Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation and Immune Evasion

Ko, Kyung-Phil; Huang, Yuesheng; Zhang, Shengzhe; Zou, Gengyi; Kim, Bongjun; Zhang, Jie; Jun, Suckjoon; Martin, Cecilia; Dunbar, Karen J.; Efe, Gizem; Rustgi, Anil K.; Nakagawa, Hiroshi; Park, Jae-Il

doi:10.1053/j.gastro.2023.05.030

Cited by 22 publications

(10 citation statements)

References 53 publications

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“…We recently revealed genetic alterations of TP53 , NOTCH1 , and CDKN2A genes (PCN) induce tumorigenesis and immune evasion through releasing cytokine, CCL2, in organoid system. 50 To substantiate our findings, this PCN organoid tumor model can be used to evaluate IFN and IL signature signaling pathways in preclinical models. Moreover, we conducted additional analyses of the tumor epithelial cell transcriptomes of 69 patients, which will allow for the testing of the m3t4 and m2t3 relevant tumor models by connecting information acquired from epithelial cells and TME cells in our further study.…”

Section: Discussionsupporting

confidence: 55%

Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer

Ko,

Zhang,

Huang

et al. 2024

iScience

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Section: Discussionsupporting

confidence: 55%

Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer

Ko,

Zhang,

Huang

et al. 2024

iScience

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“…We recognize that ESCC is a multifactorial disease with various pathogenic genes, including but not limited to TP53, NOTCH1, CDKN2A, and COL6A3 (Gao et al, 2014;Li et al, 2019b;Liu et al, 2022;Ko et al, 2023). Our Gene Ontology (GO) enrichment analysis of differentially expressed genes highlighted "cell adhesion" as one of the top-ranked GO terms closely linked to cancer, with COL6A3 being among the genes significantly associated with this GO term.…”

Section: Discussionmentioning

confidence: 96%

DASES: a database of alternative splicing for esophageal squamous cell carcinoma

Chen,

Kuang,

Luan

et al. 2023

Front. Genet.

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Esophageal carcinoma ranks as the sixth leading cause of cancer-related mortality globally, with esophageal squamous cell carcinoma (ESCC) being particularly prevalent among Asian populations. Alternative splicing (AS) plays a pivotal role in ESCC development and progression by generating diverse transcript isoforms. However, the current landscape lacks a specialized database focusing on alternative splicing events (ASEs) derived from a large number of ESCC cases. Additionally, most existing AS databases overlook the contribution of long non-coding RNAs (lncRNAs) in ESCC molecular mechanisms, predominantly focusing on mRNA-based ASE identification. To address these limitations, we deployed DASES (http://www.hxdsjzx.cn/DASES). Employing a combination of publicly available and in-house ESCC RNA-seq datasets, our extensive analysis of 346 samples, with 93% being paired tumor and adjacent non-tumor tissues, led to the identification of 257 novel lncRNAs in esophageal squamous cell carcinoma. Leveraging a paired comparison of tumor and adjacent normal tissues, DASES identified 59,094 ASEs that may be associated with ESCC. DASES fills a critical gap by providing comprehensive insights into ASEs in ESCC, encompassing lncRNAs and mRNA, thus facilitating a deeper understanding of ESCC molecular mechanisms and serving as a valuable resource for ESCC research communities.

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“…Notch signaling also controls the generation and differentiation of efficient CD8 + T cells ( 41 ), and plays an important role in the exhaustion of CD8 + T cells. The regulation of Notch signaling pathway exhaustion has been reported in a variety of tumors, and previous studies have shown that Notch1 knockout plays an important role in promoting the formation of esophageal squamous cell carcinoma and immune escape ( 42 ). When Notch signaling is inhibited, the expression of PD-1 on the surface of CD8 + T cells is also inhibited ( 43 ), indicating that Notch signaling pathway has potential role in controlling the expression of PD-1 and reversing the function of CD8 + T cells.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of CD8+T cells related genes and exhaustion regulation of Notch signaling pathway in hepatocellular carcinoma

Pu,

Yu,

Liu

et al. 2024

Front. Immunol.

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Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion—a potential target for future immunotherapeutic interventions.

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Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation and Immune Evasion

Cited by 22 publications

References 53 publications

Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer

Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer

DASES: a database of alternative splicing for esophageal squamous cell carcinoma

Prognostic value of CD8+T cells related genes and exhaustion regulation of Notch signaling pathway in hepatocellular carcinoma

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