关键词: 乙醇脱氢酶1A, 肺腺癌, 细胞功能实验, 生存分析

Abstract:

Objective To investigate the effect of the expression of alcohol dehydrogenase 1A（ADH-1A） protein on the biological behavior of lung adenocarcinoma（LUAD） cells and the correlation with the pathological characteristics and prognosis of LUAD patients. Methods A total of 172 LUAD patients from Taizhou Municipal Hospital from January 2013 to December 2017 were enrolled. The clinical data，as well as cancer tissues and adjacent tissues，were collected，and the expression of ADH-1A was determined. The patients were classified into negative group（111 cases） with <5% ADH-1A positive cells and positive group（61 cases） with ≥5% ADH-1A positive cells. All the patients were followed up for 24 months，and the overall survival time and progression-free survival time（PFS） of the patients were recorded. The differentially expressed genes of LUAD patients were screened through the GEO database and Starbase database，and the expression of ADH-1A in LUAD tissues and its relationship with the survival period of LUAD patients were analyzed. The ADH-1A overexpression plasmid was transfected into A549 cells，and the oe-ADH-1A group（transfected with ADH-1A overexpression plasmid） and oe-NC group（transfected with empty plasmid） were classified according to the different transfection plasmids. The effects of ADH-1A overexpression on the proliferation，migration and invasion ability of A549 cells were analyzed by CCK-8 test，cell proliferation test and scratch test. The survival situation of LUAD patients was evaluated by Kaplan-Meier survival curve. The factors influencing the shortened overall survival period of LUAD patients were analyzed by Cox regression. Results The ADH-1A expression in the cancer tissues of LUAD patients was low（P<0.000 1）.The overall survival time of LUAD patients with high ADH-1A expression was longer than that of those with low expression（P=0.004 7）. The positive rate of ADH-1A protein in the cancer tissues of LUAD patients was lower than that in the adjacent tissues（P<0.000 1）. The total survival time and progression-free survival（PFS） of ADH-1A positive group were longer than those of ADH-1A negative group（P<0.01）. Overexpression of ADH-1A could inhibit the proliferation，migration and invasion ability of A549 cells（P<0.000 1）. Gender being female and ADH-1A being negative were risk factors for the shortened overall survival period of LUAD patients [hazard ratios（HR） were 1.686 and 0.501，95% confidence intervals（CI） were 1.112-2.555 and 0.328-0.764，P<0.05]. Conclusions ADH-1A is lowly expressed in the cancer tissues of LUAD patients. Upregulation of its expression can inhibit the proliferation and invasion ability of LUAD cells，or it may serve as a potential prognostic marker and therapeutic target for LUAD.

Key words: Alcohol dehydrogenase 1A, Lung adenocarcinoma, Cell function experiment, Survival analysis