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https://www.readbyqxmd.com/read/29163851/checkpoint-inhibitors-in-endometrial-cancer-preclinical-rationale-and-clinical-activity
#1
REVIEW
Gloria Mittica, Eleonora Ghisoni, Gaia Giannone, Massimo Aglietta, Sofia Genta, Giorgio Valabrega
Context: Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163805/thymine-dna-glycosylase-tdg-is-involved-in-the-pathogenesis-of-intestinal-tumors-with-reduced-apc-expression
#2
Jinfei Xu, Salvatore Cortellino, Rossella Tricarico, Wen-Chi Chang, Gabrielle Scher, Karthik Devarajan, Michael Slifker, Robert Moore, Maria Rosaria Bassi, Elena Caretti, Margie Clapper, Harry Cooper, Alfonso Bellacosa
Thymine DNA Glycosylase (TDG) is a base excision repair enzyme that acts as a thymine and uracil DNA N-glycosylase on G:T and G:U mismatches, thus protecting CpG sites in the genome from mutagenesis by deamination. In addition, TDG has an epigenomic function by removing the novel cytosine derivatives 5-formylcytosine and 5-carboxylcytosine (5caC) generated by Ten-Eleven Translocation (TET) enzymes during active DNA demethylation. We and others previously reported that TDG is essential for mammalian development...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29162923/overexpression-of-suppressive-micrornas-mir-30a-and-mir-200c-are-associated-with-improved-survival-of-breast-cancer-patients
#3
Tsutomu Kawaguchi, Li Yan, Qianya Qi, Xuan Peng, Emmanuel M Gabriel, Jessica Young, Song Liu, Kazuaki Takabe
Some microRNAs (miRNAs) are known to suppress breast cancer. However, whether the expressions of these tumor suppressive miRNAs translate to patient survival were not investigated in large cohort. Nine miRNAs (miR-30a, miR-30c, miR-31, miR-126, miR-140, miR-146b, miR-200c, miR-206, and miR-335) known to be tumor suppressive miRNAs in breast cancer were investigated in Genomic Data Common data portal miRNA-Seq dataset and The Cancer Genome Atlas (TCGA) (n = 1052). Of the 9 miRNAs, miR-30a, miR-30c, miR-126, miR-140, miR-206, and miR-335 were found to have significantly lower expression in breast cancer tissues compared to paired normal breast tissue...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162841/detection-of-somatic-mutations-in-exome-sequencing-of-tumor-only-samples
#4
Yu-Chin Hsu, Yu-Ting Hsiao, Tzu-Yuan Kao, Jan-Gowth Chang, Grace S Shieh
Due to lack of normal samples in clinical diagnosis and to reduce costs, detection of small-scale mutations from tumor-only samples is required but remains relatively unexplored. We developed an algorithm (GATKcan) augmenting GATK with two statistics and machine learning to detect mutations in cancer. The averaged performance of GATKcan in ten experiments outperformed GATK in detecting mutations of randomly sampled 231 from 241 TCGA endometrial tumors (EC). In external validations, GATKcan outperformed GATK in TCGA breast cancer (BC), ovarian cancer (OC) and melanoma tumors, in terms of Matthews correlation coefficient (MCC) and precision, where MCC takes both sensitivity and specificity into account...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162825/outcomes-of-patients-with-sarcoma-enrolled-in-clinical-trials-of-pazopanib-combined-with-histone-deacetylase-mtor-her2-or-mek-inhibitors
#5
