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S100A9 作为一种新型的人类胃癌诊断和预后生物标志物。

S100A9 as a novel diagnostic and prognostic biomarker in human gastric cancer.

机构信息

Department of Surgery, The Sixth Medical Center of PLA General Hospital, Beijing, China.

Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.

出版信息

Scand J Gastroenterol. 2020 Mar;55(3):338-346. doi: 10.1080/00365521.2020.1737883. Epub 2020 Mar 15.

Abstract

The morbidity and mortality of gastric cancer (GC) is high, but there are lack of the biomarkers for early diagnosis and progression of GC. We aimed to identify a novel biomarker for the growth and progression of GC. The Cancer Genome Atlas (TCGA) database including 352 eligible patients was used to screen candidate genes related to the prognosis of GC. A proteomics analysis of Chinese Human Proteome Sketches (CHPS) including 84 eligible sample tissues was conducted to further identify candidate biomarkers. A series of assays were performed to investigate the functions of candidate proteins in GC. Next, to verify whether the candidate oncogene was associated with gastric carcinogenesis, we screened its expression levels using samples from 200 patients with chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia, or GC and healthy controls. According to the analyses of the TCGA database and CHPS, we found that S100A9 may be associated with the prognosis of GC. The results of proliferation, wound-healing and invasion assays, immunohistochemistry (IHC) and western blot showed that high levels of S100A9 in tissues were significantly associated with GC aggressiveness and a poor prognosis ( < .05). Furthermore, we found that the expression of S100A9 increased gradually during the process of gastric carcinogenesis ( < .05). The diagnostic sensitivity and specificity of S100A9 as a biomarker for early GC were 61.4% and 81.3%, respectively. This study reveals that S100A9 may be a novel biomarker for the early diagnosis and prognosis of GC patients.

摘要

胃癌(GC)的发病率和死亡率较高,但缺乏用于 GC 早期诊断和进展的生物标志物。我们旨在鉴定用于 GC 生长和进展的新型生物标志物。使用包括 352 名合格患者的癌症基因组图谱(TCGA)数据库筛选与 GC 预后相关的候选基因。对包括 84 个合格样本组织的中国人类蛋白质图谱草图(CHPS)进行蛋白质组学分析,以进一步鉴定候选生物标志物。进行了一系列测定以研究候选蛋白在 GC 中的功能。接下来,为了验证候选癌基因是否与胃癌发生有关,我们使用来自 200 名慢性萎缩性胃炎(CAG)、肠上皮化生(IM)、发育不良或 GC 患者和健康对照的样本筛选其表达水平。根据 TCGA 数据库和 CHPS 的分析,我们发现 S100A9 可能与 GC 的预后有关。增殖、划痕愈合和侵袭测定、免疫组织化学(IHC)和 Western blot 的结果表明,组织中高水平的 S100A9 与 GC 的侵袭性和不良预后显着相关( < .05)。此外,我们发现 S100A9 的表达在胃癌发生过程中逐渐增加( < .05)。S100A9 作为早期 GC 生物标志物的诊断灵敏度和特异性分别为 61.4%和 81.3%。这项研究表明 S100A9 可能是 GC 患者早期诊断和预后的新型生物标志物。

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