Identification of key genes in lung adenocarcinoma based on a competing endogenous RNA network

Song, Zikun; Zhang, Yinjiang; Chen, Zheren; Zhang, Bicheng

doi:10.3892/ol.2020.12322

Cited by 12 publications

(7 citation statements)

References 46 publications

(49 reference statements)

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“…Interestingly, a long noncoding RNA was found to be encoded on the antisense strand of RAMP2 and was denoted RAMP2-AS1. RAMP2-AS1 regulates endothelial cell homeostasis and may also play a role in cancer-related angiogenesis ( Cheng et al, 2020 ; Hassani et al, 2021 ; Lai et al, 2021 ; Song et al, 2021 ; Li et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

et al. 2022

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G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent of these interactions and the mechanisms of their effects are not well understood. For example, one class of GPCR-interacting proteins, receptor activity-modifying proteins (RAMPs), comprise three related and ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, and since then GPCR–RAMP interactions and their functional consequences on receptor trafficking and ligand selectivity have been documented for several secretin (class B) GPCRs, most notably the calcitonin receptor-like receptor. Recent bioinformatics and multiplexed experimental studies suggest that GPCR–RAMP interactions might be much more widespread than previously anticipated. Recently, cryo-electron microscopy has provided high-resolution structures of GPCR–RAMP–ligand complexes, and drugs have been developed that target GPCR–RAMP complexes. In this review, we provide a summary of recent advances in techniques that allow the discovery of GPCR–RAMP interactions and their functional consequences and highlight prospects for future advances. We also provide an up-to-date list of reported GPCR–RAMP interactions based on a review of the current literature. Significance Statement Receptor activity-modifying proteins (RAMPs) have emerged as modulators of many aspects of G protein-coupled receptor (GPCR)biology and pharmacology. The application of new methodologies to study membrane protein–protein interactions suggests that RAMPs interact with many more GPCRs than had been previously known. These findings, especially when combined with structural studies of membrane protein complexes, have significant implications for advancing GPCR-targeted drug discovery and the understanding of GPCR pharmacology, biology, and regulation.

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Section: Introductionmentioning

confidence: 99%

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

et al. 2022

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“…The AUCs of their established prognostic model for predicting patients' survival at 1, 3, and 5 years were 0.692, 0.722, and 0.651 in the test data, respectively. Song et al 16 reported fifty genes that may be associated with CD44, CCND3, NCALD, and MACF1 and suggested that miR-296-5p, RAMP2-AS1, CD44, CCND3, NCALD, and MACF1 may serve as potential reliable biomarkers for the detection of LUAD.…”

Section: Introductionmentioning

confidence: 99%

Functional Effects of Four or Fewer Critical Genes Linked to Lung Cancers and New Subtypes Detected by A New Machine Learning Classifier

Zhang¹

2021

Preprint

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Finding genes biologically directly or indirectly related to lung cancer has been drawing much attention, and many genes directly related to lung cancer have been reported. However, it has not been confirmed whether those published 'key' genes are truly critical to lung cancer formation, i.e., they may be with very limited useful information. As a result, finding essential genes remains a challenging lung cancer research problem. Using a recently developed competing linear factor analysis method in differentially expressed gene detection, we advance the study of lung cancer critical genes detection to a uniformly informative level. A set of common four genes and their functional effects are detected to be differentially expressed in tumor and non-tumor samples with 100% sensitivity and 100% specificity in one study of lung adenocarcinoma (LUAD) and one study of squamous cell lung cancers (LUSC) (two North American cohorts with 20429 genes, 576 and 552 samples respectively). Two additional analyses also gain accuracy of 97.8% sensitivity and 100% specificity in one study of non-small cell lung carcinomas (NSCLC, a European cohort with 20356 genes and 156 samples), and an accuracy of 100% sensitivity and 95% specificity (1 out of 20 non-tumor samples) in one study of ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas (LUAD, a Japanese cohort with 20356 genes and 224 samples). There are some common genes, but different functional effects, within each set of four genes among two North American cohorts and a European cohort and among North American cohorts and the Japanese cohort. These results show the four-gene-based classifiers are robust with different types of lung cancers and different race cohorts and accurate. The functional effects of four genes disclose significantly other mechanisms (mysteries) between LUAD and LUSC. These sets of four genes and their functional effects are considered to be essential for lung cancer studies and practice. These genes' functional effects naturally classify patients into different groups (more than seven subtypes). Subtype information is useful for personalized therapies. The new findings can motivate new lung cancer research in more focused and targeted directions to save lives, protect people, and reduce enormous economic costs in research and lung cancer treatments.

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“…In LUAD, “high” expressing groups of both COL7A1 and NTSR1 demonstrated reduced NCALD, the gene whose low expression worsens patient outcome 89 . Furthermore, CCND3, whose high expression improves survival 79 , was reduced in the COL7A1 high group while CD44 , a promoter of KRAS-dependent lung tumorigenesis 90 , was elevated in the NTSR1 high group. Lastly, KRT1 high BLCA patients had significantly higher expression of EGFR and MKI67 , suggesting that proliferation is potentiated in this group; this complements the survival analysis (high KRT1 is unfavorable in BLCA) and IHC data ( KRT1 staining is higher in cancer than normal specimens).…”

Section: Discussionmentioning

confidence: 94%

“…All genes with satisfactory AUC were subjected to analysis of IHC data. Their influence on tumor progression was also evaluated; each cancer was considered separately, with progression-related genes being selected for BLCA 77 , ESCA 78 , LUAD 79 , PAAD 80 , 81 and UCEC 82 based on literature. The prognostic value of EMX2 suggests it as a favorable marker for DFS and the staining confirms that it is present at a higher level in normal endometrial tissue than in tumor, as noted previously 83 .…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of AP-2α/γ targets as cancer therapeutics

Kołat

Kałuzińska

Płuciennik

2022

Sci Rep

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Identifying genes with prognostic importance could improve cancer treatment. An increasing number of reports suggest the existence of successful strategies based on seemingly “untargetable” transcription factors. In addition to embryogenesis, AP-2 transcription factors are known to play crucial roles in cancer development. Members of this family can be used as prognostic factors in oncological patients, and AP-2α/γ transcription factors were previously investigated in our pan-cancer comparative study using their target genes. The present study investigates tumors that were previously found similar with an emphasis on the possible role of AP-2 factors in specific cancer types. The RData workspace was loaded back to R environment and 3D trajectories were built via Monocle3. The genes that met the requirement of specificity were listed using top_markers(), separately for mutual and unique targets. Furthermore, the candidate genes had to meet the following requirements: correlation with AP-2 factor (through Correlation AnalyzeR) and validated prognostic importance (using GEPIA2 and subsequently KM-plotter or LOGpc). Eventually, the ROC analysis was applied to confirm their predictive value; co-dependence of expression was visualized via BoxPlotR. Some similar tumors were differentiated by AP-2α/γ targets with prognostic value. Requirements were met by only fifteen genes (EMX2, COL7A1, GRIA1, KRT1, KRT14, SLC12A5, SEZ6L, PTPRN, SCG5, DPP6, NTSR1, ARX, COL4A3, PPEF1 and TMEM59L); of these, the last four were excluded based on ROC curves. All the above genes were confronted with the literature, with an emphasis on the possible role played by AP-2 factors in specific cancers. Following ROC analysis, the genes were verified using immunohistochemistry data and progression-related signatures. Staining differences were observed, as well as co-dependence on the expression of e.g. CTNNB1, ERBB2, KRAS, SMAD4, EGFR or MKI67. In conclusion, prognostic value of targets suggested AP-2α/γ as candidates for novel cancer treatment. It was also revealed that AP-2 targets are related to tumor progression and that some mutual target genes could be inversely regulated.

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Identification of key genes in lung adenocarcinoma based on a competing endogenous RNA network

Cited by 12 publications

References 46 publications

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

Functional Effects of Four or Fewer Critical Genes Linked to Lung Cancers and New Subtypes Detected by A New Machine Learning Classifier

Prognostic significance of AP-2α/γ targets as cancer therapeutics

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