confirmed using clinical HNSCC samples and clinical information from The Cancer Genome Atlas (TCGA) database. Repeated doses of 188Re-liposome were administrated to tumor-bearing mice, and the tumor growth was apparently suppressed after treatment. For NGS analysis, 13 and 9 microRNAs were respectively up-regulated and down-regulated when the cutoffs of fold change were set to 5. Additionally, miR-206-3p and miR-142-5p represented the highest fold of up-regulation and down-regulation by 188Re-liposome, respectively. According to Differentially Expressed MiRNAs in human Cancers (dbDEMC) analysis, most of 188Re-liposome up-regulated microRNAs were categorized as tumor suppressors, while down-regulated microRNAs were oncogenic. The KEGG pathway analysis showed that cancer-related pathways and olfactory and taste transduction accounted for the top pathways affected by 188Re-liposome. 188Re-liposome down-regulated microRNAs, including miR-143, miR-6723, miR-944, and miR-136 were associated with lower survival rates at a high expressive level. 188Re-liposome could suppress the HPC tumors in vivo, and the therapeutic efficacy was associated with the deregulation of microRNAs that could be considered as a prognostic factor.

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