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TCGA data ovarian cancer

Ashok Rajaraman, Jian Ma
Integrated analysis of structural variants (SVs) and copy number alterations in aneuploid cancer genomes is key to understanding tumor genome complexity. A recently developed algorithm, Weaver, can estimate, for the first time, allele-specific copy number of SVs and their interconnectivity in aneuploid cancer genomes. However, one major limitation is that not all SVs identified by Weaver are phased. In this article, we develop a general convex programming framework that predicts the interconnectivity of unphased SVs with possibly noisy allele-specific copy number estimations as input...
April 16, 2018: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
R Tyler Hillman, Gary B Chisholm, Karen H Lu, P Andrew Futreal
Background: To identify clinically relevant genomic rearrangement signatures in high-grade serous ovarian cancer (HGSOC), we conducted a retrospective analysis of sequenced HGSOC whole-tumor genomes. Methods: Clinical data and whole-genome sequencing (WGS) reads were obtained for primary HGSOC tumors sequenced by the Australian Ovarian Cancer Study (AOCS; n = 80). Genomic rearrangements were identified, and non-negative matrix factorization (NMF) was used to extract rearrangement signatures...
March 1, 2018: Journal of the National Cancer Institute
Constantinos Roufas, Dimitrios Chasiotis, Anestis Makris, Christodoulos Efstathiades, Christos Dimopoulos, Apostolos Zaravinos
Background: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies...
2018: Frontiers in Oncology
Yu Geng, Zhongmeng Zhao, Xuanping Zhang, Wenke Wang, Xingjian Cui, Kai Ye, Xiao Xiao, Jiayin Wang
BACKGROUND: Identifying rare germline and somatic variants associated with cancer progression is an important research topic in cancer genomics. Although many approaches are proposed for rare variant association study, they are not fit for cancer sequencing data due to multiple issues, such as overly relying on pre-selection, losing sight of interacting hotspots, etc. RESULTS: In this article, we propose an improved pipeline to identify germline variant and somatic mutation interactions influencing cancer susceptibility from pair-wise cancer sequencing data...
October 16, 2017: BMC Genomics
S-H Zou, X Du, F-D Sun, P-C Wang, M Li
OBJECTIVE: To observe the effect of cisplatin-induced autophagy in human ovarian cancer cell lines and explore the correlation between RP11-135L22.1 with cisplatin-induced autophagy. MATERIALS AND METHODS: Genome-wide expression profile and chemotherapy sensitivity data of ovarian cancer were downloaded from TCGA database. It was found that the expression level of lncRNA RP11-135L22.1 differed between chemotherapy-sensitive group and insensitive group. Besides, RP11-135L22...
February 2018: European Review for Medical and Pharmacological Sciences
Xiao-Jiao Li, Jin-Shu Pang, Yao-Mei Li, Farah Abdirahman Ahmed, Rong-Quan He, Jie Ma, Fu-Chao Ma, Gang Chen
OBJECTIVE: An increasing number of studies have confirmed that survivin (BIRC5) plays essential roles in ovarian cancer. Nevertheless, inconsistent or controversial results exist in some studies. In the present study, we sought to determine the clinical significance of survivin and its potential molecular pathways. METHODS: The correlation between survivin (BIRC5) expression and diagnostic value, prognostic value and clinicopathological features was assessed by meta-analysis with more than 4000 patients from literature, GEO and TCGA...
March 2018: Pathology, Research and Practice
Lei Zheng, Li Li, Yun Lu, Fangfang Jiang, Xiu-An Yang
This study is to investigate transcription factors involved in cisplatin resistance in ovarian cancer cells. The transcriptome of cisplatin resistant and sensitive A2780 epithelial ovarian cancer cells was obtained from GSE15372. Ovarian transcriptome data GSE62944 was downloaded from TCGA and applied for transcription regulatory network analysis. The analysis results were confirmed using quantitative polymerase chain reaction. The roles of SREBP2 in cisplatin-resistant cells were investigated by RNA inference and cell viability analysis...
April 2018: Experimental Biology and Medicine
Eunice Carrasquinha, André Veríssimo, Marta B Lopes, Susana Vinga
Background: Survival analysis is a statistical technique widely used in many fields of science, in particular in the medical area, and which studies the time until an event of interest occurs. Outlier detection in this context has gained great importance due to the fact that the identification of long or short-term survivors may lead to the detection of new prognostic factors. However, the results obtained using different outlier detection methods and residuals are seldom the same and are strongly dependent of the specific Cox proportional hazards model selected...
