The metabolic genomic atlas reveals potential drivers and clinically relevant insights into the etiology of esophageal squamous cell carcinoma

Liu, Xuesong; Hong, Ruoxi; Du, Peina; Yang, Di; He, Minghao; Wu, Qingnan; Li, Lin; Wang, Yan; Chen, Jie; Min, Qingjie; Li, Jinting; Zhang, Weimin; Zhan, Qimin

doi:10.7150/thno.70814

Cited by 3 publications

(2 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Microsomal glutathione S-transferase 3 (MGST3) is a member of the glutathione S-transferase family, which is involved in detoxification [ 45 ]. A previous study showed that overexpression of MGST3 significantly promotes the progression of esophageal squamous cell carcinoma [ 46 ]. Gem nuclear organelle-associated protein 6 (GEMIN6) is a component of the survival of the motor neuron (SMN) complex.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analyses of a CD8+ T cell infiltration related gene signature with regard to the prediction of prognosis and immunotherapy response in lung squamous cell carcinoma

et al. 2023

View full text Add to dashboard Cite

Lung squamous cell carcinoma (LUSC) is associated with a worse prognosis than other histological subtypes of non-small cell lung cancer. Due to the vital role of CD8+ T cells in anti-tumor immunity, the characterization of CD8+ T cell infiltration-related (CTLIR) gene signature in LUSC is worthy of in-depth exploration. In our study, tumor tissues of LUSC patients from Renmin Hospital of Wuhan University were stained by multiplex immunohistochemistry to evaluate the density of infiltrated CD8+ T cells and explore the correlation with immunotherapy response. We found that the proportion of LUSC patients who responded to immunotherapy was higher in the high density of CD8+ T cell infiltration group than in the low density of CD8+ T cell infiltration group. Subsequently, we collected bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) database. The abundance of infiltrating immune cells in LUSC patients was analyzed by using CIBERSORT algorithm, and weighted correlation network analysis was performed to identify the co-expressed gene modules related to CD8+ T cells. We then developed a prognostic gene signature based on CD8+ T cell co-expressed genes and calculated the CTLIR risk score, which stratified LUSC patients into high-risk and low-risk groups. With univariate and multivariate analyses, the gene signature was identified as an independent prognostic factor in LUSC patients. The overall survival of LUSC patients in the high-risk group was significantly shorter than that of the low-risk group in the TCGA cohort, which was validated in Gene Expression Omnibus datasets. We analyzed immune cell infiltration in the tumor microenviroment and found fewer CD8+ T cells and more regulatory T cell infiltration in the high-risk group, which is characterized as an immunosuppressive phenotype. Furthermore, the LUSC patients in the high-risk group were predicted to have a better response to immunotherapy than those in the low-risk group when treated with PD-1 and CTLA4 inhibitors. In conclusion, we performed a comprehensive molecular analysis of the CTLIR gene signature in LUSC and constructed a risk model for LUSC patients to predict prognosis and immunotherapy response.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive analyses of a CD8+ T cell infiltration related gene signature with regard to the prediction of prognosis and immunotherapy response in lung squamous cell carcinoma

et al. 2023

View full text Add to dashboard Cite

show abstract

“…As for the potential correlation between synapse and carcinogenesis, several researchers found that tumor cells can form pseudo-tripartite synapses with neurons to increase tumor growth ( 48 – 50 ). Genetic alterations in non-neural/neural synapse systems were reported to contribute to the development of ESCC ( 51 ). The synaptic adhesion-like molecule (SALM) was found to be a potential prognostic biomarker in GC patients ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Rare variants confer shared susceptibility to gastrointestinal tract cancer risk

Zheng

Wang

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

BackgroundCancers arising within the gastrointestinal tract are complex disorders involving genetic events that cause the conversion of normal tissue to premalignant lesions and malignancy. Shared genetic features are reported in epithelial-based gastrointestinal cancers which indicate common susceptibility among this group of malignancies. In addition, the contribution of rare variants may constitute parts of genetic susceptibility.MethodsA cross-cancer analysis of 38,171 shared rare genetic variants from genome-wide association assays was conducted, which included data from 3,194 cases and 1,455 controls across three cancer sites (esophageal, gastric and colorectal). The SNP-level association was performed by multivariate logistic regression analyses for single cancer, followed by association analysis for SubSETs (ASSET) to adjust the bias of overlapping controls. Gene-level analyses were conducted by SKAT-O, with multiple comparison adjustments by false discovery rate (FDR). Based on the significant genes indicated by SKATO analysis, pathways analysis was conducted using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases.ResultsMeta-analysis in three gastrointestinal (GI) cancers identified 13 novel susceptibility loci that reached genome-wide significance (PASSET< 5×10-8). SKAT-O analysis revealed EXOC6, LRP5L and MIR1263/LINC01324 to be significant genes shared by GI cancers (Padj<0.05, PFDR<0.05). Furthermore, GO pathway analysis identified significant enrichment of synaptic transmission and neuron development pathways shared by all three cancer types.ConclusionRare variants and the corresponding genes potentially contribute to shared susceptibility in different GI cancer types. The discovery of these novel variants and genes offers new insights for the carcinogenic mechanisms and missing heritability of GI cancers.

show abstract

MGST3 regulates BACE1 protein translation and amyloidogenesis by controlling the RGS4-mediated AKT signaling pathway

Pu,

Yang,

Pan

et al. 2024

Journal of Biological Chemistry

View full text Add to dashboard Cite

The metabolic genomic atlas reveals potential drivers and clinically relevant insights into the etiology of esophageal squamous cell carcinoma

Cited by 3 publications

References 73 publications

Comprehensive analyses of a CD8+ T cell infiltration related gene signature with regard to the prediction of prognosis and immunotherapy response in lung squamous cell carcinoma

Comprehensive analyses of a CD8+ T cell infiltration related gene signature with regard to the prediction of prognosis and immunotherapy response in lung squamous cell carcinoma

Rare variants confer shared susceptibility to gastrointestinal tract cancer risk

MGST3 regulates BACE1 protein translation and amyloidogenesis by controlling the RGS4-mediated AKT signaling pathway

Contact Info

Product

Resources

About