CARD11 is a prognostic biomarker and correlated with immune infiltrates in uveal melanoma

Shi, Xueying; Xia, Shilin; Chu, Yan; Yang, Nan; Zheng, Jingyuan; Chen, Qianyi; Zeng, Fen; Jiang, Yuankuan; Fang, Shifeng; Lin, Jingrong

doi:10.1371/journal.pone.0255293

Cited by 8 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CTF1 has been part of a previously defined UM-immune-related three-gene signature on TCGA data [30]. CARD11 was detected as a prognostic marker, with high expression associated to poor OS in the TCGA UVM dataset; in particular, metastatic patients had higher expression of this gene [31]; however, the MGS based on a larger dataset [17] assigned a protective effect to this gene, probably due to a set of patients with limited survival, metastatic disease and low CARD11 expression (Figures S2 and S3). HTR2B, TNFRSF19 and PTGER4 were previously found to be overexpressed in class 2 tumors (metastatic) [32]; in particular, TCGA UVM patients with high PTGER4 expression had worse survival [33].…”

Section: Integration Of Resultsmentioning

confidence: 99%

Machine Learning Methods for Gene Selection in Uveal Melanoma

Reggiani,

El Rashed,

Petito

et al. 2024

IJMS

View full text Add to dashboard Cite

Uveal melanoma (UM) is the most common primary intraocular malignancy with a limited five-year survival for metastatic patients. Limited therapeutic treatments are currently available for metastatic disease, even if the genomics of this tumor has been deeply studied using next-generation sequencing (NGS) and functional experiments. The profound knowledge of the molecular features that characterize this tumor has not led to the development of efficacious therapies, and the survival of metastatic patients has not changed for decades. Several bioinformatics methods have been applied to mine NGS tumor data in order to unveil tumor biology and detect possible molecular targets for new therapies. Each application can be single domain based while others are more focused on data integration from multiple genomics domains (as gene expression and methylation data). Examples of single domain approaches include differentially expressed gene (DEG) analysis on gene expression data with statistical methods such as SAM (significance analysis of microarray) or gene prioritization with complex algorithms such as deep learning. Data fusion or integration methods merge multiple domains of information to define new clusters of patients or to detect relevant genes, according to multiple NGS data. In this work, we compare different strategies to detect relevant genes for metastatic disease prediction in the TCGA uveal melanoma (UVM) dataset. Detected targets are validated with multi-gene score analysis on a larger UM microarray dataset.

show abstract

Section: Integration Of Resultsmentioning

confidence: 99%

Machine Learning Methods for Gene Selection in Uveal Melanoma

Reggiani,

El Rashed,

Petito

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…In addition, CARMA1 can activate NF-κB through the CBM complex to cause excessive cell proliferation, invasion and metastasis and tumor angiogenesis, which is an important cause of autoimmune diseases or of lymphatic hematopoietic system tumors (19)(20)(21). Furthermore, high CARD11 expression in uveal melanoma is associated with poor overall survival and CARD11 is associated with autophagy, cell senescence and apoptosis (22). EMT is a cellular process by which epithelial cells gain a mesenchymal phenotype through specific changes in gene expression (23).…”

Section: Discussionmentioning

confidence: 99%

KLF5‑mediated expression of CARD11 promotes the progression of gastric cancer

Li¹,

Li²,

Li³

et al. 2023

Exp Ther Med

View full text Add to dashboard Cite

Caspase recruitment domain-containing protein 11 (CARD11) has been reported as functioning in multiple types of cancers. In the present study, the role and mechanism of CARD11 in gastric cancer was investigated. First, CARD11 expression in gastric cancer tissues and the association of CARD11 with overall survival were analyzed by the encyclopedia of RNA interactomes database. CARD11 expression in gastric cancer cells was detected by western blotting and reverse transcription-quantitative PCR analyses. After CARD11 silencing, cell proliferation was evaluated by Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining and flow cytometry analysis. Wound healing and Transwell assays were used to measure the capacities of cell migration and invasion. Additionally, the expression levels of epithelial-mesenchymal transition (EMT)-related proteins and mTOR-related proteins were detected by western blot analysis. HumanTFDB predicted the binding of the transcription factor Krüppel-like factor 5 (KLF5) to the CARD11 promoter, which was confirmed by dual luciferase reporter and chromatin immunoprecipitation assays. To explore the regulatory effects between KLF5 and CARD11, KLF5 was overexpressed to perform the rescue experiments in gastric cancer cells with CARD11 silencing. Results revealed that CARD11 was highly expressed in gastric cancer and was associated with poor prognosis. CARD11 interference inhibited the proliferation of gastric cancer cells and induced cell cycle arrest. Additionally, CARD11 silencing suppressed the migration, invasion and EMT of gastric cancer cells, accompanied by upregulated E-cadherin expression and downregulated N-cadherin and vimentin expression. Moreover, the transcription factor KLF5 positively regulated the transcription of CARD11 in gastric cancer. KLF5 overexpression reversed the effects of interference of CARD11 expression in gastric cancer cells to promote their proliferation, migration, invasion and EMT. KLF5 overexpression also led to a reduction in cell cycle arrest. Finally, interference of CARD11 expression suppressed the mTOR pathway, which was activated by KLF5. In conclusion, KLF5-mediated CARD11 promoted the proliferation, migration and invasion of gastric cancer cells.

show abstract

“…Mutations in CARD11 are associated with apoptosis and abnormal activation of NF-KappaB, which may lead to compromised adaptive immunity, leading to various immunological diseases in patients ( 29 ). High expression of CARD11 is associated with shorter overall survival in uveal melanoma ( 30 ). IRS1 encodes a protein that is phosphorylated by the insulin receptor tyrosine kinase.…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of intracranial teratomas using whole genome sequencing

et al. 2022

View full text Add to dashboard Cite

BackgroundIntracranial teratoma is a rare neoplasm of the central nervous system, often classified into mature and immature types and occurs mainly in children and adolescents. To date, there has been no comprehensive genomic characterization analysis of teratoma due to its rarity of the cases.MethodsForty-six patients with intracranial teratomas were collected and 22 of them underwent whole-exome sequencing, including 8 mature teratomas and 14 immature teratomas. A comprehensive analysis was performed to analyze somatic mutations, copy number variants (CNVs), mutational signatures, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in our cohort.ResultsThe most common somatic mutated gene in intracranial teratomas was CARD11 (18%) and IRS1 (18%), followed by PSMD11, RELN, RRAS2, SMC1A, SYNE1 and ZFHX3, with mutation rates of 14% for the latter six genes. Copy number variation was dominated by amplification, among which ARAF (50%), ATP2B3 (41%), GATA1 (41%), ATP6AP1 (36%), CCND2 (36%) and ZMYM3 (36%) were the most frequently amplified genes. Copy number deletion of SETDB2 and IL2 only appeared in immature teratoma (43% and 36%, respectively), but not in mature teratoma (p = 0.051 and 0.115, respectively). Prognostic analysis showed that TP53 mutations might be associated with poor prognosis of intracranial teratomas patients.ConclusionsOur study revealed the genetic characteristics of intracranial teratoma which might be valuable for guiding future targeted therapies.

show abstract

CARD11 is a prognostic biomarker and correlated with immune infiltrates in uveal melanoma

Cited by 8 publications

References 43 publications

Machine Learning Methods for Gene Selection in Uveal Melanoma

Machine Learning Methods for Gene Selection in Uveal Melanoma

KLF5‑mediated expression of CARD11 promotes the progression of gastric cancer

Genomic characterization of intracranial teratomas using whole genome sequencing

Contact Info

Product

Resources

About