&lt;p&gt;Identification and Validation of MSX1 as a Key Candidate for Progestin Resistance in Endometrial Cancer&lt;/p&gt;

Yang, Linlin; Cui, Yunxia; Huang, Ting; Sun, Xiaojiang; Wang, Yudong

doi:10.2147/ott.s271494

Cited by 15 publications

(13 citation statements)

References 45 publications

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“…MSX1 is significantly upregulated in EC, which plays a crucial role in progestin resistance. Knockdown of MSX1 inhibited EMT and improved the therapeutic effect of progesterone (43). TNF-a, a proinflammatory cytokine, enhances TGF-b-induced EMT by activating the Smad2/3 signal (44).…”

Section: Discussionmentioning

confidence: 99%

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

et al. 2022

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BackgroundsEpithelial–mesenchymal transition (EMT) is a sequential process where tumor cells develop from the epithelial state to the mesenchymal state. EMT contributes to various tumor functions including initiation, propagating potential, and resistance to therapy, thus affecting the survival time of patients. The aim of this research is to set up an EMT-related prognostic signature for endometrial cancer (EC).MethodsEMT-related gene (ERG) expression and clinical data were acquired from The Cancer Genome Atlas (TCGA). The entire set was randomly divided into two sets, one for contributing the risk model (risk score) and the other for validating. Univariate and multivariate Cox proportional hazards regression analyses were applied to the training set to select the prognostic ERGs. The expression of 10 ERGs was confirmed by qRT-PCR in clinical samples. Then, we developed a nomogram predicting 1-/3-/5-year survival possibility combining the risk score and clinical factors. The entire set was stratified into the high- and low-risk groups, which was used to analyze the immune infiltrating, tumorigenesis pathways, and response to drugs.ResultsA total of 220 genes were screened out from 1,316 ERGs for their differential expression in tumor versus normal. Next, 10 genes were found to be associated with overall survival (OS) in EC, and the expression was validated by qRT-PCR using clinical samples, so we constructed a 10-ERG-based risk score to distinguish high-/low-risk patients and a nomogram to predict survival rate. The calibration plots proved the predictive value of our model. Gene Set Enrichment Analysis (GSEA) discovered that in the low-risk group, immune-related pathways were enriched; in the high-risk group, tumorigenesis pathways were enriched. The low-risk group showed more immune activities, higher tumor mutational burden (TMB), and higher CTAL4/PD1 expression, which was in line with a better response to immune checkpoint inhibitors. Nevertheless, response to chemotherapeutic drugs turned out better in the high-risk group. The high-risk group had higher N6-methyladenosine (m6A) RNA expression, microsatellite instability level, and stemness indices.ConclusionWe constructed the ERG-related signature model to predict the prognosis of EC patients. What is more, it might offer a reference for predicting individualized response to immune checkpoint inhibitors and chemotherapeutic drugs.

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Section: Discussionmentioning

confidence: 99%

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

et al. 2022

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“…Moreover, the methylation level of CpG island of MSX2 in gastric cancer tissues was found to be lower than in normal tissues and, therefore, MSX2 was upregulated in gastric cancer tissues (10,37). In endometrial cancer, the methylation status of MSX1 promoter was decreased, corresponding to its high expression (38). Histone acetyltransferase and histone deacetylase also regulate the expression of the MSX family.…”

Section: Dna Methylation and Chromatin Modificationmentioning

confidence: 99%

“…In particular, the expression of MSX1 is lower in multiple tumors such as breast cancer (82,83), high-grade serous epithelial ovarian cancer (67), gastric cancer (37), cervical cancer (68,84), testicular germ cell tumors (TGCTs) (69), malignant NK cell leukemia (34), glioblastoma (70), neuroblastoma (15), Wilms tumor (73) and Hodgkin lymphoma (35). Moreover, MSX1 expression is upregulated in T-ALL (48), mantle cell lymphoma (MCL) (39), acute myeloid leukemia (AML) (39), pituitary adenomas (71), melanoma (72), myxoid liposarcoma (MLS) (17), endometrial cancer (38). Whereas in colorectal cancer, compared to the adjacent normal tissues, MSX1 was shown to be down-regulated in COAD (9).…”

Section: The Roles Of Msx Family In Different Types Of Tumorsmentioning

confidence: 99%

A narrative review of the roles of muscle segment homeobox transcription factor family in cancer

Liu¹,

Huang²,

Han³

et al. 2021

Ann Transl Med

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Deregulation of many homeobox genes has been observed in various cancers and has caused functional implications in the tumor progression. In this review, we will focus on the roles of the human muscle segment homeobox (MSX) transcription factor family in the process of tumorigenesis. The MSX transcription factors, through complex downstream regulation mechanisms, are promoters or inhibitors of diverse cancers by participating in cell proliferation, cell invasion, cell metastasis, cell apoptosis, cell differentiation, drug resistance of tumors, maintenance of tumor stemness, and tumor angiogenesis. Moreover, their upstream regulatory mechanisms in cancers may include: gene mutation and chromosome aberration; DNA methylation and chromatin modification; regulation by non-coding RNAs; regulation by other transcription factors and post-translational modification. These mechanisms may provide a better understanding of why MSX transcription factors are abnormally expressed in tumors. Notably, intermolecular interactions and post-translational modification can regulate the transcriptional activity of MSX transcription factors. It is also crucial to know what affects the transcriptional activity of MSX transcription factors in tumors for possible interventions in them in the future. This systematic summary of the regulatory patterns of the MSX transcription factor family may help to further understand the mechanisms involved in transcriptional regulation and also provide new therapeutic approaches for tumor progression.

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“…MSX1 has been reported to be a transcriptional repressor that regulates the cell cycle, and is thought to play an important role in the development of EC [ 110 ]. Endometrial neoplasms have the greatest expression of MSX1, demonstrating the strong tissue specificity of this gene [ 111 ]. In vitro research by Yang et al revealed that MSX1 was substantially more elevated than other candidates in progestin-resistant Ishikawa-PR cells, and its knockdown improved the efficacy of progestin therapy [ 111 ].…”

Section: The Molecular Biomarkers Of Progestin Resistancementioning

confidence: 99%

Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma

Chen

Bai

et al. 2022

Cancers

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With a younger tendency in morbidity age, endometrial cancer (EC) incidence has grown year after year. Worse, even more commonly occurring is endometrial hyperplasia (EH), which is a precancerous endometrial proliferation. For young women with early EC and EH who want to preserve fertility, progestin therapy has been utilized as a routine fertility-preserving treatment approach. Nevertheless, progestin medication failure in some patients is mostly due to progestin resistance and side effects. In order to further analyze the potential mechanisms of progestin resistance in EH and EC, to provide theoretical support for effective therapeutic strategies, and to lay the groundwork for searching novel treatment approaches, this article reviews the current therapeutic effects of progestin in EH and EC, as well as the mechanisms and molecular biomarkers of progestin resistance, and systematically expounds on the potential therapeutic methods to overcome progestin resistance.

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<p>Identification and Validation of MSX1 as a Key Candidate for Progestin Resistance in Endometrial Cancer</p>

Cited by 15 publications

References 45 publications

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

Establishing a Prognostic Signature Based on Epithelial–Mesenchymal Transition-Related Genes for Endometrial Cancer Patients

A narrative review of the roles of muscle segment homeobox transcription factor family in cancer

Progestin Resistance and Corresponding Management of Abnormal Endometrial Hyperplasia and Endometrial Carcinoma

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