Association of CSMD1 with Tumor Mutation Burden and Other Clinical Outcomes in Gastric Cancer

Wang, Xuning; Wang, Shixiang; Han, Yang; Xu, Maolin; Ke, Mu; Teng, Zhipeng; Huang, Pu; Diao, Ziyan; Yan, Yongfeng; Meng, Qingyu; Kuang, Yanshen; Zheng, Wei; Liu, Hongyi; Liu, Xuesong; Jia, Baoqing

doi:10.2147/ijgm.s325910

Cited by 4 publications

(6 citation statements)

References 27 publications

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“…A recent study in human ovarian cancers showed a significant correlation between CSMD3 mutation, elevated tumor mutation burden and shorter overall survival. Similar observations have been reported for CSMD1 in human gastric cancer [ 55 ], which was also mutated in multiple samples in the present study (11% of cases, 1/8 POS V595E and 3/28 UD V595E samples). The relatively high incidence of CSMD3 mutation in both human and canine UC, and the correlation with outcome in other human cancers, renders this gene a worthy candidate for an association with UC pathogenesis.…”

Section: Discussionsupporting

confidence: 92%

Whole exome sequencing analysis of canine urothelial carcinomas without BRAF V595E mutation: Short in-frame deletions in BRAF and MAP2K1 suggest alternative mechanisms for MAPK pathway disruption

et al. 2023

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Molecular profiling studies have shown that 85% of canine urothelial carcinomas (UC) harbor an activating BRAF V595E mutation, which is orthologous to the V600E variant found in several human cancer subtypes. In dogs, this mutation provides both a powerful diagnostic marker and a potential therapeutic target; however, due to their relative infrequency, the remaining 15% of cases remain understudied at the molecular level. We performed whole exome sequencing analysis of 28 canine urine sediments exhibiting the characteristic DNA copy number signatures of canine UC, in which the BRAF V595E mutation was undetected (UDV595E specimens). Among these we identified 13 specimens (46%) harboring short in-frame deletions within either BRAF exon 12 (7/28 cases) or MAP2K1 exons 2 or 3 (6/28 cases). Orthologous variants occur in several human cancer subtypes and confer structural changes to the protein product that are predictive of response to different classes of small molecule MAPK pathway inhibitors. DNA damage response and repair genes, and chromatin modifiers were also recurrently mutated in UDV595E specimens, as were genes that are positive predictors of immunotherapy response in human cancers. Our findings suggest that short in-frame deletions within BRAF exon 12 and MAP2K1 exons 2 and 3 in UDV595E cases are alternative MAPK-pathway activating events that may have significant therapeutic implications for selecting first-line treatment for canine UC. We developed a simple, cost-effective capillary electrophoresis genotyping assay for detection of these deletions in parallel with the BRAF V595E mutation. The identification of these deletion events in dogs offers a compelling cross-species platform in which to study the relationship between somatic alteration, protein conformation, and therapeutic sensitivity.

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Section: Discussionsupporting

confidence: 92%

Whole exome sequencing analysis of canine urothelial carcinomas without BRAF V595E mutation: Short in-frame deletions in BRAF and MAP2K1 suggest alternative mechanisms for MAPK pathway disruption

et al. 2023

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“…A body of evidence showed that gene mutations can be prognostic indicators of tumors and cancers [49][50][51]. For example, FREM2 [48], CSMD1 [52], and ARID1A [53] mutations, have been identified as potential prognostic biomarkers of colorectal cancer, gastric cancer, and hepatocellular carcinoma, respectively. Furthermore, there is evidence showing the association of genetic mutations in TLR3, TNFSF10, and MET, with the risk and survival of human cancer [54][55][56].…”

