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定植与阳性胃癌患者的生存降低有关。

colonization is associated with decreased survival of -positive gastric cancer patients.

机构信息

Department of Gastroenterology and Hepatology, Chiayi Chang Gung Memorial Hospital, Chiayi 61301, Taiwan.

Department of Applied Mathematics, National Chiayi University, Chiayi 60035, Taiwan.

出版信息

World J Gastroenterol. 2021 Nov 14;27(42):7311-7323. doi: 10.3748/wjg.v27.i42.7311.

Abstract

BACKGROUND

An increased amount of () is frequently detected in the gastric cancer-associated microbiota of the Taiwanese population. is known to exert cytotoxic effects and play a role in the progression of colorectal cancer, though the impact of colonization on gastric cancer cells and patient prognosis has not yet been examined.

AIM

To identify dependent molecular pathways in gastric cancer cells and to determine the impact of on survival in gastric cancer.

METHODS

Coculture of with a gastric cancer cell line was performed, and changes in gene expression were investigated. Genes with significant changes in expression were identified by RNA sequencing. Pathway analysis was carried out to determine deregulated cellular functions. A cohort of gastric cancer patients undergoing gastrectomy was recruited, and nested polymerase chain reaction was performed to detect the presence of in resected cancer tissues. Statistical analysis was performed to determine whether colonization affects patient survival.

RESULTS

RNA sequencing and subsequent pathway analysis revealed a drastic interferon response induced by a high colonization load. This response peaked within 24 h and subsided after 72 h of incubation. In contrast, deregulation of actin and its regulators was observed during prolonged incubation under a low colonization load, likely altering the mobility of gastric cancer cells. According to the clinical specimen analysis, approximately one-third of the gastric cancer patients were positive for , and statistical analysis indicated that the risk for colonization increases in late-stage cancer patients. Survival analysis demonstrated that colonization was associated with poorer outcomes among patients also positive for ().

CONCLUSION

colonization leads to deregulation of actin dynamics and likely changes cancer cell mobility. Cohort analysis demonstrated that colonization leads to poorer prognosis in positive patients with late-stage gastric cancer. Hence, combined colonization of and is a predictive biomarker for poorer survival in late-stage gastric cancer patients treated with gastrectomy.

摘要

背景

在台湾人群的胃癌相关微生物群中,经常检测到()的含量增加。已知()具有细胞毒性作用,并在结直肠癌的进展中发挥作用,尽管()定植对胃癌细胞和患者预后的影响尚未得到检验。

目的

鉴定胃癌细胞中依赖的分子途径,并确定()对胃癌患者生存的影响。

方法

进行()与胃癌细胞系的共培养,并研究基因表达的变化。通过 RNA 测序鉴定表达有显著变化的基因。进行通路分析以确定失调的细胞功能。招募接受胃切除术的胃癌患者队列,并进行嵌套聚合酶链反应以检测切除的癌症组织中()的存在。进行统计分析以确定()定植是否影响患者生存。

结果

RNA 测序和随后的通路分析显示,高定植负荷强烈诱导干扰素反应。这种反应在孵育 24 小时内达到峰值,并在 72 小时后消退。相比之下,在低定植负荷下长时间孵育时观察到肌动蛋白及其调节剂的失调,可能改变胃癌细胞的迁移能力。根据临床标本分析,大约三分之一的胃癌患者()呈阳性,统计分析表明,晚期癌症患者的定植风险增加。生存分析表明,()定植与同时()阳性的患者预后较差相关()。

结论

()定植导致肌动蛋白动态的失调,并可能改变癌细胞的迁移能力。队列分析表明,()和()的定植导致接受胃切除术治疗的晚期胃癌患者预后较差。因此,()和()的联合定植是接受胃切除术治疗的晚期胃癌患者生存较差的预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a9b/8611209/e93be7b42028/WJG-27-7311-g001.jpg

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