Dataset Information

Long noncoding RNA MIR31HG is a bona fide prognostic marker with colorectal cancer cell-intrinsic properties.

ABSTRACT: Elevated miR-31 expression is associated with poor outcome in colorectal cancer (CRC). Whether the prognostic information is independent of known molecular subgroups and gene expression-based consensus molecular subtypes (CMS) is currently unknown. To investigate this, we analyzed nearly 2000 CRC biopsies and preclinical models. The expression of miR-31-5p and its host transcript, long noncoding RNA MIR31HG, was strongly correlated (Spearman's ? > 0.80). MIR31HG outlier expression was observed in 158/1265 (12%) of pCRCs and was associated with depletion of CMS2-canonical subgroup (odds ratio = 0.21 [0.11-0.35]) and shorter relapse-free survival (RFS) in multivariable analysis (adjusted hazard ratio = 2.2 [1.6-3.0]). For stage II disease, 5-year RFS for patients with MIR31HG outlier status was 49% compared to 77% for those with normal-like expression. MIR31HG outlier status was associated with inferior outcome also within clinical high risk groups and within the poor prognostic CMS4-mesenchymal gene expression subtype specifically. Preclinical models with MIR31HG outlier expression were characterized by reduced expression of MYC targets as well as elevated epithelial-mesenchymal transition, TNF-?/NF?B, TGF-?, and IFN-?/? gene expression signatures, indicating cancer cell-intrinsic properties resembling the CMS4 subgroup-associations which were recapitulated in patient biopsies. Moreover, the prognostic value of MIR31HG outlier status was independent of cytotoxic T lymphocyte and fibroblast infiltration. We here present evidence that MIR31HG expression provides clinical stratification beyond major gene expression phenotypes and tumor immune and stromal cell infiltration and propose a model where increased expression is an indicator of a cellular state conferring intrinsic invasive and/or immuno-evasive capabilities.

SUBMITTER: Eide PW

PROVIDER: S-EPMC6590447 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long noncoding RNA MIR31HG is a bona fide prognostic marker with colorectal cancer cell-intrinsic properties.

Eide Peter W PW Eilertsen Ina A IA Sveen Anita A Lothe Ragnhild A RA

International journal of cancer 20190112 11

Elevated miR-31 expression is associated with poor outcome in colorectal cancer (CRC). Whether the prognostic information is independent of known molecular subgroups and gene expression-based consensus molecular subtypes (CMS) is currently unknown. To investigate this, we analyzed nearly 2000 CRC biopsies and preclinical models. The expression of miR-31-5p and its host transcript, long noncoding RNA MIR31HG, was strongly correlated (Spearman's ρ > 0.80). MIR31HG outlier expression was observed i ...[more]

PMID: 30447009

Similar Datasets

Project description:UnlabelledMammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions.ImportancePrions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative disorders. Other aggregation-prone proteins appear to have a prion-like mode of expansion in brains, such as in Alzheimer's or Parkinson's diseases. To date, the resolution of prion structure remains elusive. Thus, to genetically define the landscape of regions critical for prion conversion, we tested the effect of short deletions. We found that, surprisingly, removal of a portion of PrP, the C terminus of alpha-helix H2, did not hamper prion formation but generated infectious agents with an internal deletion that showed characteristics essentially similar to those of original infecting strains. Thus, we demonstrate that completeness of the residues inside prions is not necessary for maintaining infectivity and the main strain-specific information, while reporting one of the few if not the only bona fide prions with an internal deletion.

Project description:Objective: Pupil dilation patterns are outside of conscious control and provide information regarding neuropsychological processes related to deception, cognitive effort, and familiarity. This study examined the incremental utility of pupillometry on the Test of Memory Malingering (TOMM) in classifying individuals with verified traumatic brain injury (TBI), individuals simulating TBI, and healthy comparisons. Method: Participants were 177 adults across three groups: verified TBI (n = 53), feigned cognitive impairment due to TBI (SIM, n = 52), and heathy comparisons (HC, n = 72). Results: Logistic regression and ROC curve analyses identified several pupil indices that discriminated the groups. Pupillometry discriminated best for the comparison of greatest clinical interest, verified TBI versus simulators, adding information beyond traditional accuracy scores. Simulators showed evidence of greater cognitive load than both groups instructed to perform at their best ability (HC and TBI). Additionally, the typically robust phenomenon of dilating to familiar stimuli was relatively diminished among TBI simulators compared to TBI and HC. This finding may reflect competing, interfering effects of cognitive effort that are frequently observed in pupillary reactivity during deception. However, the familiarity effect appeared on nearly half the trials for SIM participants. Among those trials evidencing the familiarity response, selection of the unfamiliar stimulus (i.e., dilation-response inconsistency) was associated with a sizeable increase in likelihood of being a simulator. Conclusions: Taken together, these findings provide strong support for multimethod assessment: adding unique performance assessments such as biometrics to standard accuracy scores. Continued study of pupillometry will enhance the identification of simulators who are not detected by traditional performance validity test scoring metrics. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dataset Information

Long noncoding RNA MIR31HG is a bona fide prognostic marker with colorectal cancer cell-intrinsic properties.

Publications

Long noncoding RNA MIR31HG is a bona fide prognostic marker with colorectal cancer cell-intrinsic properties.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets