The Clinical Significance of Forkhead Box M1 in Esophageal Squamous Cell Carcinoma Tissues: A Study Based on In-house Immunohistochemistry, RNA-sequencing, and Data Mining

Abstract BackgroundEsophageal squamous cell carcinoma (ESCC) ranks the sixth in mortality rates in cancers due to a lack of a specific target of diagnosis and treatment in the early stages. Although Forkhead box M1 (FOXM1) has been reported to be differentially expressed in ESCC, its clinical role and function in ESCC remained unclarified.MethodsData from our hospital and public databases (n = 1906) were combined to estimate how FOXM1 overexpression showed its discriminatory ability between ESCC and non-ESCC esophageal tissues. Downstream targets of FOXM1 were predicted by using Cistrome database. Functional enrichment analyses were performed to explore the potential signaling pathways related to FOXM1 in ESCC. Based on the available clinical parameters, we investigated the prognosis potential of FOXM1 and its targets.ResultsThe pooled standard mean difference (SMD) for FOXM1 is 2.62 (95% CI: 2.08–3.16), indicating that FOXM1 is upregulated in ESCC. FOXM1 has an extremely high discrimination potential in ESCC because the area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) is 0.99 (95% CI: 0.97–0.99). A total of 168 downstream targets were identified, and nine hub genes were screened from them. We found that FOXM1 and its targets were significantly enriched in the cell cycle. Additionally, the correlation between FOXM1 and clinical parameters had not been observed, except for age.ConclusionsFOXM1 is upregulated in ESCC and has an extremely high discrimination potential in ESCC.

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Significance of mucin type glucosaminyl (N-acetyl) transferase 3 expression in lung squamous cell carcinoma

10.21203/rs.3.rs-142867/v1 ◽

2021 ◽

Author(s):

Yu-Jun Chen ◽

Li Gao ◽

Rui Zhang ◽

Gang Chen ◽

Zhen-bo Feng ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Methylation Level ◽

Lung Squamous Cell Carcinoma ◽

Enrichment Analysis ◽

Progression Free Survival ◽

Genetic Mutation ◽

Functional Enrichment ◽

Standard Mean Difference

Abstract Background: The clinical significance and role of glycan synthase glucosamine (N-acetyl) transferase 3 (GCNT3) has not been investigated in lung squamous cell carcinoma (LUSC).Materials & Methods: In the present study, multiple detection technologies including tissue microarrays, external microarrays and RNA-seq were adopted for evaluating the clinic-pathological significance of GCNT3 in 1632 LUSC samples and 1478 non-cancer samples. Standard mean difference and hazard ratio value were calculated from all included datasets for assessing differential expression and prognostic value of GCNT3 in LUSC. The molecular basis underlying GCNT3 in LUSC was also explored through methylation level, genetic mutation and functional enrichment analysis of GCNT3-correlated genes in LUSC. Results: GCNT3 was obviously upregulated in LUSC samples. GCNT3 overexpression exerted unfavorable impact on the progression-free survival and overall survival of LUSC patients from GSE29013. The mRNA expression of GCNT3 was negatively correlated with methylation level of GCNT3 in LUSC and the predominant type of genetic alteration for GCNT3 in LUSC was mRNA high. Genes correlated with GCNT3 in LUSC mainly assembled in pathways such as adherens junction, p53 signaling pathway, protein digestion and absorption pathway. Conclusions: In conclusion, overexpressed GCNT3 had clinical potential as therapeutic target for LUSC.

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Forkhead box M1 expression in pulmonary squamous cell carcinoma: correlation with clinicopathologic features and its prognostic significance

Human Pathology ◽

10.1016/j.humpath.2008.10.001 ◽

2009 ◽

Vol 40 (4) ◽

pp. 464-470 ◽

Cited By ~ 46

Author(s):

Doo Kyung Yang ◽

Choon Hee Son ◽

Soo Keol Lee ◽

Phil Jo Choi ◽

Kyung Eun Lee ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Significance ◽

Clinicopathologic Features ◽

Forkhead Box ◽

Forkhead Box M1

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Cytoplasmic Forkhead Box M1 (FoxM1) in Esophageal Squamous Cell Carcinoma Significantly Correlates with Pathological Disease Stage

World Journal of Surgery ◽

10.1007/s00268-011-1302-5 ◽

2011 ◽

Vol 36 (1) ◽

pp. 90-97 ◽

Cited By ~ 25

Author(s):

Marco K. C. Hui ◽

Kwok Wah Chan ◽

John M. Luk ◽

Nikki P. Lee ◽

Yvonne Chung ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Disease Stage ◽

