Novel genetic locus at MHC region for esophageal squamous cell carcinoma in Chinese populations

Zhang, Peng; Li, Xinmin; Zhao, Xueke; Song, Xin; Yuan, Ling; Shen, Fangfang; Fan, Zong-Min; Wang, Lidong

doi:10.1371/journal.pone.0177494

Cited by 5 publications

(11 citation statements)

References 26 publications

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“… 1 In Eastern Asian countries including China, esophageal squamous cell carcinoma (ESCC) is the major histologic type of esophageal cancer. 2 Despite advances in the prevention and treatment of esophageal cancer, the prognosis of this malignancy is still poor. It is estimated that the overall 5-year survival rate for ESCC is <40%.…”

Section: Introductionmentioning

confidence: 99%

Ablation of MCM10 using CRISPR/Cas9 restrains the growth and migration of esophageal squamous cell carcinoma cells through inhibition of Akt signaling

Yan

Jia

et al. 2018

OTT

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IntroductionMinichromosome maintenance 10 (MCM10) is deregulated in several malignancies including cervical cancer and urothelial carcinoma. However, the expression and biologic role of MCM10 in esophageal squamous cell carcinoma (ESCC) is still unknown.MethodsIn this study, we performed immunohistochemistry and real-time polymerase chain reaction (PCR) analysis to examine the expression of MCM10 in ESCC and adjacent normal esophageal tissues. The associations of MCM10 expression with clinicopathologic parameters of ESCC were analyzed. Ablation of MCM10 through the CRISPR/Cas9 technology was conducted and its impact on ESCC cell growth and migration was investigated.ResultsThe mRNA and protein expression levels of MCM10 were significantly greater in ESCC than in normal tissues (P<0.001). The expression of MCM10 was significantly associated with age at diagnosis (P=0.033), but not with gender, differentiation grade, invasion status, or tumor–node–metastasis (TNM) stage. Knockout of MCM10 significantly suppressed the proliferation, colony formation, and migration capacity of EC109 ESCC cells, compared to control cells harboring wild-type MCM10. Mechanistically, MCM10 depletion markedly reduced the phosphorylation of Akt. Overexpression of constitutively active Akt significantly restored the aggressive phenotype of MCM10-null EC109 cells.ConclusionIn conclusion, these results suggest that MCM10 acts as an oncogene in ESCC through activation of Akt signaling and represents a promising therapeutic target for this malignancy.

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Section: Introductionmentioning

confidence: 99%

Ablation of MCM10 using CRISPR/Cas9 restrains the growth and migration of esophageal squamous cell carcinoma cells through inhibition of Akt signaling

Yan

Jia

et al. 2018

OTT

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“…Previous studies have indicated that family history, smoking, alcohol consumption, aging, and gender are risk factors for ESCC. [10,31,32] Our results demonstrated that family history ( P = .004) and tumor size ( P = .029) were preferentially associated with HLA-DQA1 expression. The percentage of patients expressing HLA-DQA1 is higher for negative family history than that of positive family history.…”

Section: Discussionmentioning

confidence: 67%

“…Many studies have revealed that MHC has crucial roles in various cancer types by functioning as potential oncogenes or tumor suppressors. [28–30] In our previous studies, [8–10] we found that multiple genetic factors within the MHC region confer risk to ESCC from high-risk area in northern China, but the mechanism of MHC has not been studied. Further functional studies were needed to elucidate the molecular mechanisms about the MHC genes.…”

Section: Discussionmentioning

confidence: 99%

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High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China

