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胃癌风险增加人群胃生态位中的差异可塑性

Differential Plasticity in the Gastric Niche of Subjects at Increased Gastric Cancer Risk.

作者信息

Casarotto Mariateresa, Pratesi Chiara, Bidoli Ettore, Maiero Stefania, Magris Raffaella, Steffan Agostino, Basaglia Giancarlo, Canzonieri Vincenzo, De Re Valli, Cannizzaro Renato, Zanussi Stefania

机构信息

Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.

Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, 33081 Aviano, Italy.

出版信息

Pathogens. 2019 May 18;8(2):65. doi: 10.3390/pathogens8020065.

Abstract

() represents an independent risk factor for Gastric Cancer (GC). First Degree Relatives (FDR) of GC subjects and Autoimmune Gastritis (AG) patients are both at increased risk for GC. genetic heterogeneity within the gastric niche of FDR and AG individuals has been little explored. To understand whether they exploit an increased stability and virulence, 14 AG, 25 FDR, 39 GC and 13 dyspeptic patients (D) were investigated by a cultural PCR-based approach characterizing single colonies-forming-units. We chose three loci within the Cytotoxin-associated gene-A Pathogenicity Island (CagPAI) (,,), and as markers of virulence with reported association to GC. Inflammatory/precancerous lesions were staged according to Sydney System. When compared to D, FDR, similarly to GC patients, were associated to higher atrophy (OR = 6.29; 95% CI:1.23-31.96 in FDR; OR = 7.50; 95% CI:1.67-33.72 in GC) and a lower frequency of mixed infections (OR = 0.16; 95% CI:0.03-0.81 in FDR; OR = 0.10; 95% CI:0.02-0.48 in GC). FDR presented also an increased neutrophil infiltration (OR = 7.19; 95% CI:1.16-44.65). Both FDR and GC carried a higher proportion of CagPAI profiles (OR = 2.71; 95% CI: 1.66-4.41 and OR = 3.43; 95% CI: 2.16-5.44, respectively). Conversely, AG patients presented a lower frequency of subtypes carrying a stable CagPAI and . These results underline different plasticity in FDR and AG individuals, and thus, a different host-bacterium interaction capacity that should be considered in the context of eradication therapies.

摘要

()是胃癌(GC)的一个独立危险因素。GC患者的一级亲属(FDR)和自身免疫性胃炎(AG)患者患GC的风险均增加。FDR和AG个体胃生态位内的基因异质性鲜有研究。为了解它们是否利用了增强的稳定性和毒力,采用基于培养PCR的方法对14例AG患者、25例FDR、39例GC患者和13例消化不良患者(D)进行了研究,该方法可对单菌落形成单位进行特征分析。我们选择了细胞毒素相关基因A致病岛(CagPAI)内的三个位点(、、),并将其作为与GC相关的毒力标记。炎症/癌前病变根据悉尼系统进行分期。与D组相比,FDR组与GC患者相似,萎缩程度更高(FDR组的OR = 6.29;95% CI:1.23 - 31.96;GC组的OR = 7.50;95% CI:1.67 - 33.72),混合感染频率更低(FDR组的OR = 0.16;95% CI:0.03 - 0.81;GC组的OR = 0.10;95% CI:0.02 - 0.48)。FDR组的中性粒细胞浸润也增加(OR = 7.19;95% CI:1.16 - 44.65)。FDR组和GC组携带CagPAI谱的比例均更高(分别为OR = 2.71;95% CI:1.66 - 4.41和OR = 3.43;95% CI:2.16 - 5.XX,此处原文95% CI下限疑似有误,应为2.16 - 5.44)。相反,AG患者携带稳定CagPAI和的亚型频率较低。这些结果强调了FDR组和AG个体存在不同的可塑性,因此,在根除治疗的背景下应考虑不同的宿主 - 细菌相互作用能力。 (注:原文中95% CI:2.16 - 5.XX处XX疑似有误,根据语境推测应为5.44)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19eb/6630233/d2014243a6d8/pathogens-08-00065-g001.jpg

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