Vikas Dembla, Roman Groisberg, Ken Hess, Siqing Fu, Jennifer Wheler, David S Hong, Filip Janku, Ralph Zinner, Sarina Anne Piha-Paul, Vinod Ravi, Robert S Benjamin, Shreyaskumar Patel, Neeta Somaiah, Cynthia E Herzog, Daniel D Karp, Jason Roszik, Funda Meric-Bernstam, Vivek Subbiah
Pazopanib is US FDA approved for the treatment of advanced soft tissue sarcomas. All patients with this disease ultimately develop resistance to therapy. Mechanisms of resistance include activation of the mTOR, histone deacetylase (HDAC), MAPK, and ERBB4 pathways. We hypothesized that combining pazopanib with other targeted agents inhibiting these pathways would increase response rates. We retrospectively evaluated the safety and efficacy of pazopanib plus vorinostat, everolimus, lapatinib or trastuzumab, and MEK inhibitor in patients with advanced sarcoma...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29160179/the-miage-calculator-a-dna-methylation-based-mitotic-age-calculator-of-human-tissue-types
#6
Ahrim Youn, Shuang Wang
Cell division is important in human aging and cancer. To estimate the number of cell divisions (mitotic age) of a given tissue type between individuals is of great interest as that not only allows to study biological aging using a new molecular aging target but also allows the stratification of prospective cancer risk. Here we introduce the MiAge Calculator, a mitotic age calculator based on a novel statistical framework, the MiAge model. MiAge is designed to quantitatively estimate mitotic age (total number of lifetime cell divisions) of a tissue using the stochastic replication errors accumulated in the epigenetic inheritance process during cell divisions...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29158991/ndufa4l2-is-associated-with-clear-cell-renal-cell-carcinoma-malignancy-and-is-regulated-by-elk1
#7
Lei Wang, Zhiqiang Peng, Kaizhen Wang, Yijun Qi, Ying Yang, Yue Zhang, Xinyuan An, Shudong Luo, Junfang Zheng
Background: Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. However, its pathogenesis has not been fully understood till now, which hinders the therapeutic development of ccRCC. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) was found to be upregulated and play an important role in ccRCC. We aimed to further investigate the underlying mechanisms by which NDUFA4L2 exerted function and its expression level was upregulated...
2017: PeerJ
https://www.readbyqxmd.com/read/29158988/a-16-gene-signature-predicting-prognosis-of-patients-with-oral-tongue-squamous-cell-carcinoma
#8
Zeting Qiu, Wei Sun, Shaowei Gao, Huaqiang Zhou, Wulin Tan, Minghui Cao, Wenqi Huang
Background: Oral tongue squamous cell carcinoma (OTSCC) is the most common subtype of oral cancer. A predictive gene signature is necessary for prognosis of OTSCC. Methods: Five microarray data sets of OTSCC from the Gene Expression Omnibus (GEO) and one data set from The Cancer Genome Atlas (TCGA) were obtained. Differentially expressed genes (DEGs) of GEO data sets were identified by integrated analysis. The DEGs associated with prognosis were screened in the TCGA data set by univariate survival analysis to obtain a gene signature...
2017: PeerJ
https://www.readbyqxmd.com/read/29157627/letrozole-may-be-a-valuable-maintenance-treatment-in-high-grade-serous-ovarian-cancer-patients
#9
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)...