Shen

Pan

et al. 2019

Medicine

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Background: Our previous studies demonstrate that the major histocompatibility complex (MHC) is associated with the progression of esophageal squamous cell carcinoma (ESCC). HLA-DQA1, which belongs to the MHC Class II family, may be a potential biomarker in ESCC progression. However, the association between HLA-DQA1 and ESCC in high-incidence area of northern China has not been well characterized. The purpose of this study is to investigate the relationship of HLA-DQA1 expression with the progression and prognosis of ESCC. Methods: We analyzed the expression profiles of HLA-DQA1 in esophageal cancer (EC) samples in the TCGA database and validated HLA-DQA1 expression by immunohistochemistry, western blotting, and quantitative reverse-transcription polymerase chain reaction in matched EC and normal tissues, respectively. The correlation between HLA-DQA1 expression and clinicopathologic characteristics of ESCC was further analyzed. Result: Immunohistochemical analysis indicated that the expression level of HLA-DQA1 in ESCC tissues was significantly higher than the matched normal tissues ( P < .001). HLA-DQA1 mRNA and protein expression were significantly higher in ESCC tissues compared to the matched normal tissues. Patients with family history negative or with tumor sizes >4 cm were associated with higher HLA-DQA1 expression levels. A prognostic significance of HLA-DQA1 was also found by the Log-rank method, in which high expression of HLA-DQA1 was correlated with a shorter overall survival time. The receiver operating characteristic (ROC) curve analysis yielded the area under the ROC curve value of 0.693. Univariate and multivariate analyses also suggest that high expression of HLA-DQA1 is a potential indicator for poor prognosis of ESCC. Conclusions: Our results demonstrate that HLA-DQA1 plays an important role in ESCC progression and may be a biomarker for ESCC diagnosis and prognosis, as well as a potential target for the treatment of patients with ESCC.

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“…Esophageal carcinoma (EC) remains the sixth leading cause of cancer-associated mortality worldwide, with approximately 442,000 new cases and 440,000 mortalities globally in 2014 [1,2]. As the predominant subtype of EC, esophageal squamous cell carcinoma (ESCC) is frequently diagnosed in Eastern Asian countries, including China, where it accounts for 95% of all EC cases [3,4]. A series of risk factors, such as tobacco smoking and consumption of alcohol and salted vegetables, are reported to be associated with the high incidence of ESCC [5].…”

Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed Genes and miRNAs Associated with Esophageal Squamous Cell Carcinoma by Integrated Analysis of Microarray Data

Zhang

Chen

Cheng

et al. 2020

BioMed Research International

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To identify candidate key genes and miRNAs associated with esophageal squamous cell carcinoma (ESCC) development and prognosis, the gene expression profiles and miRNA microarray data including GSE20347, GSE38129, GSE23400, and GSE55856 were downloaded from the Gene Expression Omnibus (GEO) database. Clinical and survival data were retrieved from The Cancer Genome Atlas (TCGA). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of differentially expressed genes (DEGs) was analyzed via DAVID, while the DEG-associated protein-protein interaction network (PPI) was constructed using the STRING database. Additionally, the miRNA target gene regulatory network and miRNA coregulatory network were constructed, using the Cytoscape software. Survival analysis and prognostic model construction were performed via the survival (version 2.42-6) and rbsurv R packages, respectively. The results showed a total of 2575, 2111, and 1205 DEGs, and 226 differentially expressed miRNAs (DEMs) were identified. Pathway enrichment analyses revealed that DEGs were mainly enriched in 36 pathways, such as the proteasome, p53, and beta-alanine metabolism pathways. Furthermore, 448 nodes and 1144 interactions were identified in the PPI network, with MYC having the highest random walk score. In addition, 7 DEMs in the microarray data, including miR-196a, miR-21, miR-205, miR-194, miR-103, miR-223, and miR-375, were found in the regulatory network. Moreover, several reported disease-related miRNAs, including miR-198a, miR-103, miR-223, miR-21, miR-194, and miR-375, were found to have common target genes with other DEMs. Survival analysis revealed that 85 DEMs were related to prognosis, among which hsa-miR-1248, hsa-miR-1291, hsa-miR-421, and hsa-miR-7-5p were used for a prognostic survival model. Taken together, this study revealed the important roles of DEGs and DEMs in ESCC development, as well as DEMs in the prognosis of ESCC. This will provide potential therapeutic targets and prognostic predictors for ESCC.

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Novel genetic locus at MHC region for esophageal squamous cell carcinoma in Chinese populations

Cited by 5 publications

References 26 publications

Ablation of MCM10 using CRISPR/Cas9 restrains the growth and migration of esophageal squamous cell carcinoma cells through inhibition of Akt signaling

Ablation of MCM10 using CRISPR/Cas9 restrains the growth and migration of esophageal squamous cell carcinoma cells through inhibition of Akt signaling

High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China

Identification of Differentially Expressed Genes and miRNAs Associated with Esophageal Squamous Cell Carcinoma by Integrated Analysis of Microarray Data

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