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. 2021 Jun 2;9:682619. doi: 10.3389/fcell.2021.682619

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Copyright © 2021 Marquardt, Pavlopoulou, Takan, Dhar, Pützer and Logotheti.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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JIGs are transcriptionally deregulated in invasive/metastatic stages and predict clinical outcomes in a cancer type-dependent manner. (A) JIG transcripts are deregulated in the highly invasive versus the less-invasive CCLE cell lines, and the total percentage is 1.8-fold higher than the corresponding percentage of control lists. Red: upregulated, blue: downregulated, pink: cancer type-dependent deregulation. Error bars represent mean with SD. (B) Red-boxed diagram: median expression correlation (MEC) in PanCan and SD of MEC (pink boxes) are higher among JIGs compared to random lists (shown are the 100 medians of MEC with maximal SD). Green-boxed diagram: the differences of positive versus negative area of correlation per gene show (a) a significantly larger span and (b) over all a higher positive value compared to 100 random gene lists. Pink lines represent the median, pink boxes represent SD. (C) Cox regression analysis of JIGs on the survival of the TCGA PanCan cohort. 227 JIGs correlated with patient outcomes, of which 141 predicted worse and 86 better outcomes. Among 159 deregulated JIGs in highly-aggressive states across several cancer types of CCLE, 118 JIGs (74.2%) influence patient prognosis. Of those, 74 (62.7%) (pie chart, blue) had an adverse effect, 51 were exclusively upregulated in aggressive states of CCLE (CCLE UP, plain red), while additional 10 JIGs were upregulated in some as well as downregulated in other cancer types (CCLE UP/DN, plain pink). Only 44 JIGs differentially expressed in CCLE (dashed blue, plain blue, and dashed pink) had a beneficial effect on survival prognosis (pie chart, green). (D) Transcriptional deregulation of JIGs in metastases versus primary tumor or normal tissue, and correlation with JIGs that affect patient prognosis in PanCan. JIG deregulations in 6 metastatic cancer types are more correlated with poor outcomes (1.85:1). (E) Survival analysis for JIGs across different TCGA cancers. The prognostic potential of JIGs depends on the cancer type. In the majority of cancer types, more JIGs are associated with poor prognosis and less with favorable prognosis. No cancer tissue was found unaffected by JIGs.