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:10.1101/2022.10.13.512143

Cited by 3 publications

(3 citation statements)

References 60 publications

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“…Currently, monoclonal antibodies targeting immune checkpoint molecules have achieved signi cant breakthroughs in cancer therapy. Taking CCL2 and PD-L1 as examples, their targeting has shown encouraging results in the treatment of ESCC [37]. We found that there were notable distinctions between the expression levels of lncRNA MIR210HG at high and low levels in different immunological checkpoints.…”

Section: Discussionmentioning

confidence: 82%

Based on in vivo and in vitro experiments validation: lncRNA MIR210HG inhibits esophageal squamous cell carcinoma and correlates with autophagy and apoptosis

Wang,

Zhang,

Song

et al. 2024

Preprint

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Background: Esophageal squamous cell carcinoma (ESCC) is a prevalent cancer that affects many people. The high death rate is still caused by ineffective early diagnostic and treatment methods. While the long non-coding RNA MIR210HG has been associated with several malignancies, its role in ESCC remains unclear. This study aims to explore the function of lncRNA MIR210HG in the pathogenesis of ESCC. Methods: We performed a pan-cancer analysis of lncRNA MIR210HG expression across various malignancies using the TCGA database, and we looked into the relationship between MIR210HG and the predictive survival of patients with ESCC. Moreover, we investigated MIR210HG's biological role using GO, KEGG, and GSEA enrichment analysis. In relation to MIR210HG, we also examined immune cell infiltration, immune checkpoint expression levels, tumor microenvironment (TME) features, and therapy sensitivity. To get more insight into the connection between lncRNA MIR210HG and ESCC, we assessed related gene and protein expression using Western blotting and RT-qPCR. To evaluate the proliferation, invasion, migration, apoptosis, and autophagy of ESCC cells, various techniques were employed, including EdU proliferation tests, wound healing assays, cell colony formation, transwell assays, flow cytometry, and an established xenograft mouse model. Results: lncRNA MIR210HG was found to be underexpressed in ESCC, and patients with higher expression levels of lncRNA MIR210HG exhibited increased survival rates. Overexpression of the lncRNA MIR210HG inhibited the proliferation, invasion, and migration of ESCC cells both in vitro and in vivo. Moreover, lncRNA MIR210HG was positively correlated with the P53 signaling pathway and influenced apoptosis and autophagy. Conclusion: In summary, lncRNA MIR210HG is a key gene affecting prognosis and immunity in ESCC and may influence apoptosis and autophagy through the P53 signaling pathway, offering new insights for the treatment of ESCC.

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Section: Discussionmentioning

confidence: 82%

Based on in vivo and in vitro experiments validation: lncRNA MIR210HG inhibits esophageal squamous cell carcinoma and correlates with autophagy and apoptosis

Wang,

Zhang,

Song

et al. 2024

Preprint

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“…We used Adeno-Cre virus to treat Kras LSL-G12D/+ ; Trp53 fl/fl organoids. The protocol was previously described (Ko et al, 2022; Ko et al, 2023). The cells were first dissociated from GOs as described in the organoid passaging protocol (step 1-14) .…”

Section: Methodsmentioning

confidence: 99%

CDH1 loss promotes diffuse-type gastric cancer tumorigenesis via epigenetic reprogramming and immune evasion

Zou

Huang

Zhang

et al. 2023

Preprint

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Diffuse-type gastric adenocarcinoma (DGAC) is lethal cancer often diagnosed late and resistant to therapeutics. Although hereditary DGAC is mainly characterized by mutations in the CDH1 gene encoding E-cadherin, the impact of E-cadherin inactivation on sporadic DGAC tumorigenesis remains elusive. We found that CDH1 inactivation occurs only subset of DGAC patient tumors. Unsupervised clustering of single-cell transcriptomes of DGAC patient tumors identified two subtypes of DGACs: DGAC1 and DGAC2. The DGAC1 is mainly characterized by CDH1 loss and exhibits distinct molecular signatures and aberrantly activated DGAC-related pathways. Unlike DGAC2 lacking immune cell infiltration in tumors, DGAC1 tumor is enriched with exhausted T cells. To demonstrate the role of CDH1 loss in DGAC tumorigenesis, we established a genetically engineered murine gastric organoid (GOs; Cdh1 knock-out [KO], KrasG12D, Trp53 KO [EKP]) model recapitulating human DGAC. In conjunction with KrasG12D, Trp53 KO (KP), Cdh1 KO is sufficient to induce aberrant cell plasticity, hyperplasia, accelerated tumorigenesis, and immune evasion. Additionally, EZH2 was identified as a key regulon promoting CDH1 loss-associated DGAC tumorigenesis. These findings underscore the significance of comprehending the molecular heterogeneity of DGAC and its potential implication for personalized medicine to DGAC patients with CDH1 inactivation.

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“…1 Recent evidence has expanded on this possibility, suggesting that loss of NOTCH1, TP53, and CDKN2A promote an immunosuppressive niche enriched by exhausted T cells and M2 macrophages via the CCL2/CCR2 axis. 72 ESCC3 is characterized by activating mutations of the PI3K pathway. 1…”

Section: Squamous Cell Cancermentioning

confidence: 99%

Advances in diagnosis and management of cancer of the esophagus

Deboever,

Jones,

Yamashita

et al. 2024

BMJ

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Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett’s esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.

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

Cited by 3 publications

References 60 publications

Based on in vivo and in vitro experiments validation: lncRNA MIR210HG inhibits esophageal squamous cell carcinoma and correlates with autophagy and apoptosis

Based on in vivo and in vitro experiments validation: lncRNA MIR210HG inhibits esophageal squamous cell carcinoma and correlates with autophagy and apoptosis

CDH1 loss promotes diffuse-type gastric cancer tumorigenesis via epigenetic reprogramming and immune evasion

Advances in diagnosis and management of cancer of the esophagus

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