Section: Evidence-based Complementary and Alternative Medicinementioning

confidence: 99%

Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer

Wang

Han

2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Biomarkers for pancreatic cancer (PCa) prognosis provide evidence for improving the survival outcome of this disease. This study aimed to identify a prognostic risk model based on gene expression profiling of microarray bioinformatics analysis. Methods. Prognostic immune genes in the TCGA-PAAD cohort were identified using the univariate Cox regression and Kaplan–Meier survival analysis. Multivariate Cox regression (stepAIC) was used to identify prognostic genes from the top 20 hub genes in the protein-protein interaction (PPI) network. A prognostic risk model was established and its performance in predicting the overall survival in PCa was validated in GSE62452. Gene mutations and infiltration immune cells in PCa tumors were analyzed using online databases. Results. Univariate Cox regression and Kaplan–Meier survival analyses identified 128 prognostic genes. Multivariate Cox regression (stepAIC) identified five prognostic genes (PLCG1, MET, TNFSF10, CXCL9, and TLR3) out of the 20 hub genes in the PPI network. A prognostic risk model was established using the signature of five genes. This model had moderate to high accuracies (AUC > 0.700) in predicting 3-year and 5-year overall survival in TCGA and GSE62452 cohorts. The Kaplan–Meier survival analysis showed that high-risk scores were correlated with poor survival outcomes in PCa ( p < 0.05 ). Also, mutations in the five genes were related to poor survival. The five genes were related to multiple immune cells. Conclusions. The prognostic risk model was significantly correlated with the survival in PCa patients. This model modulated PCa tumor progression and prognosis by regulating immune cell infiltration.

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“…Following that, it showed that several immune-related signalling pathways were upregulated in the CSMD1 -mut samples; that there was a higher proportion of anti-tumour immune cells, such as CD4+ Th1 cells, NK cells, M1 macrophage cells, and PDC; a lower proportion of tumour-promoting immune cells, such as Treg cells, M2 macrophage cells, and endothelial cells; and that PD-L1 was upregulated [ 73 ]. Another GC study confirmed the association between CSMD1 mutation with TMB and high PDL1 expression and increased survival supporting the potential of CSMD1 as a biomarker for assessing immune checkpoint inhibitor therapy in GC patients [ 74 ].…”

Section: Csmd1 Functionmentioning

confidence: 84%

“…Elucidating the relationship of CSMD1 with the aforementioned diseases in this review may be important in terms of both treatment and diagnosis in the future. Recent studies have revealed a possible role for CSMD1 in immunotherapy for some cancer types [ 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. The determination of the factors affecting the expression of CSMD1 and the clarification of the signalling pathways it affects will increase the clinical utility of CSMD1.…”

Section: Discussionmentioning

confidence: 99%

“…This study also found CSMD1 wild-type oesophageal cancer patients were more susceptible to paclitaxel chemotherapy [ 71 ]. It has shown that CSMD1 is dramatically downregulated in gastric cancer (GC) tissues compared to normal tissues via RT-PCR, and the overexpression of microRNA-10b, a direct target of CSMD1 in GC cells, was found to increase GC cell vitality, migration, and invasion [ 72 , 73 , 74 ]. Another study discovered that miR-642b-3p acts as an oncomiR that promotes tumour progression in GC by repressing CSMD1 expression and inactivating the Smad signalling pathway, which could contribute to the development of potential therapies for GC treatment [ 75 ].…”

Section: Csmd1 Functionmentioning

confidence: 99%

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The Diverse Role of CUB and Sushi Multiple Domains 1 (CSMD1) in Human Diseases

Ermis

Bell

2022

Genes

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CUB and Sushi Multiple Domains 1 (CSMD1), a tumour suppressor gene, encodes a large membrane-bound protein including a single transmembrane domain. This transmembrane region has a potential tyrosine phosphorylation site, suggesting that CSMD1 is involved in controlling cellular functions. Although the specific mechanisms of action for CSMD1 have not yet been uncovered, it has been linked to a number of processes including development, complement control, neurodevelopment, and cancer progression. In this review, we summarise CSMD1 functions in the cellular processes involved in the complement system, metastasis, and Epithelial mesenchymal transition (EMT) and also in the diseases schizophrenia, Parkinson’s disease, and cancer. Clarifying the association between CSMD1 and the aforementioned diseases will contribute to the development of new diagnosis and treatment methods for these diseases. Recent studies in certain cancer types, e.g., gastric cancer, oesophageal cancer, and head and neck squamous cell carcinomas, have indicated the involvement of CSMD1 in response to immunotherapy.

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Association of CSMD1 with Tumor Mutation Burden and Other Clinical Outcomes in Gastric Cancer

Cited by 4 publications

References 27 publications

Whole exome sequencing analysis of canine urothelial carcinomas without BRAF V595E mutation: Short in-frame deletions in BRAF and MAP2K1 suggest alternative mechanisms for MAPK pathway disruption

Whole exome sequencing analysis of canine urothelial carcinomas without BRAF V595E mutation: Short in-frame deletions in BRAF and MAP2K1 suggest alternative mechanisms for MAPK pathway disruption

Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer

The Diverse Role of CUB and Sushi Multiple Domains 1 (CSMD1) in Human Diseases

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