Endometrial Tumour Microenvironment

Casas-Arozamena, Carlos; Abal, Miguel

doi:10.1007/978-3-030-59038-3_13

Cited by 6 publications

(6 citation statements)

References 67 publications

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“…There is mounting evidence that the occurrence, growth and metastasis of UCEC are very intertwined with the immune microenvironment [34][35][36]. LAMP3 expression has been reported to influence the prognosis of lung adenocarcinoma by regulating the infiltration levels of B cells, dendritic cells, natural killer cells, and eosinophils [37].…”

Section: Discussionmentioning

confidence: 99%

LAMP3 is a potent uterine corpus endometrial carcinoma prognostic biomarker associated with immune behavior

Fu,

Zhou,

Geng

et al. 2024

Aging

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Background: Uterine corpus endometrial carcinoma (UCEC) is one of the most common gynecological malignancies and its incidence and mortality continue apace. Lysosome-associated membrane protein 3 (LAMP3) is the third member of the LAMP family and its overexpression has been described to be involved in the progression of breast, ovarian and cervical cancers, but there has been an absence of research focusing on its role in UCEC. Methods: WGCNA, TIMER, LinkedOmics, GSEA, Cytoscape, Kaplan-Meier plotter, GDC, GeneMANIA, cBioPortal, PDB, RNAinter, miRNet were applied in this research. Results: Our study uncovers that LAMP3 possesses higher expression levels in UCEC compared to normal tissues, and this differential expression profile is tightly aligned with clinical and pathological features, and patients demonstrating high LAMP3 expression tend to have a shorter survival expectancy. The high expression of LAMP3 is modulated by the designated ceRNA network. LAMP3 is engaged in UCEC progression by functioning in a variety of biological roles of relevance to immunity. Furthermore, we predicted several prospering drugs based on drug sensitivity. Finally, we also constructed possible docking patterns of LAMP3 with ABCA3, RAB9A, and SGTB. Conclusions: LAMP3 is a formidable biomarker for UCEC and could be a prospective candidate for the diagnosis, treatment and prognostic assessment of UCEC.

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Section: Discussionmentioning

confidence: 99%

LAMP3 is a potent uterine corpus endometrial carcinoma prognostic biomarker associated with immune behavior

Fu,

Zhou,

Geng

et al. 2024

Aging

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“…We demonstrate by in vitro assays that these cells secrete signals that induce the activation and pro-tumoral activities of ESC, acquiring CAF phenotypes. Specifically in endometrium, where the stromal component is very abundant and is found evolving the epithelial glands, stromal cells play a very important role in the growth, communication and differentiation of epithelial cells 17,18 . Supported by our results, this suggest that in EC, ARID1A may play a key role in TME regulation and tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…CAFs are the major component of the TME stroma and play a crucial role in tumor progression and aggressiveness 15,16 . Several works have demonstrated that tumor cells directly modulate activation and pro-tumoral function of CAFs through the secretion of paracrine signals 26,[33][34][35] and is found evolving the epithelial glands, stromal cells play a very important role in the growth, communication and differentiation of epithelial cells 17,18 . Supported by our results, this suggest that in EC, ARID1A may play a key role in TME regulation and tumor progression.…”

Section: Discussionmentioning

confidence: 99%

“…The soluble factors released by cancer and stroma cells constitute a secretory profile that have a primordial role in tumor progression and malignant phenotypes acquisition 14,15 . In EC the TME have a pivotal role in malignant and metastatic endometrial tumor transition, and it is increasingly postulated that microenvironment-derived signals are necessary to drive EC progression 17,18 . However, the knowledge about TME influence in EC progression raising limited.…”

Section: Introductionmentioning

confidence: 99%

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ARID1A-deficient cells promote endometrial carcinoma progression and dissemination by reprograming tumor microenvironment

