Survival Analysis of Multi-Omics Data Identifies Potential Prognostic Markers of Pancreatic Ductal Adenocarcinoma

In this study, we selected 153 PDAC patients from the TCGA database and used their clinical, DNA methylation, gene expression, and micro-RNA (miRNA) and long non-coding RNA (lncRNA) expression data for multi-omic analysis. Differential methylations at about 12,000 CpG sites were observed in PDAC tumor genomes, with about 61% of them hypermethylated, predominantly in the promoter regions and in CpG-islands. Chromosomes 20 and 18 showed the highest and lowest methylation densities, while chr7:27Mb-28Mb region turned out as the most hypermethylated region in the entire genome, which hosts several HOX-family genes. We correlated promoter methylation and gene expression for mRNAs and identified seventeen genes that were previously recognized as PDAC biomarkers. Our survival analysis identified 406 promoter methylation target loci associated with patients survival, including known esophageal squamous cell carcinoma biomarkers, cg03234186 (ZNF154), and cg02587316, cg18630667 and cg05020604 (ZNF382). Similarly, several genes (B3GNT3, DMBT1, DEPDC1B) and lncRNAs (PVT1, and GATA6-AS) are strongly correlated with survival, which have not been reported in PDAC before. Other genes such as EFR3B, whose biological roles are not well known in mammals are also found to strongly associated with survival. We further identified 406 promoter methylation target loci associated with patients survival, including known esophageal squamous cell carcinoma biomarkers, cg03234186 (ZNF154), and cg0258...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

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Abstract With the increasing awareness of heterogeneity in cancers, better prediction of cancer prognosis is much needed for more personalized treatment. Recently, extensive efforts have been made to explore the variations in gene expression for better prognosis. However, the prognostic gene signatures predicted by most existing methods have little robustness among different datasets of the same cancer. To improve the robustness of the gene signatures, we propose a novel high-frequency sub-pathways mining approach (HiFreSP), integrating a randomization strategy with gene interaction pathways. We identified a six-g...
Source: Briefings in Bioinformatics - Category: Bioinformatics Authors: Tags: Brief Bioinform Source Type: research
This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: In OSCC, very low preoperative NLR values have a negative prognostic impact on survival and recurrence, similarly to high ratios. ENE and perineural spread are the most important clinical-pathologic prognosticators. Introduction Oral squamous cell carcinoma (OSCC) accounts for more than 95% of oral tumors and is the eighth most frequent cancer worldwide, with an estimated incidence of 640,000 new cases per year (1). Survival of OSCC has slightly improved over the last 30 years, probably as a consequence of multimodal treatment spreading. However, intensified therapeutic regimens can result in signific...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Junhui Zhang1,2†, Lingfei Li1,2†, Qiong Zhang1,2, Xu Yang3, Can Zhang4, Xingyue Zhang1,2, Dongxia Zhang1,2, Yanling Lv1,2, Huapei Song1,2, Bing Chen5, Yao Liu6, Jiongyu Hu2,5*† and Yuesheng Huang1,2*† 1Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China 2State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China 3Department of Respiratory Medicine, The 983 Hospital of Joint Logistics Support Force of the Chinese Peopl...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Joe Abdo1, Christopher S. Wichman2, Nicholas E. Dietz1,3, Pawel Ciborowski4, John Fleegel1, Sumeet K. Mittal1,5 and Devendra K. Agrawal1* 1Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States 2Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States 3Department of Pathology, CHI Health Creighton University Medical Center, College of Medicine, Omaha, NE, United States 4Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE, United States 5Norton Thoracic Institute, St....
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Yi He†, Wenyong Long† and Qing Liu* Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China Super-enhancers (SEs) refer to large clusters of enhancers that drive gene expressions. Recent data has provided novel insights in elucidating the roles of SEs in many diseases, including cancer. Many mechanisms involved in tumorigenesis and progression, ranging from internal gene mutation and rearrangement to external damage and inducement, have been demonstrated to be highly associated with SEs. Moreover, translocation, formation, deletion, or duplication of SEs themselves co...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Federico Altieri1, Tommy V. Hansen2 and Fabio Vandin1* 1Department of Information Engineering, University of Padova, Padova, Italy 2Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark Next-generation sequencing technologies allow to measure somatic mutations in a large number of patients from the same cancer type: one of the main goals in their analysis is the identification of mutations associated with clinical parameters. The identification of such relationships is hindered by extensive genetic heterogeneity in tumors, with different genes mutated in different patien...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
In conclusion, this study demonstrates that WG-391D exhibits strong antitumor activity against ovarian cancer and indicates that the down-regulation of CDC25B by inhibitors could provide a rationale for ovarian cancer therapy. Introduction Ovarian cancer is one of the most common malignances in females. The American Cancer Society estimated that there were 22,240 cases of ovarian cancer, and 14,070 deaths, in the United States in 2018 (1). During its early stages, ovarian cancer can be asymptomatic; hence, ~70% of patients have advanced disease when diagnosed and ultimately develop chemotherapeutic drug resistance an...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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