Upregulation of ADAM12 Is Associated With a Poor Survival and Immune Cell Infiltration in Colon Adenocarcinoma

Huang, Zijing; Lai, Hao; Liao, Jiankun; Cai, Jinghua; Li, Baojia; Meng, Ling-Hou; Wang, Wentao; Mo, Xianwei; Qin, Haiquan

doi:10.3389/fonc.2021.729230

Cited by 13 publications

(19 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Figure 4A , HSD17B8 is a good candidate for advanced tumor stages ( Luque-García et al, 2010 ), and COLCA2 is recognized as a colorectal cancer-associated gene ( Yin et al, 2022 ). In Figure 4B , overexpression of COL10A1 enhances the proliferation, migration, and invasion of CRC cells ( Huang et al, 2018 ); MMP11 expression affects the immune response in CRC ( Buttacavoli et al, 2021 ); ADAM12 may play vital roles in the recruitment of immune cells in CRC ( Huang et al, 2021 ); and COMP promotes CRC cell proliferation partially through the activation of the PI3K/Akt/mTOR/p70S6K pathway ( Liu et al, 2018 ). In Figure 4C , ALDH4A1 deficiency leads to the accumulation of proline, which sustains the proliferation and survival of CRC cells ( Alaqbi et al, 2022 ), and MT3 plays a pivotal role in tumor formation, progression, and drug resistance ( Si and Lang, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of functional gene modules by integrating multi-omics data and known molecular interactions

Chen

Han

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

Multi-omics data integration has emerged as a promising approach to identify patient subgroups. However, in terms of grouping genes (or gene products) into co-expression modules, data integration methods suffer from two main drawbacks. First, most existing methods only consider genes or samples measured in all different datasets. Second, known molecular interactions (e.g., transcriptional regulatory interactions, protein–protein interactions and biological pathways) cannot be utilized to assist in module detection. Herein, we present a novel data integration framework, Correlation-based Local Approximation of Membership (CLAM), which provides two methodological innovations to address these limitations: 1) constructing a trans-omics neighborhood matrix by integrating multi-omics datasets and known molecular interactions, and 2) using a local approximation procedure to define gene modules from the matrix. Applying Correlation-based Local Approximation of Membership to human colorectal cancer (CRC) and mouse B-cell differentiation multi-omics data obtained from The Cancer Genome Atlas (TCGA), Clinical Proteomics Tumor Analysis Consortium (CPTAC), Gene Expression Omnibus (GEO) and ProteomeXchange database, we demonstrated its superior ability to recover biologically relevant modules and gene ontology (GO) terms. Further investigation of the colorectal cancer modules revealed numerous transcription factors and KEGG pathways that played crucial roles in colorectal cancer progression. Module-based survival analysis constructed four survival-related networks in which pairwise gene correlations were significantly correlated with colorectal cancer patient survival. Overall, the series of evaluations demonstrated the great potential of Correlation-based Local Approximation of Membership for identifying modular biomarkers for complex diseases. We implemented Correlation-based Local Approximation of Membership as a user-friendly application available at https://github.com/free1234hm/CLAM.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of functional gene modules by integrating multi-omics data and known molecular interactions

Chen

Han

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…Previous studies have reported that upregulation of ADAM12 is associated with poor survival ( 29 , 30 ), whereas reduced expression of E-cadherin has been revealed to be associated with poor prognosis in patients with CRC ( 13 ). In the present study, upregulated ADAM12 expression was observed in the CRC and metastatic lymph node tissues compared with in normal mucosa and non-metastatic lymph node tissues.…”

Section: Discussionmentioning

confidence: 99%

“…ADAM12 is overexpressed in various types of human cancer, including breast, lung, stomach and liver cancer, and is associated with tumor progression and poor prognoses (18)(19)(20)(21)(22). ADAM12 overexpression has been shown to enhance proliferation, inhibit apoptosis, and to be significantly associated with metastases and poor survival in patients with CRC (28)(29)(30)(31). Furthermore,…”

