Constructing cancer patient-specific and group-specific gene networks with multi-omics data.

Published on Aug 27, 2020in BMC Medical Genomics3.063
· DOI :10.1186/S12920-020-00736-7
Wook Lee6
Estimated H-index: 6
(Inha University),
De-Shuang Huang63
Estimated H-index: 63
(Tongji University),
Kyungsook Han26
Estimated H-index: 26
(Inha University)
Cancer is a complex and heterogeneous disease with many possible genetic and environmental causes. The same treatment for patients of the same cancer type often results in different outcomes in terms of efficacy and side effects of the treatment. Thus, the molecular characterization of individual cancer patients is increasingly important to find an effective treatment. Recently a few methods have been developed to construct cancer sample-specific gene networks based on the difference in the mRNA expression levels between the cancer sample and reference samples. We constructed a patient-specific network with multi-omics data based on the difference between a reference network and a perturbed reference network by the patient. A network specific to a group of patients was obtained using the average change in correlation coefficients and node degree of patient-specific networks of the group. In this paper, we present a new method for constructing cancer patient-specific and group-specific gene networks with multi-omics data. The main differences of our method from previous ones are as follows: (1) networks are constructed with multi-omics (mRNA expression, copy number variation, DNA methylation and microRNA expression) data rather than with mRNA expression data alone, (2) background networks are constructed with both normal samples and cancer samples of the specified type to extract cancer-specific gene correlations, and (3) both patient individual-specific networks and patient group-specific networks can be constructed. The results of evaluating our method with several types of cancer show that it constructs more informative and accurate gene networks than previous methods. The results of evaluating our method with extensive data of seven cancer types show that the difference of gene correlations between the reference samples and a patient sample is a more predictive feature than mRNA expression levels and that gene networks constructed with multi-omics data show a better performance than those with single omics data in predicting cancer for most cancer types. Our approach will be useful for finding genes and gene pairs to tailor treatments to individual characteristics.
#2Chi-Chun Wong (CUHK: The Chinese University of Hong Kong)H-Index: 3
Background The incidence of colorectal cancer (CRC) is rapidly rising worldwide. Understanding the molecular mechanism underlying CRC pathogenesis is critical to uncover novel drug targets and diagnostics for this disease. Our preliminary work identified SCNN1B as an outlier down-regulated in CRC. SCNN1B mRNA and protein expression were down-regulated in primary CRC and CRC cell lines, suggesting that it might function as a tumor suppressor in CRC. Methods Clinical significance of SCNN1B in eval...
#1Jiao Luo (SC: University of Southern California)H-Index: 5
#2Nyam-Osor Chimge (SC: University of Southern California)H-Index: 7
Last. Zea BorokH-Index: 63
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: Claudins are a family of transmembrane proteins integral to the structure and function of tight junctions (TJ). Disruption of TJ and alterations in claudin expression are important features of invasive and metastatic cancer cells. Expression of CLDN18.1, the lung-specific isoform of CLDN18, is markedly decreased in lung adenocarcinoma (LuAd). Furthermore, we recently observed that aged Cldn18 -/- mice have increased propensity to develop LuAd. We now demonstrate that CLDN18.1 expression correl...
#1Justin W. Mabin (OSU: Ohio State University)H-Index: 4
#2Lauren A. Woodward (OSU: Ohio State University)H-Index: 4
Last. Guramrit Singh (OSU: Ohio State University)H-Index: 17
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Summary The exon junction complex (EJC) deposited upstream of mRNA exon junctions shapes structure, composition, and fate of spliced mRNA ribonucleoprotein particles (mRNPs). To achieve this, the EJC core nucleates assembly of a dynamic shell of peripheral proteins that function in diverse post-transcriptional processes. To illuminate consequences of EJC composition change, we purified EJCs from human cells via peripheral proteins RNPS1 and CASC3. We show that the EJC originates as an SR-rich me...
#1Hongyang Li (UM: University of Michigan)H-Index: 3
#2Tingyang Li (UM: University of Michigan)H-Index: 2
Last. Yuanfang Guan (UM: University of Michigan)H-Index: 32
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Combination therapies are commonly used to treat patients with complex diseases that respond poorly to single-agent therapies. In vitro high-throughput drug screening is a standard method for pre-clinical prioritization of synergistic drug combinations, but it can be impractical for large drug sets. Computational methods are thus being actively explored; however, most published methods were built on a limited size of cancer cell lines or drugs, and it remains a challenge to predict synergism at ...
#1Yuan Li (Peking Union Medical College)H-Index: 21
#2Jiagen Li (Peking Union Medical College)H-Index: 14
Last. Jie He (Peking Union Medical College)H-Index: 59
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Abstract Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Here, we identified a novel NSUN2 methylated lncRNA (NMR), which was significantly upregulated in esophageal squamous cell carcinoma (ESCC), functioned as a key regulator of ESCC tumor metastasis and drug resistance. Upregulation of NMR correlated with tumor metastasis and indicated poor overall survival in ESCC patients. Functionally, NMR could promote tumor cell migration and invasio...