2018: BioData Mining
Q Zhang, W-W Wang, T-H Xu, Z-F Xu
OBJECTIVE: To investigate the expression of long non-coding RNA DUXAP10 in ovarian cancer and its effect on ovarian cancer cell lines HO8910 and A2780 cells. MATERIALS AND METHODS: Search the microarray dataset from the Gene Expression Omnibus (GEO) database using the keywords "ovarian cancer" and "GPL570". The differentially expressed genes in ovarian cancer tissues and normal ovarian tissues were analyzed by bioinformatics. Normal ovarian epithelial cells IOSE386, ovarian cancer HEY, HO8910 and A2780 cell lines were cultured...
January 2018: European Review for Medical and Pharmacological Sciences
Katherine R Miller, Jai N Patel, Qing Zhang, Eric J Norris, James Symanowski, Chad Michener, Jalid Sehouli, Ioana Braicu, Darla D Destephanis, Ashley P Sutker, Wendell Jones, Chad A Livasy, Charles Biscotti, Ram N Ganapathi, David L Tait, Mahrukh K Ganapathi
OBJECTIVES: Aberrant homeobox (HOX) gene expression is reported in high-grade serous ovarian carcinoma (HGSOC), however, its prognostic significance remains unclear. METHODS: HOX genes associated with progression-free survival (PFS) in a discovery cohort of primary HGSOC samples with RNA sequencing data, and those previously reported to be associated with clinical outcomes, were selected for qPCR testing in an independent training cohort of primary HGSOC samples (n=71)...
April 2018: Gynecologic Oncology
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
V Heinzelmann-Schwarz, A Knipprath Mészaros, S Stadlmann, F Jacob, A Schoetzau, K Russell, M Friedlander, G Singer, M Vetter
OBJECTIVES: Endocrine therapy is used as maintenance in estrogen receptor (ER) positive breast cancers and has been proposed in low-grade serous ovarian cancers (LGSOC). Here we examine a rationale for its use as maintenance in high-grade serous ovarian cancers (HGSOC). METHODS: We accessed the TCGA PANCAN dataset to evaluate the expression of ESR1. ESR1 expression data on all cancers (n=8901) and HGSOC (n=527) were followed by investigation of ER expression via immunohistochemistry (IHC) (n=4071)...
January 2018: Gynecologic Oncology
Huifeng Niu, Hyunjin Shin, Feng Gao, Jacob Zhang, Brittany Bahamon, Hadi Danaee, Bohuslav Melichar, Russell J Schilder, Robert L Coleman, Gerald Falchook, Antoine Adenis, Kian Behbakht, Angela DeMichele, Elizabeth Claire Dees, Kimberly Perez, Ursula Matulonis, Piotr Sawrycki, Dirk Huebner, Jeffrey Ecsedy
BACKGROUND: Alisertib (MLN8237) is an investigational, oral, selective Aurora A kinase inhibitor. Aurora A contains two functional single nucleotide polymorphisms (SNPs; codon 31 [F/I] and codon 57 [V/I]) that lead to functional changes. This study investigated the prognostic and predictive significance of these SNPs. METHODS: This study evaluated associations between Aurora A SNPs and overall survival (OS) in The Cancer Genome Atlas (TCGA) database. The Aurora A SNPs were also evaluated as predictive biomarkers for clinical outcomes to alisertib in two phase 2 studies (NCT01045421 and NCT01091428)...
November 2017: EBioMedicine
Tianzhen Wang, Guangyu Wang, Xiaoxiao Zhang, Di Wu, Lei Yang, Guangyou Wang, Dapeng Hao
miRNAs, a class of short but stable noncoding RNA molecules, have been revealed to play important roles in the DNA damage response (DDR). However, their functions in cancer genome instability and the consequent clinical effect as the response to chemotherapy have not been fully elucidated. In this study, we utilized multidimensional TCGA data and the known miRNAs involved in DDR to identify a miRNA-regulatory network that responds to DNA damage. Additionally, based on the expression of ten miRNAs in this network, we developed a 10-miRNA-score that predicts defects in the homologous recombination (HR) pathway and genome instability in ovarian cancer...