Section: Introductionmentioning

confidence: 99%

A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition

Park

et al. 2023

Int J Oncol

View full text Add to dashboard Cite

A disintegrin and metalloprotease 12 (ADAM12) and epithelial-mesenchymal transition (EMT) are linked in the metastasis of various types of cancer. The present study aimed to assess the ability of ADAM12 to induce EMT and its potential as a therapeutic target for colorectal cancer (CRC). ADAM12 expression in CRC cell lines, CRC tissues and a mouse model of peritoneal metastasis was assessed. The effect of ADAM12 on CRC EMT and metastasis was investigated using ADAM12-pcDNA6-myc and ADAM12-pGFP-C-shLenti constructs. ADAM12 overexpression enhanced the proliferation, migration, invasion and EMT of CRC cells. The phosphorylation levels of factors associated with the PI3K/Akt pathway were also increased by ADAM12 overexpression. The knockdown of ADAM12 reversed these effects. ADAM12 expression and the loss of E-cadherin expression were significantly associated with poorer survival compared with other expression statuses of both proteins. In a mouse model of peritoneal metastasis, overexpression of ADAM12 induced increased tumor weight and peritoneal carcinomatosis index compared with that in the negative control group. Conversely, knockdown of ADAM12 reversed these effects. Furthermore, E-cadherin expression was significantly decreased by overexpression of ADAM12 compared with in the negative control group. By contrast, E-cadherin expression was increased by knockdown of ADAM12 compared with in the negative control group. ADAM12 overexpression contributed to CRC metastasis by regulating EMT. In addition, in the mouse model of peritoneal metastasis, ADAM12 knockdown exhibited strong anti-metastatic action. Consequently, ADAM12 may be considered a therapeutic target for CRC metastasis.

show abstract

“…TIMER2.0 ( http://timer.cistrome.org/ ) was used to analyze the expression of TMED2 in different cancers, as described previously [ 13 ]. A survival analysis of the LUAD patients in the TMED2-low and high expression groups was performed using Kaplan-Meier plotter ( http://kmplot.com/analysis/index.php?p=service&cancer=lung ), as described previously [ 14 ]. The pan-cancer assay was downloaded from The Cancer Genome Atlas (TCGA) database, as described previously [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

“…Gene set enrichment analysis (GSEA) (4.0.3) was used to analyze LUAD-related genes from TCGA, as described previously [ 16 ]. A target gene assay was performed to analyze the related genes for mutation and prognosis using a website ( https://www.mutarget.com/analysis?type=target ), as described previously [ 14 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

Transmembrane p24 trafficking protein 2 regulates inflammation through the TLR4/NF-κB signaling pathway in lung adenocarcinoma

et al. 2022

View full text Add to dashboard Cite

Background To investigate the role of transmembrane p24 trafficking protein 2 (TMED2) in lung adenocarcinoma (LUAD) and determine whether TMED2 knockdown could inhibit LUAD in vitro and in vivo. Methods TIMER2.0, Kaplan-Meier plotter, gene set enrichment analysis (GSEA), Target Gene, and pan-cancer systems were used to predict the potential function of TMED2. Western blotting and immunohistochemistry were performed to analyze TMED2 expression in different tissues or cell lines. The proliferation, development, and apoptosis of LUAD were observed using a lentivirus-mediated TMED2 knockdown. Bioinformatics and western blot analysis of TMED2 against inflammation via the TLR4/NF-κB signaling pathway were conducted. Results TMED2 expression in LUAD tumor tissues was higher than that in normal tissues and positively correlated with poor survival in lung cancer and negatively correlated with apoptosis in LUAD. The expression of TMED2 was higher in tumors or HCC827 cells. TMED2 knockdown inhibited LUAD development in vitro and in vivo and increased the levels of inflammatory factors via the TLR4/NF-κB signaling pathway. TMED2 was correlated with TME, immune score, TME-associated immune cells, their target markers, and some mechanisms and pathways, as determined using the TIMER2.0, GO, and KEGG assays. Conclusions TMED2 may regulate inflammation in LUAD through the TLR4/NF-κB signaling pathway and enhance the proliferation, development, and prognosis of LUAD by regulating inflammation, which provide a new strategy for treating LUAD by regulating inflammation.

show abstract

Upregulation of ADAM12 Is Associated With a Poor Survival and Immune Cell Infiltration in Colon Adenocarcinoma

Cited by 13 publications

References 50 publications

Identification of functional gene modules by integrating multi-omics data and known molecular interactions

Identification of functional gene modules by integrating multi-omics data and known molecular interactions

A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition

Transmembrane p24 trafficking protein 2 regulates inflammation through the TLR4/NF-κB signaling pathway in lung adenocarcinoma

Contact Info

Product

Resources

About