Forkhead Box ◽

Forkhead Box M1 ◽

Pathological Disease

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Clinical Value and Potential Mechanism of miRNA-33a-5p in Lung Squamous Cell Carcinoma

Analytical Cellular Pathology ◽

10.1155/2021/6614331 ◽

2021 ◽

Vol 2021 ◽

pp. 1-20

Author(s):

Xiang-Ming Wang ◽

Shang-Wei Chen ◽

Gang Chen ◽

Hua-Fu Zhou ◽

Ting-Qing Gan ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Target Genes ◽

Lung Squamous Cell Carcinoma ◽

Functional Enrichment ◽

Ppi Network ◽

Summary Receiver Operating Characteristic ◽

Potential Target ◽

Standard Mean Difference

This study is aimed at thoroughly exploring the expression status, clinical significance, and underlying molecular mechanism of miRNA-33a-5p in lung squamous cell carcinoma (LUSC). Here, we detected miRNA-33a-5p in 20 samples from patients with LUSCs and 20 matching non-LUSC specimens by in-house quantitative real-time PCR (RT-qPCR). Relationship between miRNA-33a-5p expression and clinicopathological traits was investigated from materials derived from miRNA sequencing and miRNA microarrays. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to evaluate the integrated expression value of miRNA-33a-5p in LUSC. Twelve online platforms were applied to select potential target genes of miRNA-33a-5p. The differentially expressed genes (DEGs) of LUSC and the candidate target genes of miRNA-33a-5p were overlapped to acquire a set of specific genes for further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein–protein interaction (PPI) network. miRNA-33a-5p overexpressed in LUSC was supported by 706 LUSC and 261 non-LUSC samples gathering from RT-qPCR, miRNA-seq, and public miRNA microarrays. The pooled SMD was 0.56 (95% CI: -0.01-1.05), and the area under the curve (AUC) of the SROC was 0.78 (95% CI: 0.74-0.82). A total of 240 genes were identified as potential target genes of miRNA-33a-5p for functional enrichment analyses; the results suggested that these target genes may participate in several vital biological processes that promote the proliferation and progression of LUSC. miRNA-33a-5p may play an essential role in the occurrence and development of LUSC by targeting hub genes (ETS1, EDNRB, CYR61, and LRRK2) derived from the PPI network. In summary, our results indicated that miRNA-33a-5p may contribute as a prospective therapeutic target in LUSC.

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Lentiviral RNA interference‑mediated downregulation of Forkhead box M1 expression suppresses growth of oral squamous cell carcinoma in�vitro

Oncology Letters ◽

10.3892/ol.2018.9536 ◽

2018 ◽

Author(s):

Jing Qiu ◽

Juan Zhao ◽

Anjun Zuo ◽

Lan Liu ◽

Qiaoqiao Liu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Rna Interference ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Forkhead Box ◽

Forkhead Box M1

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Isoliquiritigenin Inhibits Proliferation and Induces Apoptosis in Tongue Squamous Cell Carcinoma by Modulating miR-21/FOXG1 Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.17:463-469 ◽

2019 ◽

Vol 17 (4) ◽

pp. 463-469

Author(s):

Hou Deqiang ◽

Gao Yufeng ◽

Bai Ning ◽

Dong Yu

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Carcinoma Cells ◽

Tongue Squamous Cell Carcinoma ◽

Luciferase Assay ◽

Forkhead Box ◽

Proliferation And Apoptosis ◽

Mrna And Protein Expression ◽

Induced Apoptosis

Isoliquiritigenin is a flavonoid commonly found in liquorice and has been identified as a potent anti-tumor agent. The aim of this study was to investigate whether isoliquiritigenin regulates the proliferation and apoptosis of tongue squamous cell carcinoma cells by regulating forkhead box G1 expression via miR-21. MTT assay and flow cytometry were used to analyze cell proliferation and apoptosis, respectively. Quantitative real time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels, respectively. The relationship between miR-21 and forkhead box G1 was detected by dual luciferase assay. Isoliquiritigenin inhibited proliferation and induced apoptosis of tongue squamous cell carcinoma cells, and decreased miR-21 levels and promoted forkhead box G1 expression. Forkhead box G1 was then identified as a target of miR-21 and ISL could promote forkhead box G1 expression by inhibiting miR-21. Further analysis suggested that upregulation of miR-21 improved proliferation and suppressed apoptosis of tongue squamous cell carcinoma cells by inhibiting forkhead box G1 expression. Finally, our results revealed that isoliquiritigenin inhibited proliferation and induced apoptosis of tongue squamous cell carcinoma cells by regulating miR-21. Isoliquiritigenin might act as a novel therapeutic treatment for tongue squamous cell carcinoma cells through up-regulation of forkhead box G1 expression via inhibiting miR-21expression.

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