当前位置： SCI文献检索 > CANCER期刊下所有文献 > Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications.

Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications.

Abstract：

BACKGROUND:Recent preclinical explorations strongly support the tumorigenic potential of bile on laryngopharyngeal mucosa. Herein, the authors describe, in bile-related human hypopharyngeal squamous cell carcinoma (HSCC), NF-κB-related messenger RNA (mRNA) and microRNA (miRNA) oncogenic phenotypes similar to those previously identified in acidic bile-exposed premalignant murine hypopharyngeal mucosa. METHODS:In this pilot study, the authors included human HSCC specimens paired with their adjacent normal tissue (ANT) derived from 3 representative patients with documented biliary laryngopharyngeal reflux (bile[+]) compared with 5 control patients without signs of bile reflux disease (bile[-]). Immunohistochemical, quantitative polymerase chain reaction, and miRNA analyses were used to detect the levels of activated NF-κB and expression levels of STAT3, EGFR, BCL2, WNT5A, IL-6, IL-1B, ΔNp63, cREL, TNF-α, TP53, NOTCH1, NOTCH2, NOTCH3, miR-21, miR-155, miR-192, miR-34a, miR-375, miR-451a, miR-489, miR-504, and miR-99a. RESULTS:Bile(+) HSCC demonstrated an intense NF-κB activation accompanied by significant overexpression of RELA(p65), EGFR, STAT3, BCL-2, cREL, ΔNp63, WNT5A, IL-6, and IL1B; upregulation of oncomir miR-21; and downregulation of tumor suppressor miR-375 compared with their respective ANTs. Bile(+) HSCC demonstrated significantly higher mRNA levels of all the analyzed genes, particularly RELA(p65), IL-6, EGFR, and TNF-α compared with bile(-) tumors. The miR-21/miR-375 ratio, which previously has been linked to tumor aggressiveness, was found to be >260-fold and >30-fold higher, respectively, in bile(+) HSCCs compared with their ANTs and bile(-) tumors. CONCLUSIONS:Although limitations apply to this pilot study due to the small number of patients with HSCC, the novel findings suggest that a history of bile as a component of esophageal reflux disease may represent an independent risk factor for hypopharyngeal carcinogenesis.

journal_name

Cancer

journal_title

Cancer

authors

Sasaki CT,Doukas SG,Costa J,Vageli DP

doi

10.1002/cncr.32369

subject

Has Abstract

pub_date

2019-10-15 00:00:00

pages

3554-3565

issue

eissn

0008-543X

issn

1097-0142

journal_volume

125

pub_type

杂志文章

在线工具

Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications.