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Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma.

ABSTRACT: Patients with inactive acetaldehyde dehydrogenase 2 (ALDH2) are at high risk for esophageal squamous cell carcinoma (ESCC) and hypopharyngeal squamous cell carcinoma (HPSCC). The acetaldehyde breath test (ABT) may demonstrate ALDH2 gene polymorphisms. We evaluated the usefulness of the ABT in patients with ESCC and HPSCC. The squamous cell carcinoma (SCC) group consisted of 100 patients who were treated with endoscopic submucosal dissection (ESD) for ESCC or HPSCC, and the control group (HC) consisted of 275 healthy subjects. The SCC group comprised the "single subgroup" (n = 63), in which a single lesion was initially treated with ESD, and the "multiple subgroup" (n = 31), in which multiple lesions were initially treated with ESD. First, we compared the groups' risk factors for carcinogenesis and measured the acetaldehyde-to-ethanol (A/E) ratio. Then we tested the groups' differences in the abovementioned carcinogenic risk factors. We found that the proportion of individuals in the SCC group with inactive ALDH2 (A/E ratio ≥ 23.3) was significantly higher than that in the HC group (p = 0.035), as was the A/E ratio (p < 0.001). Also, the proportion of individuals with inactive ALDH2 in the multiple subgroup was significantly higher than that in single subgroup (p = 0.015), as was the A/E ratio (p = 0.008). In conclusion, ABT may be a potential screening tool for detecting people at risk of ESCC and HPSCC. In addition, it could be a useful tool in detecting patients at risk of multiple or double carcinomas among patients with ESCC and HPSCC. Trial registration: Trial Registration number: UMIN000040615 [https://rctportal.niph.go.jp/en/detail?trial_id=UMIN000040615], Data of Registration: 01 46 June 2020, retrospectively registered.

SUBMITTER: Sasaki F

PROVIDER: S-EPMC8133406 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:We attempted to identify novel biomarkers and therapeutic targets for esophageal squamous cell carcinoma by gene expression profiling of frozen esophageal squamous carcinoma specimens and examined the functional relevance of a newly discovered marker gene, WDR66. METHODS:Laser capture microdissection technique was applied to collect the cells from well-defined tumor areas in collaboration with an experienced pathologist. Whole human gene expression profiling of frozen esophageal squamous carcinoma specimens (n = 10) and normal esophageal squamous tissue (n = 18) was performed using microarray technology. A gene encoding WDR66, WD repeat-containing protein 66 was significantly highly expressed in esophageal squamous carcinoma specimens. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in a second and independent cohort (n = 71) consisting of esophageal squamous cell carcinoma (n = 25), normal esophagus (n = 11), esophageal adenocarcinoma (n = 13), gastric adenocarcinoma (n = 15) and colorectal cancers (n = 7). In order to understand WDR66's functional relevance siRNA-mediated knockdown was performed in a human esophageal squamous cell carcinoma cell line, KYSE520 and the effects of this treatment were then checked by another microarray analysis. RESULTS:High WDR66 expression was significantly associated with poor overall survival (P = 0.031) of patients suffering from esophageal squamous carcinomas. Multivariate Cox regression analysis revealed that WDR66 expression remained an independent prognostic factor (P = 0.042). WDR66 knockdown by RNA interference resulted particularly in changes of the expression of membrane components. Expression of vimentin was down regulated in WDR66 knockdown cells while that of the tight junction protein occludin was markedly up regulated. Furthermore, siRNA-mediated knockdown of WDR66 resulted in suppression of cell growth and reduced cell motility. CONCLUSIONS:WDR66 might be a useful biomarker for risk stratification of esophageal squamous carcinomas. WDR66 expression is likely to play an important role in esophageal squamous cell carcinoma growth and invasion as a positive modulator of epithelial-mesenchymal transition. Furthermore, due to its high expression and possible functional relevance, WDR66 might be a novel drug target for the treatment of squamous carcinoma.

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Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma.

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