Robust method for identification of prognostic gene signatures from gene expression profiles

Sim, Woogwang; Lee, Jungsul; Choi, Chulhee

doi:10.1038/s41598-017-17213-4

Cited by 8 publications

(9 citation statements)

References 46 publications

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“…The integrin receptor family consists of 18 α subunits and 8 β subunits that assemble as non-covalently connected heterodimers and organized into 24 different ITGs 7 . Our current in silico study and another previous report suggest that ITGα3 plays a significant role in adverse prognosis of pancreatic cancer 8,9 . However, the underlying mechanism is poorly understood.…”

Section: Introductionsupporting

confidence: 69%

Blockade of integrin α3 attenuates human pancreatic cancer via inhibition of EGFR signalling

Lee

Choi

Kim

2019

Sci Rep

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The prognosis of pancreatic cancer remains dismal despite continuous and considerable efforts. Integrins (ITGs) are highly expressed in various malignant cancers. However, very few studies investigated the role of integrin α3 (ITGα3 ) in malignant cancers. Here, we determined the functional role of ITGα3 in pancreatic cancer. Analysis of public microarray databases and Western blot analysis indicated a unique expression of ITGα3 in human pancreatic cancer. Silencing ITGα3 expression significantly inhibited the viability and migration of human pancreatic cancer cells. Notably, ablation of ITGα3 expression resulted in a significant decrease of epidermal growth factor receptor (EGFR) expression compared with transfection of control-siRNA through an increased number of leucine-rich repeats and immunoglobulin-like domain protein 1 (LRIG1) expression. In addition, ablating ITGα3 inhibited tumour growth via blockade of EGFR signalling in vivo . Furthermore, the highly expressed ITGα3 led to a poor prognosis of pancreatic cancer patients. Our results provide novel insights into ITGα3-induced aggressive pancreatic cancer.

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Section: Introductionsupporting

confidence: 69%

Blockade of integrin α3 attenuates human pancreatic cancer via inhibition of EGFR signalling

Lee

Choi

Kim

2019

Sci Rep

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“…Researchers recently reported two prognostic gene signatures constructed using DCBLD2 in PDAC ( Raman et al, 2018 ; Feng et al, 2020 ). The prognostic accuracy of DCBLD2 was certainly inferior to that of gene models, because accumulating evidence had demonstrated that multi-gene signatures achieved higher prognostic accuracy compared with a single gene ( Beane et al, 2009 ; Sim et al, 2017 ; Schmidt et al, 2018 ; Huang et al, 2020 ; Ahluwalia et al, 2021 ). However, we found that the diagnostic accuracy of DCBLD2 was close to or no less than that of gene models.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Profiling Identifies DCBLD2 as a Diagnostic and Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma

Feng

et al. 2021

Front. Mol. Biosci.

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Background: Accumulating evidence shows that the elevated expression of DCBLD2 (discoidin, CUB and LCCL domain-containing protein 2) is associated with unfavorable prognosis of various cancers. However, the correlation of DCBLD2 expression value with the diagnosis and prognosis of pancreatic ductal adenocarcinoma (PDAC) has not yet been elucidated. Methods: Univariate Cox regression analysis was used to screen robust survival-related genes. Expression pattern of selected genes was investigated in PDAC tissues and normal tissues from multiple cohorts. Kaplan–Meier (K–M) survival curves, ROC curves and calibration curves were employed to assess prognostic performance. The relationship between DCBLD2 expression and immune cell infiltrates was conducted by CIBERSORT software. Biological processes and KEGG pathway enrichment analyses were adopted to clarify the potential function of DCBLD2 in PDAC. Results: Univariate analysis, K–M survival curves and calibration curves indicated that DCBLD2 was a robust prognostic factor for PDAC with cross-cohort compatibility. Upregulation of DCBLD2 was observed in dissected PDAC tissues as well as extracellular vesicles from both plasma and serum samples of PDAC patients. Both DCBLD2 expression in tissue and extracellular vesicles had significant diagnostic value. Besides, DCBLD2 expression was correlated with infiltrating level of CD8+ T cells and macrophage M2 cells. Functional enrichment revealed that DCBLD2 might be involved in cell motility, angiogenesis, and cancer-associated pathways. Conclusion: Our study systematically analyzed the potential diagnostic, prognostic and therapeutic value of DCBLD2 in PDAC. All the findings indicated that DCBLD2 might play a considerably oncogenic role in PDAC with diagnostic, prognostic and therapeutic potential. These preliminary results of bioinformatics analyses need to be further validated in more prospective studies.

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“…In addition to optimizing the parametric space and modeling assumptions for better results, tests could be employed to analyze the performance of the pipeline on a variety of gene sets to better inform the interpretation of differential expression of the gene set of interest (GTs). Robustness testing could be employed to investigate the quality of the results from independent datasets (Sim et al 2017), for example, from a cancer dataset not provided by TCGA but of the same type. Permutation testing could be employed across randomly sampled subsets of data to define DEGs across permutations.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, new methods are constantly being developed to address issues related to the quality of differential expression analysis and improve the identification of DEGs. Recent methods have been proposed to overcome the issue of threshold decisions (Sim et al 2017), and to employ the knowledge of a gene’s prior probability of DE to better predict that gene’s differential expression across diverse biological experiments (Crow et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Differential expression of glycosyltransferases identified through comprehensive pan-cancer analysis

Vora

Cauley

et al. 2021

Preprint

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Despite accumulating evidence supporting a role for glycosylation in cancer progression and prognosis, the complexity of the human glycome and glycoproteome poses many challenges to understanding glycosylation-related events in cancer. In this study, a multifaceted genomics approach was applied to analyze the impact of differential expression of glycosyltransferases (GTs) in 16 cancers. An enzyme list was compiled and curated from numerous resources to create a consensus set of GTs. Resulting enzymes were analyzed for differential expression in cancer, and findings were integrated with experimental evidence from other analyses, including: similarity of healthy expression patterns across orthologous genes, miRNA expression, automatically-mined literature, curation of known cancer biomarkers, N-glycosylation impact, and survival analysis. The resulting list of GTs comprises 222 human enzymes based on annotations from five databases, 84 of which were differentially expressed in more than five cancers, and 14 of which were observed with the same direction of expression change across all implicated cancers. 25 high-value GT candidates were identified by cross-referencing multimodal analysis results, including PYGM, FUT6 and additional fucosyltransferases, several UDP-glucuronosyltransferases, and others, and are suggested for prioritization in future cancer biomarker studies. Relevant findings are available through OncoMX at https://data.oncomx.org, and the overarching pipeline can be used as a framework for similarly analysis across diverse evidence types in cancer. This work is expected to improve the understanding of glycosylation in cancer by transparently defining the space of glycosyltransferase enzymes and harmonizing variable experimental data to enable improved generation of data-driven cancer biomarker hypotheses.

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Robust method for identification of prognostic gene signatures from gene expression profiles

Cited by 8 publications

References 46 publications

Blockade of integrin α3 attenuates human pancreatic cancer via inhibition of EGFR signalling

Blockade of integrin α3 attenuates human pancreatic cancer via inhibition of EGFR signalling

Transcriptomic Profiling Identifies DCBLD2 as a Diagnostic and Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma

Differential expression of glycosyltransferases identified through comprehensive pan-cancer analysis

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