Human Microbiota in Esophageal Adenocarcinoma: Pathogenesis, Diagnosis, Prognosis and Therapeutic Implications

Esophageal adenocarcinoma (EAC) is one of the main subtypes of esophageal cancer. The incidence rate of EAC increased progressively while the 5-year relative survival rates were poor in the past two decades. The mechanism of EAC has been studied extensively in relation to genetic factors, but less so with respect to human microbiota. Currently, researches about the relationship between EAC and the human microbiota is a newly emerging field of study. Herein, we present the current state of knowledge linking human microbiota to esophageal adenocarcinoma and its precursor lesion—gastroesophageal reflux disease and Barrett’s esophagus. There are specific human bacterial alternations in the process of esophageal carcinogenesis. And bacterial dysbiosis plays an important role in the process of esophageal carcinogenesis via inflammation, microbial metabolism and genotoxicity. Based on the human microbiota alternation in the EAC cascade, it provides potential microbiome-based clinical application. This review is focused on novel targets in prevention, diagnosis, prognosis, and therapy for esophageal adenocarcinoma.

CD147 expression lacks prognostic relevance in esophageal cancer

Introduction The role of CD147 as an important indicator of tumor prognosis remains controversially discussed in literature. We focused on the prognostic significance of CD147 expression in esophageal cancer patients. While some studies report that CD147 is an unfavorable prognostic factor in esophageal squamous cell carcinoma, others showed no significant correlation. However, only one study draws attention to the significance of CD147 in esophageal adenocarcinoma, which is one of the most rapidly increasing neoplasms in the western world. Methods To finally clarify the impact of CD147 as a prognostic factor, especially for esophageal adenocarcinomas, we analyzed CD147 expression in a tissue microarray of 359 esophageal adenocarcinomas and 254 esophageal squamous cell cancer specimens. For the immuno-histochemical analysis, we used a primary antibody specific for CD147. Staining intensity and proportion of positive tumor cells were scored (negative, weak, moderate, strong staining). These findings were compared to normal esophageal tissue and correlated to the histopathological tumor phenotype and survival data. Results CD147 expression was detectable in weak intensities in benign esophageal tissue (85.78%) and expressed in predominately moderate to strong intensities in esophageal cancer (88.34%). Strong CD147 immunostaining was linked to increased infiltration depth (p = 0.015) and differentiation (p = 0.016) in esophageal squamous cell cancer but revealed no significant correlation with histopathology of adenocarcinoma. Moreover, CD147 intensity was unrelated to overall survival in this collective for both subtypes of esophageal cancer. Conclusion Thus, our data show that CD147 has no prognostic value, neither in esophageal adenocarcinoma nor squamous cell carcinoma.

Reflux, Barrett’s Esophagus, and Esophageal Adenocarcinoma After Bariatric Surgery

We present the case of a patient who developed esophageal adenocarcinoma after a previous laparoscopic sleeve gastrectomy. Bariatric surgery has emerged as the most effective treatment option for weight loss and obesity-related diseases; however, sleeve gastrectomy promotes gastroesophageal reflux and leads to Barrett’s esophagus in a substantial portion of patients. The natural history of Barrett’s esophagus in these patients is unknown, and active surveillance is recommended until the incidence of dysplasia and adenocarcinoma in this population is clarified. Management options for these patients include conversion to Roux-en-Y gastric bypass. Although esophagectomy in patients who have previously undergone sleeve gastrectomy may require an alternative conduit, the remnant stomach can be used in carefully selected patients. Here, we review the different weight loss procedures, their effect on gastroesophageal reflux disease and Barrett’s esophagus, and the treatment options for patients with esophageal cancer after sleeve gastrectomy. We report the use of preoperative coil embolization as a means of vascular preconditioning before successful use of a gastric conduit.

Identification of the Potential Biomarkers in Barrett’S Esophagus Derived Esophageal Adenocarcinoma

Clinically, almost 50% of esophageal adenocarcinoma (EAC) originates from the progression of Barrett’s esophagus (BE). EAC is often diagnosed at late stages and is related to dismal prognosis. However, there are still no effective strategies for stratification and therapy in BE derived EAC (BE-EAC). Two public datasets (GSE26886 and GSE37200) are analyzed to identify differentially expressed genes (DEGs) between BE and EAC. A series of bioinformatics analyses are performed to explore potential biomarkers associated with BE-EAC. 27 up- and 104 down-regulated genes are identified between GSE26886 and GSE37200. The GO and KEGG enrichment analysis indicate that the DEGs are highly involved in tumorigenesis. Subsequently, Weighted Gene Co-Expression Network Analysis (WGCNA) is performed to explore the potential genes related to BE-EAC, which are further validated in The Cancer Genome Atlas (TCGA) database. 5 up-regulated genes (MYO1A, ACE2, COL1A1, LGALS4, and ADRA2A) and 3 down-regulated genes (AADAC, RAB27A, and P2RY14) were found in BE-EAC. Among them, the expression level of AADAC, ACE2 and ADRA2A show a significant correlation with patients’ survival probability. In conclusion, MYO1A, ACE2, COL1A1, LGALS4, ADRA2A, AADAC, RAB27A, and P2RY14 are potential diagnostic and prognostic biomarkers in BE-EAC.