Esophageal carcinoma: Towards targeted therapies

Hassanabad, Ali Fatehi; Chehade, Rania; Breadner, Daniel; Raphael, Jacques

doi:10.1007/s13402-019-00488-2

Cited by 103 publications

(84 citation statements)

References 81 publications

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“…ESCA is considered to be a multifactor, multigene, and multistage complicated disease ( 27 ). Its occurrence is closely related to chronic nitrosamine stimulation, inflammation and trauma, genetic and epigenetic modification, and other factors ( 29 , 32 ). Operation, radiotherapy, and chemotherapy are still the main treatment methods for ESCA, but inoperableness and radiochemotherapy resistance limit the clinical effect ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

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N6-methyladenosine (m 6 A) modification is the most abundant modification on eukaryotic RNA. In recent years, lots of studies have reported that m 6 A modification and m 6 A RNA methylation regulators were involved in cancer progression. However, the m 6 A level and its regulators in esophageal cancer (ESCA) remain poorly understood. In this study, we analyzed the expression of m 6 A regulators using The Cancer Genome Atlas data and found 14 of 19 m 6 A regulators are significantly increased in ESCA samples. Then we performed a univariate Cox regression analysis and LASSO (least absolute shrinkage and selection operator) Cox regression model to investigate the prognostic role of m 6 A regulators in ESCA, and the results indicated that a two-gene prognostic signature including ALKBH5 and HNRNPA2B1 could predict overall survival of ESCA patients. Moreover, HNRNPA2B1 is higher expressed in high-risk scores subtype of ESCA, indicating that HNRNPA2B1 may be involved in ESCA development. Subsequently, we confirmed that the level of m 6 A and HNRNPA2B1 was significantly increased in ESCA. We also found that HNRNPA2B1 expression positively correlated with tumor diameter and lymphatic metastasis of ESCA. Moreover, functional study showed that knockdown of HNRNPA2B1 inhibited the proliferation, migration, and invasion of ESCA. Mechanistically, we found that knockdown of HNRNPA2B1 inhibited the expression of de novo fatty acid synthetic enzymes, ACLY and ACC1, and subsequently suppressed cellular lipid accumulation. In conclusion, our study provides critical clues to understand the role of m 6 A and its regulators in ESCA. Moreover, HNRNPA2B1 functions as an oncogenic factor in promoting ESCA progression via up-regulation of fatty acid synthesis enzymes ACLY and ACC1, and it may be a promising prognostic biomarker and therapeutic target for human ESCA.

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Section: Discussionmentioning

confidence: 99%

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Guo

Wang

et al. 2020

Front. Oncol.

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“…Patients with localized EAC have benefited from surgical and postoperative therapies, including neoadjuvant chemotherapy or chemoradiotherapy [4,5]. However, managements of advanced stage or metastatic EAC only include palliative treatments and supportive care [6,7]. In addition, the high rate of resistance to chemotherapy or radio chemotherapy also contributed to the poor prognosis [2].…”

Section: Introductionmentioning

confidence: 99%

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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“…It is usually diagnosed in the late stage due to the lack of specific initial symptoms. For late-stage EC, the main treatment is surgery combined with chemotherapy [18,19]. However, the cure and survival rates of patients are still very low, and other methods are needed to help predict the survival rate and identify potential responders of a given treatment.…”

Section: Discussionmentioning

confidence: 99%

The correlation and clinical significance of PIK3CA, PIK3CB and HPV infection in esophageal squamous cell carcinoma

Wen¹,

Li²,

He³

et al. 2020

Preprint

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Background: Esophageal squamous cell carcinoma (ESCC) is a highly lethal cancer. Currently, human papillomavirus (HPV) is considered as a potential risk factor for ESCC, but this assumption is still contradictory. PI3K/Akt/mTOR network plays a key role in the virus/host cell crosstalk in HPV positive cancer cells. The purpose of this study was to investigate the relationship between the expression of PIK3CA, PIK3CB and HPV infection.Methods: The expression of PIK3CA, PIK3CB, p16 and p53 in 156 cases of ESCC was detected by immunohistochemistry. Patients are followed up by telephone or clinic.Results: In this study, the positive rates of PIK3CA, PIK3CB, p53 and p16 in ESCC were significantly higher than in normal esophageal mucosa. The expression of PIK3CA and PIK3CB was related to TNM stage and lymph node metastasis. The expression of p53 is related to the depth of tumor invasion.High p16 expression was found to be significantly correlated with tumor location, TNM stage, differentiation grade and lymph node metastasis. P16 expression is positively correlated with PIK3CA expression but not with PIK3CB and p53. Survival analysis further indicated that that PIK3CA and p53 were markers of poor diagnosis. P16 is a mark of favorable prognosis in ESCC. Conclusions: The expression of PIK3CA and PIK3CB is related to the development of ESCC. The imbalance of PI3K/Akt signaling pathway is closely related to HPV infection and prognosis. The combined detection of PIK3CA and p16 is of great significance to evaluate the prognosis and optimize the treatment of ESCC. Background Esophageal cancer (EC) represents the eighth highest incidence of cancer worldwide (456,000 cases/year) and is usually diagnosed at an advanced stage, showing rapid progression and extremely poor prognosis [1, 2]. The two main histological types of EC are squamous cell carcinoma and adenocarcinoma, and 90% of cases are esophageal squamous cell carcinoma (ESCC). Despite advances in medical technology, such as early screening and surgery combined with chemotherapy or radiotherapy, the prognosis of EC is still very poor [3]. Therefore, elucidating the underlying pathogenesis of EC and identifying effective biological agents are urgently needed.

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Esophageal carcinoma: Towards targeted therapies

Cited by 103 publications

References 81 publications

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1

Profiles of autophagy-related genes in esophageal adenocarcinoma

The correlation and clinical significance of PIK3CA, PIK3CB and HPV infection in esophageal squamous cell carcinoma

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