WGCNA identification of TLR7 as a novel diagnostic biomarker, progression and prognostic indicator, and immunotherapeutic target for stomach adenocarcinoma

Yuan, Qihang; Zhou, Qi; Ren, Jie; Wang, Guan; Yin, Chunlai; Shang, Dong; Xia, Shilin

doi:10.1002/cam4.3946

Cited by 22 publications

(19 citation statements)

References 34 publications

(35 reference statements)

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“…These genes were deemed as potential therapeutic targets for personalized treatment in tumor patients. Recently, along with the sequencing technology was rapidly developed, high-throughput genomics has been used for the exploration of tumor generation and progression-related genes ( 43 , 44 ). Moreover, the deep investigation of the molecular mechanisms of tumorigenesis and development can be implemented by high-throughput genomics.…”

Section: Discussionmentioning

confidence: 99%

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma

et al. 2022

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BackgroundDespite the comparatively low prevalence of osteosarcoma (OS) compared to other cancer types, metastatic OS has a poor overall survival rate of fewer than 30%. Accumulating data has shown the crucial functions of immunogenic cell death (ICD) in various cancers; nevertheless, the relationship between ICD and OS was not previously well understood. This research aims to determine the function of ICD in OS and construct an ICD-based prognostic panel.MethodsSingle cell RNA sequencing data from GSE162454 dataset distinguished malignant cells from normal cells in OS. The discrepancy in ICD scores and corresponding gene expression was intensively explored between malignant cells and normal cells. Using the RNA sequencing data of the TARGET-OS, GSE16091, GSE21257, and GSE39058 datasets, the molecular subtype of OS was determined by clustering seventeen ICD-related genes obtained from the literature. Differentially expressed genes (DEGs) between different molecular subtypes were identified to develop a novel ICD-associated prognostic panel.ResultsThe malignant cells had a remarkable decrease in the ICD scores and corresponding gene expression compared with normal cells. A total of 212 OS patients were successfully stratified into two subtypes: C1 and C2. C1-like OS patients were characterized by better prognostic outcomes, overexpression of ICD genes, activation of the ICD pathway, high inflitration abundance of immunocytes, and low expression levels of immune checkpoint genes (ICGs); however, the reverse is true in C2-like OS patients. Utilizing the limma programme in R, the DEGs between two subtypes were determined, and a 5-gene risk panel consisting of BAMBI, TMCC2, NOX4, DKK1, and CBS was developed through LASSO-Cox regression analysis. The internal- and external-verification cohorts were employed to verify the efficacy and precision of the risk panel. The AUC values of ROC curves indicated excellent prognostic prediction values of our risk panel.ConclusionsOverall, ICD represented a protective factor against OS, and our 5-gene risk panel serving as a biomarker could effectively evaluate the prognostic risk in patients with OS.

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Section: Discussionmentioning

confidence: 99%

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma

et al. 2022

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“…For instance, in 2021, Farhadian et al (2021) highlighted the pivotal role of GJA1, AP2A2, and NPAS3 in the lactation process using WGCNA algorithms. Our previous study also identified TLR7 as a candidate gene for stomach adenocarcinoma (STAD) via the WGCNA algorithm, and this could help predict the progression and prognosis of STAD and shed new light on its immunotherapy ( Yuan et al, 2021b ).…”

Section: Introductionmentioning

confidence: 99%

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms

et al. 2021

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Background: Pancreatic adenocarcinoma (PAAD) has a considerably bad prognosis, and its pathophysiologic mechanism remains unclear. Thus, we aimed to identify real hub genes to better explore the pathophysiology of PAAD and construct a prognostic panel to better predict the prognosis of PAAD using the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithms.Methods: WGCNA identified the modules most closely related to the PAAD stage and grade based on the Gene Expression Omnibus. The module genes significantly associated with PAAD progression and prognosis were considered as the real hub genes. Eligible genes in the most significant module were selected for construction and validation of a multigene prognostic signature based on the LASSO-Cox regression analysis in The Cancer Genome Atlas and the International Cancer Genome Consortium databases, respectively.Results: The brown module identified by WGCNA was most closely associated with the clinical characteristics of PAAD. Scaffold attachment factor B (SAFB) was significantly associated with PAAD progression and prognosis, and was identified as the real hub gene of PAAD. Moreover, both transcriptional and translational levels of SAFB were significantly lower in PAAD tissues compared with normal pancreatic tissues. In addition, a novel multigene-independent prognostic signature consisting of SAFB, SP1, and SERTAD3 was identified and verified. The predictive accuracy of our signature was superior to that of previous studies, especially for predicting 3- and 5-year survival probabilities. Furthermore, a prognostic nomogram based on independent prognostic variables was developed and validated using calibration curves. The predictive ability of this nomogram was also superior to the well-established AJCC stage and histological grade. The potential mechanisms of different prognoses between the high- and low-risk subgroups were also investigated using functional enrichment analysis, GSEA, ssGSEA, immune checkpoint analysis, and mutation profile analysis.Conclusion: SAFB was identified as the real hub gene of PAAD. A novel multigene-independent prognostic signature was successfully identified and validated to better predict PAAD prognosis. An accurate nomogram was also developed and verified to aid in the accurate treatment of tumors, as well as in early intervention.

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“…Categorical data were calculated by the Chi-square test or Fisher's exact test. In addition, the predicted probability of being diagnosed with HCC was used as a surrogate marker to construct the receiver operating characteristic (ROC) curve (Yuan et al, 2021b). And the area under the curve (AUC) was used as an accuracy index to evaluate the diagnostic performance of the miRNAs, miRNA panel, or AFP.…”

Section: Discussionmentioning

confidence: 99%

Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma

Yang

Dong

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Background: Diagnostic tools for hepatocellular carcinoma (HCC) are critical for patient treatment and prognosis. Thus, this study explored the diagnostic value of the exosomal microRNA panel for HCC.Methods: Expression profiles of microRNAs in exosomes and plasma of HCC and control groups were assessed using microRNA microarray analysis. Reverse transcription-quantitative PCR was applied to evaluate the expression of candidate microRNAs in blood samples from 50 HCC patients, 50 hepatic cirrhosis patients, and 50 healthy subjects. The area calculated the diagnostic accuracy of the microRNAs and microRNA panel under the receiver operating characteristic curve (AUC).Results: MicroRNA microarray analysis revealed that there were more differentially expressed microRNAs in the exosome HCC group than plasma HCC group. Among the 43 differentially expressed microRNAs contained in both exosomes and plasma, we finally decided to testify the expression and diagnostic significance of microRNA-26a, microRNA-29c, and microRNA-199a. The results indicated that expression of the microRNA-26a, microRNA-29c, and microRNA-199a in both exosomes and plasma was significantly lower in HCC patients compared with hepatic cirrhosis and healthy group. Interestingly, exosomal microRNAs were substantially more accurate in diagnosing HCC than microRNAs and alpha-fetoprotein in plasma. Moreover, the exosomal microRNA panel containing microRNA-26a, microRNA-29c, and microRNA-199a showed high accuracy in discriminating HCC from healthy (AUC = 0.994; sensitivity 100%; specificity 96%) and hepatic cirrhosis group (AUC = 0.965; sensitivity 92%; specificity 90%).Conclusion: This study revealed that the exosomal microRNA panel has high accuracy in diagnosing HCC and has important clinical significance.

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WGCNA identification of TLR7 as a novel diagnostic biomarker, progression and prognostic indicator, and immunotherapeutic target for stomach adenocarcinoma

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 22 publications

References 34 publications

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms

Exosomal microRNA panel as a diagnostic biomarker in patients with hepatocellular carcinoma

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