November 17, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29156759/smoking-and-gender-modify-the-effect-of-twist-on-patient-survival-in-head-and-neck-squamous-carcinoma
#10
Yun Zhu, Wenjuan Zhang, Ping Wang
Purpose: TWIST is a critical factor for predicting prognosis in several human cancers. Here, we study the prognostic significance of TWIST1 and TWIST2 in Head and Neck squamous cell carcinoma (HNSCC) as well as interactions of TWISTs with both gender and smoking in patient survival. Methods: upper quartile normalized RNA-seq V2 RSEM values of TWIST1 and TWIST2 expressions were retrieved from a TCGA HNSCC dataset. Kaplan-Meier survival curves were used to assess the associations of TWIST1 and TWIST2 with patient survival, and multivariate Cox proportional hazards regression models were used to estimate the hazards ratios (HRs) and their 95% confidence intervals (CIs)...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156748/association-of-melatonin-membrane-receptor-1a-1b-gene-polymorphisms-with-the-occurrence-and-metastasis-of-hepatocellular-carcinoma
#11
Shih-Chi Su, Yung-Chuan Ho, Yu-Fan Liu, Russel J Reiter, Chia-Hsuan Chou, Chia-Ming Yeh, Hsiang-Lin Lee, Wen-Hung Chung, Ming-Ju Hsieh, Shun-Fa Yang
Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by MTNR1A) and 1B (MTNR1B). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156733/an-integrated-lncrna-microrna-and-mrna-signature-to-improve-prognosis-prediction-of-colorectal-cancer
#12
Yongfu Xiong, Rong Wang, Linglong Peng, Wenxian You, Jinlai Wei, Shouru Zhang, Xingye Wu, Jinbao Guo, Jun Xu, Zhenbing Lv, Zhongxue Fu
Although the outcome of patients with colorectal cancer (CRC) has improved significantly, prognosis evaluation still presents challenges due to the disease heterogeneity. Increasing evidences revealed the close correlation between aberrant expression of certain RNAs and the prognosis. We envisioned that combined multiple types of RNAs into a single classifier could improve postoperative risk classification and add prognostic value to the current stage system. Firstly, differentially expressed RNAs including mRNAs, miRNAs and lncRNAs were identified by two different algorithms...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156709/using-molecular-functional-networks-to-manifest-connections-between-obesity-and-obesity-related-diseases
#13
Jialiang Yang, Jing Qiu, Kejing Wang, Lijuan Zhu, Jingjing Fan, Deyin Zheng, Xiaodi Meng, Jiasheng Yang, Lihong Peng, Yu Fu, Dahan Zhang, Shouneng Peng, Haiyun Huang, Yi Zhang
Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152610/mutations-in-coagulation-factor-viii-are-associated-with-more-favorable-outcome-in-patients-with-cutaneous-melanoma
#14
Zheng Ping, Abha Soni, Lance A Williams, Huy P Pham, Malay K Basu, X Long Zheng
Coagulation factor VIII (FVIII), von Willebrand factor (VWF), and ADAMTS13 play an important role in regulation of normal hemostasis. However, little is known about their roles in patients with malignancy, particularly with cutaneous melanoma. Whole genome sequencing data are available for 25,719 cases in 126 cancer genomic studies for analysis. All sequencing data and corresponding pathology findings were obtained from The Cancer Genome Atlas. The cBioportal bioinformatics tools were used for the data analysis...
July 2017: TH Open
https://www.readbyqxmd.com/read/29152124/identification-of-a-sixteen-microrna-signature-as-prognostic-biomarker-for-stage-ii-and-iii-colon-cancer
#15
Havjin Jacob, Luka Stanisavljevic, Kristian Eeg Storli, Kjersti E Hestetun, Olav Dahl, Mette P Myklebust
Despite advances in colon cancer research and novel therapies, high risk of recurrence remains a major challenge. This study reports miRNA expression profiling as a biomarker for the prognosis of TNM stage II and III colon cancer. Fresh frozen biopsies from the study cohort (N=111) were analyzed for miRNA by RT-qPCR and LASSO regression analysis was used to build a classifier of miRNAs. The prognostic accuracy was tested and the classifier was validated in an independent colon cohort (TCGA-COAD, N=209). The LASSO regression analysis identified a 16-miRNA signature including miR-143-5p, miR-27a-3p, miR-31-5p, miR-181a-5p, miR-30b-5p, miR-30d-5p, miR-146a-5p, miR-23a-3p, miR-150-5p, miR-210-3p, miR-25-3p, miR-196a-5p, miR-148a-3p, miR-222-3p, miR-30c-5p and miR-223-3p...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152119/a-genome-wide-comprehensively-analyses-of-long-noncoding-rna-profiling-and-metastasis-associated-lncrnas-in-renal-cell-carcinoma
