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Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq.

ABSTRACT: Tumor metastasis is a multistep process involving a number of genetic alterations so that the genetic diagnosis is got increasingly attentions today. The aim of this study was to use RNA-seq to screen the effective differential expression genes in the peripheral blood mononuclear cells for the hepatic carcinoma with metastasis. The results showed that hepatic carcinoma samples gathered according to different metastasis. CCL3, CCL3L1, JUN, IL8, and IL1B were identified in inflammation mediated by chemokine and cytokine signaling pathway (P00031) in the hepatic carcinoma samples with metastasis, and subsequently confirmed by quantitative real-time polymerase chain reaction. In conclusions, CCL3, CCL3L1, JUN, IL8, and IL1B have the potential to be considered as candidates for future molecular diagnosis of the hepatic carcinoma with metastasis. This work may provide us with new visions into the metastasis process and potential efficient clinical diagnosis in the future.

SUBMITTER: Shen Y

PROVIDER: S-EPMC5438623 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq.

Shen Yanting Y Bu Lu L Li Rui R Chen Zhenzhu Z Tian Fei F Lu Na N Ge Qinyu Q Bai Yunfei Y Lu Zuhong Z

Oncotarget 20170401 17

Tumor metastasis is a multistep process involving a number of genetic alterations so that the genetic diagnosis is got increasingly attentions today. The aim of this study was to use RNA-seq to screen the effective differential expression genes in the peripheral blood mononuclear cells for the hepatic carcinoma with metastasis. The results showed that hepatic carcinoma samples gathered according to different metastasis. CCL3, CCL3L1, JUN, IL8, and IL1B were identified in inflammation mediated by ...[more]

PMID: 28427195

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Project description:IntroductionIn sarcoidosis, peripheral lymphopenia and anergy have been associated with increased inflammation and maladaptive immune activity, likely promoting development of chronic and progressive disease. However, the molecular mechanisms that lead to reduced lymphocyte proportions, particularly CD4+ T-cells, have not been fully elucidated. We posit that paradoxical peripheral lymphopenia is characterized by a dysregulated transcriptomic network associated with cell function and fate that results from altered transcription factor targeting activity.MethodsMessenger RNA-sequencing (mRNA-seq) was performed on peripheral blood mononuclear cells (PBMCs) from ACCESS study subjects with sarcoidosis and matched controls and findings validated on a sarcoidosis case-control cohort and a sarcoidosis case series. Preserved PBMC transcriptomic networks between case-control cohorts were assessed to establish cellular associations with gene modules and define regulatory targeting involved in sarcoidosis immune dysregulation utilizing weighted gene co-expression network analysis and differential transcription factor involvement analysis. Network centrality measures identified master transcriptional regulators of subnetworks related to cell proliferation and death. Predictive models of differential PBMC proportions constructed from ACCESS target gene expression corroborated the relationship between aberrant transcription factor regulatory activity and imputed and clinical PBMC populations in the validation cohorts.ResultsWe identified two unique and preserved gene modules significantly associated with sarcoidosis immune dysregulation. Strikingly, increased expression of a monocyte-driven, and not a lymphocyte-driven, gene module related to innate immunity and cell death was the best predictor of peripheral CD4+ T-cell proportions. Within the gene network of this monocyte-driven module, TLE3 and CBX8 were determined to be master regulators of the cell death subnetwork. A core gene signature of differentially over-expressed target genes of TLE3 and CBX8 involved in cellular communication and immune response regulation accurately predicted imputed and clinical monocyte expansion and CD4+ T-cell depletion.ConclusionsAltered transcriptional regulation associated with aberrant gene expression of a monocyte-driven transcriptional network likely influences lymphocyte function and survival. Although further investigation is warranted, this indicates that crosstalk between hyperactive monocytes and lymphocytes may instigate peripheral lymphopenia and underlie sarcoidosis immune dysregulation and pathogenesis. Future therapies selectively targeting master regulators, or their targets, may mitigate dysregulated immune processes in sarcoidosis and disease progression.

Dataset Information

Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq.

Publications

Screening effective differential expression genes for hepatic carcinoma with metastasis in the peripheral blood mononuclear cells by RNA-seq.

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