Genetic polymorphisms of ATG5 predict survival and recurrence in patients with early-stage esophageal squamous cell carcinoma

Yang, Pei-Wen; Hsieh, Min‐Shu; Chang, Yu-Ting; Huang, Pei-Ming; Lee, Jang-Ming

doi:10.18632/oncotarget.20793

Cited by 16 publications

(22 citation statements)

References 47 publications

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“…The utility of genes as biomarker has been demonstrated and a number of genes have been reported. In a work by Yang PW et al, increased ATG5 expression was observed in esophageal cancer compared with normal tissue [39]. His group also found higher ATG5 expression tumor group had worse prognosis including the overall survival (OS) and progression-free survival (PFS).…”

Section: Discussionmentioning

confidence: 95%

Profiles of autophagy-related genes in esophageal adenocarcinoma

et al. 2020

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Background Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients. Methods Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. In addition, significantly different ARGs were verified in EAC specimens and normal esophageal mucosal tissues. Results Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR = 0.321, P = 0.046), DAPK1 (HR = 0.636, P = 0.025) and CAPN1 (HR = 0.395, P = 0.004) played protective roles in survival. Gender (HR = 0.225, P = 0.032), stage (HR = 5.841, P = 0.008) and risk score (HR = 1.131, P < 0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P < 0.05). The experimental results confirmed the BIRC5 was overexpressed and the ITPR1, PRKN were downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P < 0.05). Conclusion Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.

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Section: Discussionmentioning

confidence: 95%

Profiles of autophagy-related genes in esophageal adenocarcinoma

et al. 2020

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“…The results showed that esophageal cancer patients with lower expression of ATG5 had a longer overall survival (Figure 5F). Autophagy-related gene 5 (ATG5) is identified as an essential autophagy gene, contributing to the malignant phenotype of cancer cells, and its higher expression is closely associated with poor prognosis in patients with earlystage ESCC (6)(7)(8). However, the association between ATG5 and CDKL3 in cancer has not been studied previously.…”

Section: Gene Expression Profile Analysis Revealed Atg5 Was a Downstrmentioning

confidence: 99%

“…Autophagy is a cellular self-protection process by which it escapes from external stress via metabolizing intracellular proteins and organelles and serves an essential role in carcinogenesis and progression (4,5). ATG5 is identified as a critical autophagy gene, contributing to the malignant feature of cancer cells, and its higher expression predicts poor prognosis in patients with early-stage ESCC (6)(7)(8). However, the association between ATG5 and CDKL3 in cancer has not been studied previously.…”

Section: Introductionmentioning

confidence: 99%

CDKL3 Targets ATG5 to Promote Carcinogenesis of Esophageal Squamous Cell Carcinoma

et al. 2020

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Objective: Our previous study suggested cyclin-dependent kinase-like 3 (CDKL3) acts as a new oncogene in esophageal squamous cell carcinoma (ESCC) cell line TE-1. However, the molecular mechanisms and biological effects of CDKL3 in ESCC remain unknown. In the present study, we aimed to explore the clinical significance of CDKL3 in ESCC and how CDKL3 regulates the malignant behavior of ESCC. Methods: ESCC samples were stained by immunohistochemical staining (IHC) and analyzed for the expression of CDKL3. The functions of CDKL3 on proliferation, apoptosis, migration, invasion, and colony formation were investigated by celigo assay, MTT assay, colony formation, caspase 3/7 activity analysis, transwell migration and invasion assay, respectively. A transplanted tumor model was established to study the functions of FLVCR1 on the tumorigenesis of ESCC cells. Microarray analysis was utilized to identify the CDKL3-regulated genes in ESCC cells. Results: ESCC tumor tissues possessed a significantly higher expression of CDKL3 and autophagy-related gene 5 (ATG5) than matched adjacent normal tissues. The high expressions of CDKL3 were positively associated with the tumor-node-metastasis (TNM) stage and Ki67. Upregulated ATG5 expression was positively correlated with male, advanced tumor (T) stage, and TNM stage. Kaplan-Meier analysis showed that ESCC patients with higher expression of CDKL3 or ATG5 had a shorter overall survival. The worst prognosis was recognized in patients with both high manifestations of CDKL3 and ATG5. Time-dependent receiver operating characteristic (ROC) curve was established to reveal that the combination of CDKL3, ATG5, and TNM stage-based model had better prognostic accuracy than TNM stage. Moreover, CDKL3 knockdown markedly repressed cell growth and aggressivity in vitro and in vivo. Mechanistically, ATG5 was confirmed as a downstream gene involved in the pro-oncogenic function of CDKL3. Conclusion: CDKL3 can be utilized as an independent poor prognostic marker in ESCC patients. Furthermore, CDKL3 may promote tumor profession, invasion, metastasis, and prohibit tumor apoptosis partly by ATG5 activation.

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“…The utility of genes as biomarker has been demonstrated and a number of genes have been reported. In a work by Yang PW et al [38] , increased ATG5 expression was observed in esophageal cancer compared with normal tissue. His group also found higher ATG5 expression tumor group had poorer prognosis including the overall survival (OS) and progression-free survival (PFS).…”

Section: Discussionmentioning

confidence: 95%

Profiles of autophagy-related genes in esophageal adenocarcinoma

Zhu

Dong

Yang

et al. 2020

Preprint

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Background: Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients. Methods: Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. Results: Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR=0.321, P=0.046), DAPK1 (HR=0.636, P=0.025) and CAPN1 (HR=0.395, P=0.004) played protective roles in survival. Gender (HR=0.225, P=0.032), stage (HR=5.841, P=0.008) and risk score (HR=1.131, P＜0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P ＜0.05). Conclusion: Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.

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Genetic polymorphisms of ATG5 predict survival and recurrence in patients with early-stage esophageal squamous cell carcinoma

Cited by 16 publications

References 47 publications

Profiles of autophagy-related genes in esophageal adenocarcinoma

Profiles of autophagy-related genes in esophageal adenocarcinoma

CDKL3 Targets ATG5 to Promote Carcinogenesis of Esophageal Squamous Cell Carcinoma

Profiles of autophagy-related genes in esophageal adenocarcinoma

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