November 7, 2017: Scientific Reports
Lianzhi Qin, Ting Li, Yuhua Liu
In this study, we aimed to examine the expression of SLC4A11 in ovarian cancer and in normal ovarian tissues, its prognostic value and the possible mechanism of its dysregulation. Bioinformatic analysis was performed by using data from the GEO datasets, the Cancer Genome Atlas-Ovarian Cancer (TCGA-OV) and the Human Protein Atlas (HPA). Results showed that SLC4A11 was upregulated in ovarian cancer compared with normal ovarian epithelial tissues. In patients with primary serous ovarian cancer in TCGA-OV, the cases with lymphatic invasion (N = 133) had significantly higher SLC4A11 expression than those without lymphatic invasion (N = 77) (p = 0...
2017: PloS One
Xu Meng, Guo Jin-Cheng, Zhang Jue, Ma Quan-Fu, Yan Bin, Wu Xu-Feng
Ovarian cancer is prevalent in women which is usually diagnosed at an advanced stage with a high mortality rate. The aim of this study is to investigate protein-coding gene, long non-coding RNA, and microRNA associated with the prognosis of patients with ovarian serous carcinoma by mining data from TCGA (The Cancer Genome Atlas) public database. The clinical data of ovarian serous carcinoma patients was downloaded from TCGA database in September, 2016. The mean age and survival time of 407 patients with ovarian serous carcinoma were 59...
September 22, 2017: Oncotarget
Nadeem Riaz, Pedro Blecua, Raymond S Lim, Ronglai Shen, Daniel S Higginson, Nils Weinhold, Larry Norton, Britta Weigelt, Simon N Powell, Jorge S Reis-Filho
BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair and are germ-line cancer pre-disposition genes that result in a syndrome of hereditary breast and ovarian cancer (HBOC). Whether germ-line or somatic alterations in these genes or other members of the HR pathway and if mono- or bi-allelic alterations of HR-related genes have a phenotypic impact on other cancers remains to be fully elucidated. Here, we perform a pan-cancer analysis of The Cancer Genome Atlas (TCGA) data set and observe that bi-allelic pathogenic alterations in homologous recombination (HR) DNA repair-related genes are prevalent across many malignancies...
October 11, 2017: Nature Communications
H M Jeong, J Han, S H Lee, H-J Park, H J Lee, J-S Choi, Y M Lee, Y-L Choi, Y K Shin, M J Kwon
Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2), epithelial cell-specific regulators of alternative splicing, are downregulated during the epithelial-mesenchymal transition (EMT). These factors have roles in tumor progression and metastasis in some cancers; however, their expression and function in ovarian cancer (OC) remain unclear. We found that ESRP1 and ESRP2 mRNAs were expressed at higher levels in OC cells than in immortalized ovarian surface epithelial (IOSE) cells, and confirmed their overexpression in OC tissues at the protein level...
October 9, 2017: Oncogenesis
Liyuan Guo, Yan Peng, Yuanyuan Meng, Yunduo Liu, Shangshang Yang, Hong Jin, Qi Li
Emerging evidence shows that dysregulated expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely linked with disease progression, including cancers. However, the joint predictive power of miRNAs and lncRNAs in prognosis for ovarian cancer (OV) patients with wild-type BRCA1/2 is as yet unknown. In this study, we sought to assess the joint predictive power of miRNAs and lncRNAs by integrating miRNA and lncRNA expression profiles and clinical data of 281 OV patients with wild-type BRCA1/2 from The Cancer Genome Atlas (TCGA) project...
September 15, 2017: Oncotarget
Alokkumar Jha, Yasar Khan, Muntazir Mehdi, Md Rezaul Karim, Qaiser Mehmood, Achille Zappa, Dietrich Rebholz-Schuhmann, Ratnesh Sahay
BACKGROUND: Next Generation Sequencing (NGS) is playing a key role in therapeutic decision making for the cancer prognosis and treatment. The NGS technologies are producing a massive amount of sequencing datasets. Often, these datasets are published from the isolated and different sequencing facilities. Consequently, the process of sharing and aggregating multisite sequencing datasets are thwarted by issues such as the need to discover relevant data from different sources, built scalable repositories, the automation of data linkage, the volume of the data, efficient querying mechanism, and information rich intuitive visualisation...
September 19, 2017: Journal of Biomedical Semantics
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