Differential expression profiling of microRNAs and their potential involvement in esophageal squamous cell carcinoma

Abstract Objective: Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorly estimated. Thus, this study aimed to investigate the expressions of key regulators of apoptosis and autophagy in matched paired samples of primary and recurrent ESCC. Methods: The medical records of patients with locally advanced ESCC who developed local recurrence after dCRT were reviewed, and the expression profiling of apoptosis-related genes, cell apoptosis, autophagy and autophagy-related proteins were detected in normal esophageal squamous epithelium and paired samples of primary and recurrent ESCC.Results: A total of 126 patients were enrolled, and 52.4% of them had stage III disease. The 1-, 3- and 5-year local recurrence-free survival (LRFS) rates were 54.8, 19.8 and 14.3%, respectively, with a median LRFS of 13.0 months. Patients with T2 tumor or stage II disease showed a significantly prolonged LRFS compared with that of patients with T3-4 tumor or stage III disease. The Apoptotic Machinery key genes expression profiling identified 5 upregulated and 7 downregulated apoptosis-related genes in recurrent tumors compared with their expression levels in the matched primary ESCC tumors. High expression of CD40, TRAF4 and BCL2A1, and low expression of CARD6 and TNFRSF21 were associated with increased risk of early local recurrence after dCRT. No differences in apoptotic index between primary and recurrent samples were detected. However, typical morphological features of autophagosomes and elevated LC3-II protein expression were detected in recurrent tumor samples, and positive LC3-II expression was correlated with increased risk of early local recurrence.Conclussion: Our findings indicated that apoptosis and autophagy dysfunction correlated with early local recurrence in patients with locally advanced ESCC receiving dCRT. Further studies are necessary to understand the biology of tumor recurrence in esophageal cancer.

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Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations

SSRN Electronic Journal ◽

10.2139/ssrn.3247854 ◽

2018 ◽

Author(s):

Fengling Wang ◽

Zhongyi Yan ◽

Jiajia Lv ◽

Junfang Xin ◽

Yifang Dang ◽

...

Keyword(s):

Gene Expression ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Gene Expression Profiling ◽

Squamous Cell ◽

Expression Profiling ◽

Molecular Subtypes ◽

Asian Populations

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RNA sequencing to highlight the heterogeneity in circulating exosomes from patients with esophageal squamous cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15546 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15546-e15546

Author(s):

Lin Yang ◽

Wenjing Zheng ◽

Zheng Wang ◽

Peikun Ding ◽

Lijuan Ling ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Differential Expression ◽

Rna Sequencing ◽

Squamous Cell ◽

Tumor Heterogeneity ◽

Molecular Heterogeneity ◽

Healthy Controls ◽

Rna Seq

e15546 Background: Dissecting tumor heterogeneity is crucial for understanding tumor prognosis, response to therapy, and metastasis. But current tissue biopsy-based strategies for characterizing molecular heterogeneity are invasive and may be confounded by intra-tumor heterogeneity. Here we explore whether exosomes that contain bioactive molecules from the cell of origin can provide new noninvasive means to delineate the heterogeneity of human cancers. Methods: We used RNA-sequencing (RNA-seq) to perform unbiased profiling of mRNAs and long noncoding RNAs (lncRNAs) in plasma exosomes isolated from patients with esophageal squamous cell carcinoma (ESCC, n = 6), patients with esophagitis (n = 6), and healthy controls (n = 6). Results: The number of expressed genes detected in our data set is 63355, including 29615 lncRNAs. We found that exosomes from ESCC have dramatically distinct transcriptome and lncRNA landscapes from that of esophagitis and healthy controls, with 2278 genes and 584 lncRNAs showing differential expression between ESCC and controls; and 854 genes and 126 lncRNAs displaying differential expression between ESCC and esophagitis. We also observed variable expression of diverse transcriptional patterns related to immune response, signal transduction, cell mobility, and transmembrane protein binding, as well as differentially expressed 953 lncRNAs between Stage I and Stage II ESCC samples. Finally, we discovered that both gene and lncRNA expression profiles are variably across exosomal samples from different ESCC patients. Conclusions: Our data reveals that exosomes from ESCC contain distinct transcriptional and lncRNA profiles that separate ESCC from benign esophagitis and healthy controls. Our analysis also identifies unappreciated molecular heterogeneity in exosomes of ESCC, which may pave the way for using exosomal RNA-seq to decode molecular heterogeneity in cancers.

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