#1Valsamma Abraham (UPenn: University of Pennsylvania)H-Index: 8
#2G. Cao (RU: Rutgers University)H-Index: 9
Last. Horace M. DeLisser (UPenn: University of Pennsylvania)H-Index: 37
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: Platelet endothelial cell adhesion molecule‑1 (PECAM‑1) is expressed on the vascular endothelium and has been implicated in the late progression of metastatic tumors. The activity of PECAM‑1 appears to be mediated by modulation of the tumor microenvironment (TME) and promotion of tumor cell proliferation, rather than through the stimulation of tumor angiogenesis. The present study aimed to extend those initial findings by indicating that the presence of functional PECAM‑1 on the endothelium pr...
#1Wei Zhang (UCSD: University of California, San Diego)H-Index: 20
#2Jianzhu Ma (UCSD: University of California, San Diego)H-Index: 22
Last. Trey Ideker (UCSD: University of California, San Diego)H-Index: 98
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Motivation: Network propagation has been widely used to aggregate and amplify the effects of tumor mutations using knowledge of molecular interaction networks. However, propagating mutations through interactions irrelevant to cancer leads to erosion of pathway signals and complicates the identification of cancer subtypes. Results: To address this problem we introduce a propagation algorithm, Network-Based Supervised Stratification (NBS2), which learns the mutated subnetworks underlying tumor sub...
#1Lingeng Lu (Yale Cancer Center)H-Index: 48
#2Gongjian ZhuH-Index: 7
Last. Klaus Holzmann (Medical University of Vienna)H-Index: 31
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ABSTRACTNSUN2 is a tRNA methyltransferase and plays an important role in cell development via modifying RNA methylation. We aimed to evaluate the expression of NSUN2 and its prognostic value in HNSCC. Random-effects model of meta-analysis shows 1.99-folds (95% CI: 1.89–2.09) upregulation of NSUN2 expression in HNSCC versus normal tissues. Patients with high NSUN2 levels had approximately 22 months shorter overall survival, and had a higher mortality risk than those with low one (p-trend = 0.020)...
#1Siwei Liu (Academy of Medical Sciences, United Kingdom)H-Index: 4
#2Huajiang Lei (Academy of Medical Sciences, United Kingdom)H-Index: 3
Last. Lan Xie (Academy of Medical Sciences, United Kingdom)H-Index: 3
view all 5 authors...
: This study aimed at investigating the biological functions of long non-coding RNAs (lncRNAs) hox transcript antisense intergenic RNA (HOTAIR) in resistant ovarian cancer cells, exploring the regulation effect of HOTAIR on HOXA7, and investigating their influence on the chemosensitivity of ovarian cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for the verification of HOTAIR expression in resistant and sensitive groups. How HOTAIR downregulation affected cel...
#1Jieting Tang (CUHK: The Chinese University of Hong Kong)H-Index: 1
#2Huarong Chen (CUHK: The Chinese University of Hong Kong)H-Index: 16
Last. Jun Yu (CUHK: The Chinese University of Hong Kong)H-Index: 138
view all 10 authors...
Copy number alterations (CNAs) are crucial for colorectal cancer (CRC) development. In this study, DEAD box polypeptide 27 (DDX27) was identified to be highly amplified in both TCGA CRC (474/615) and primary CRC (47/103), which was positively correlated with its mRNA overexpression. High DDX27 mRNA (N = 199) and protein expression (N = 260) predicted poor survival in CRC patients. Ectopic expression of DDX27 increased CRC cells proliferation, migration and invasion, but suppressed apoptosis. Con...
Cited By2
#2Junkai ZhuH-Index: 2
Last. Fangrong YanH-Index: 14
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Tumour immunotherapy combined with molecular typing is a new therapy to help select patients. However, molecular typing algorithms related to tumour immune function have not been thoroughly explored. We herein proposed a single sample immune signature network (SING) method to identify new immune function-related subtypes of cutaneous melanoma of the skin. A sample-specific network and tumour microenvironment were constructed based on the immune annotation of cutaneous melanoma samples. Then, the...
#1Anna Malczewska (Medical University of Silesia)H-Index: 13
#2Kjell Öberg (Uppsala University Hospital)H-Index: 117
Last. Beata Kos-Kudła (Medical University of Silesia)H-Index: 31
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Introduction The absence of a reliable, universal biomarker is a significant limitation in neuroendocrine neoplasia (NEN) management. We prospectively evaluated two CgA assays, (NEOLISA, EuroDiagnostica) and (CgA ELISA, Demeditec Diagnostics (DD)) and compared the results to the NETest. Methods NEN cohort (n = 258): pancreatic, n = 67; small intestine, n = 40; appendiceal, n = 10; rectal, n = 45; duodenal, n = 9; gastric, n = 44; lung, n = 43. Image-positive disease (IPD) (n = 123), image & hist...
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