Dataset Information

Integrative proteo-transcriptomic and immunophenotyping signatures of HIV-1 elite control phenotype: A cross-talk between glycolysis and HIF signaling.

ABSTRACT: Natural control of HIV-1 is a characteristic of <1% of HIV-1-infected individuals, so called elite controllers (EC). In this study, we sought to identify signaling pathways associated with the EC phenotype using integrative proteo-transcriptomic analysis and immunophenotyping. We found HIF signaling and glycolysis as specific traits of the EC phenotype together with dysregulation of HIF target gene transcription. A higher proportion of HIF-1α and HIF-1β in the nuclei of CD4⁺ and CD8⁺ T cells in the male EC were observed, indicating a potential increased activation of the HIF signaling pathway. Furthermore, intracellular glucose levels were elevated in EC even as the surface expression of the metabolite transporters Glut1 and MCT-1 were decreased on lymphocytes indicative of unique metabolic uptake and flux profile. Combined, our data show that glycolytic modulation and altered HIF signaling is a unique feature of the male EC phenotype that may contribute to natural control of HIV-1.

SUBMITTER: Akusjarvi SS

PROVIDER: S-EPMC8718889 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Integrative proteo-transcriptomic and immunophenotyping signatures of HIV-1 elite control phenotype: A cross-talk between glycolysis and HIF signaling.

Akusjärvi Sara Svensson SS Ambikan Anoop T AT Krishnan Shuba S Gupta Soham S Sperk Maike M Végvári Ákos Á Mikaeloff Flora F Healy Katie K Vesterbacka Jan J Nowak Piotr P Sönnerborg Anders A Neogi Ujjwal U

iScience 20211210 1

Natural control of HIV-1 is a characteristic of <1% of HIV-1-infected individuals, so called elite controllers (EC). In this study, we sought to identify signaling pathways associated with the EC phenotype using integrative proteo-transcriptomic analysis and immunophenotyping. We found HIF signaling and glycolysis as specific traits of the EC phenotype together with dysregulation of HIF target gene transcription. A higher proportion of HIF-1α and HIF-1β in the nuclei of CD4<sup>+</sup> and CD8<s ...[more]

PMID: 35005552

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Project description:BackgroundThe survival prognosis is the hallmark of cancer progression. Here, we aimed to develop a recurrence-related gene signature to predict the prognosis of colon adenocarcinoma (COAD).MethodsThe proteomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and genomic data from the cancer genomic maps [The Cancer Genome Atlas (TCGA)] dataset were analyzed to identify co-differentially expressed genes (cDEGs) between recurrence samples and non-recurrence samples in COAD using limma package. Functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was conducted. Univariate and multivariate Cox regressions were applied to identify the independent prognostic feature cDEGs and establish the signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell's concordance index (C-index), and calibration curve. The area under the receiver operating characteristic (ROC) curve (AUROC) and a nomogram were calculated to assess the predictive accuracy. GSE17538 and GSE39582 were used for external validation. Quantitative real-time PCR and Western blot analysis were carried out to validate our findings.ResultsWe identified 86 cDEGs in recurrence samples compared with non-recurrence samples. These genes were primarily enriched in the regulation of carbon metabolic process, fructose and mannose metabolism, and extracellular exosome. Then, an eight-gene-based signature (CA12, HBB, NCF1, KBTBD11, MMAA, DMBT1, AHNAK2, and FBLN2) was developed to separate patients into high- and low-risk groups. Patients in the low-risk group had significantly better prognosis than those in the high-risk group. Four prognostic clinical features, including pathological M, N, T, and RS model status, were screened for building the nomogram survival model. The PCR and Western blot analysis results suggested that CA12 and AHNAK2 were significantly upregulated, while MMAA and DMBT1 were downregulated in the tumor sample compared with adjacent tissues, and in non-recurrent samples compared with non-recurrent samples in COAD.ConclusionThese identified recurrence-related gene signatures might provide an effective prognostic predictor and promising therapeutic targets for COAD patients.

Dataset Information

Integrative proteo-transcriptomic and immunophenotyping signatures of HIV-1 elite control phenotype: A cross-talk between glycolysis and HIF signaling.

Publications

Integrative proteo-transcriptomic and immunophenotyping signatures of HIV-1 elite control phenotype: A cross-talk between glycolysis and HIF signaling.

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