#16
Xue Xu, Yongcan Xu, Chuanqin Shi, Baoyu Wang, Xiang Yu, Yanfen Zou, Tao Hu
Recently, a growing number of studies have indicated that long noncoding RNAs (lncRNAs) are emerging as new critical regulators of tumorigenesis and prognostic markers in multiple cancers. However, the expression pattern of lncRNAs and their contributions in renal cell carcinoma (RCC) remains poorly understood. In this study, we performed a genome-wide comprehensively analysis of lncRNAs profiling and clinical relevance to provide valuable lncRNA candidates for the further study in RCC. RCC and non-tumor tissues RNA sequencing data, and microarray data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), then, these data were annotated and analyzed to find dysregulated lncRNAs in RCC...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152102/l1-cell-adhesion-molecule-l1cam-is-a-strong-predictor-for-locoregional-recurrences-in-cervical-cancer
#17
Marlies Schrevel, Willem E Corver, Margit E Vegter, Natalja T Ter Haar, Enno J Dreef, Jogchum J Beltman, Gemma Kenter, Tjalling Bosse, Cornelis D de Kroon, Ekaterina S Jordanova
Background: L1 cell adhesion molecule (L1CAM) has been shown to be a prognostic marker in various cancer types, and has been suggested to play a role in epithelial mesenchymal transition (EMT). Here, we determined the prognostic significance of L1CAM in cervical cancer and its association with vimentin expression on tumor cells, indicative of EMT. Methods: Formalin-fixed, paraffin-embedded primary tumor samples from 372 cervical cancer patients were collected for immunohistochemical analysis of L1CAM expression...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152081/identification-of-lung-adenocarcinoma-specific-dysregulated-genes-with-diagnostic-and-prognostic-value-across-27-tcga-cancer-types
#18
Jun Shang, Qian Song, Zuyi Yang, Dongyao Li, Wenjie Chen, Lei Luo, Yongkun Wang, Jingcheng Yang, Shikang Li
As the most common histologic subtype of lung cancer, lung adenocarcinoma (LUAD) contributes to a majority of cancer-related deaths worldwide annually. In order to find specific biomarkers of LUAD that are able to distinguish LUAD from other types of cancer so as to improve the early diagnostic and prognostic power in LUAD, we analyzed 10098 tumor tissue samples across 27 TCGA cancer types and identified 112 specific expressed genes in LUAD. Meantime, 8240 LUAD dysregulated genes in tumor and normal samples were identified...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152079/an-analysis-of-the-gene-interaction-networks-identifying-the-role-of-parp1-in-metastasis-of-non-small-cell-lung-cancer
#19
Kai Chen, Yajie Li, Hui Xu, Chunfeng Zhang, Zhiqiang Li, Wei Wang, Baofeng Wang
Background and Objective: Though there were many researches about the effects of cancer cells on non-small cell lung cancer (NSCLC) currently, it has been rarely reported completed oncogene and its mechanism in tumors by far. Here, we used biological methods with known oncogene of NSCLC to find new oncogene and explore its functionary mechanism in NSCLC. Methods: The study firstly built NSCLC genetic interaction network based on bioinformatics methods and then combined shortest path algorithm with significance test to confirmed core genes that were closely involved with given genes; real-time qPCR was conducted to detect expression levels between patients with NSCLC and normal people; additionally, detection of PARP1's role in migration and invasion was performed by trans-well assays and wound-healing...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151892/metrics-to-estimate-differential-co-expression-networks
#20
Elpidio-Emmanuel Gonzalez-Valbuena, Víctor Treviño
Background: Detecting the differences in gene expression data is important for understanding the underlying molecular mechanisms. Although the differentially expressed genes are a large component, differences in correlation are becoming an interesting approach to achieving deeper insights. However, diverse metrics have been used to detect differential correlation, making selection and use of a single metric difficult. In addition, available implementations are metric-specific, complicating their use in different contexts...
2017: BioData Mining
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