Megino‐Luque

Matías‐Guiu

Eritja

2022

Preprint

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AT-rich interactive domain-containing protein 1A (ARID1A) loss-of-function mutation accompanied by a loss of ARID1A protein expression is frequently observed in endometrial carcinomas (EC). However, the mechanisms underlying this loss of ARID1A involved in the progression and dissemination of EC have been poorly studied and understood. Tumor microenvironment (TME) is reprogramed by cancer cells and have a high influence in aggressive behaviours of solid tumors. TME, and specially the stromal component, has a clear impact on the progression and aggressiveness of EC, but little is known about its activation, signalling and functions. Thus, the main aim of this study was to analyse the role of EC ARID1A loss in TME reprograming and its implication in endometrial tumor progression and aggressiveness. Here, using different endometrial in vitro and in vivo models, we show that endometrial tumor cells with altered expression of ARID1A promote the modulation and activation of the TME. We demonstrate that ARID1A depleted endometrial tumor cells induce aggressive behaviour in neighbouring endometrial tumor cells with wild-type ARID1A expression and the recruitment and activation of endometrial stromal cells (ESC). Interestingly, these pro-tumoral signals spread through the bloodstream supporting ARID1A wild-type EC cells aggressiveness. Finally, we show that ARID1A altered tumor cells display a different secretion profile and express significative high levels of chemokines in the TME. Taken together, our data demonstrate ARID1A depleted endometrial tumor cells reprograms TME promoting progression and dissemination of EC through chemokine secretion.

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“…The TME includes cancer cells and stromal cells. In ltrating immune cells including macrophages, natural killer cells, dendritic cells and lymphocytes in stromal cells regulate the progression and invasion of endometrial cancer by releasing growth factors, cytokines, and chemokines (11). Currently, the induction of ICD in tumor cells represents a novel approach to cancer treatment (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Signature identification based on immunogenic cell death-related lncRNAs to predict the prognosis and immune activity of patients with endometrial carcinoma

Yao

Zhang

Wei

et al. 2023

Preprint

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Background: Endometrial carcinoma (EC) is one of the most prevalent gynecologic malignancies and requires further classification for treatment and prognosis. Long non-coding RNAs (lncRNAs) and immunogenic cell death play a critical role in tumor progression. Nevertheless, the role of lncRNAs in immunogenic cell death in EC remains unclear. This study aimed to explore the role of immunogenic cell death (ICD) related-lncRNAs in EC via bioinformatics and establish a prognostic risk model based on the ICD related-lncRNAs. We also explored immune infiltration and immune cell function across prognostic groups and made treatment recommendations. Methods: A total of 552 EC samples and clinical data of 548 EC patients were extracted from The Cancer Genome Atlas (TCGA) database and UCSC Xena, respectively. A prognostic-related feature and risk model were developed using the least absolute shrinkage and selection operator (LASSO). Subtypes were classified with consensus cluster analysis and validated with t-Distributed Stochastic Neighbor Embedding (tSNE). Kaplan-Meier analysis was conducted to assess differences in survival. Infiltration by immune cells was estimated by ssGSEA, TIMER algorithm. By using the "pRRophetic" R package, the IC50 of drugs was compared among risk subgroups. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was performed to verify the expression of lncRNA in clinical EC tissues and cell lines. Result: In total, 16 immunogenic cell death-related lncRNAs with prognostic values were identified. Using SCARNA9, FAM198B-AS1, FKBP14-AS1, FBXO30-DT, LINC01943, and AL161431.1 as risk model, their predictive accuracy and discrimination were assessed. We divided EC patients into high-risk and low-risk groups based on the risk model. The analysis showed that the risk model was an independent prognostic factor. The prognosis of the high- and low-risk groups was different, and the overall survival (OS) of the high-risk group was lower. The low-risk group had higher immune cell infiltration and immune scores. Consensus clustering analysis divided the samples into four subtypes, of which cluster 4 had higher immune cell infiltration and immune scores. Conclusion:A prognostic signature composed of 6 immunogenic cell death related-lncRNAs in EC was established, and a risk model based on this signature can be used to predict the prognosis of patients with EC.

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Endometrial Tumour Microenvironment

Cited by 6 publications

References 67 publications

LAMP3 is a potent uterine corpus endometrial carcinoma prognostic biomarker associated with immune behavior

LAMP3 is a potent uterine corpus endometrial carcinoma prognostic biomarker associated with immune behavior

ARID1A-deficient cells promote endometrial carcinoma progression and dissemination by reprograming tumor microenvironment

Signature identification based on immunogenic cell death-related lncRNAs to predict the prognosis and immune activity of patients with endometrial carcinoma

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