RNA Sequencing Revealed Signals of Evolution From Gallbladder Stone to Gallbladder Carcinoma
RNA Sequencing Revealed Signals of Evolution From Gallbladder Stone to Gallbladder Carcinoma
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DOI：
10.3389/fonc.2020.00823
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发表时间：
2020-05-29
影响因子：
4.7
通讯作者：
Jiang, Xiaoqing
中科院分区：
文献类型：
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作者：
Wang, Jinghan;Xu, Chang;Jiang, Xiaoqing
胆囊结石是胆囊癌（GBC）的主要危险因素，但无症状性胆囊结石的随访时间是否增加GBC的危险性仍存在争议。本研究共收治胆囊癌患者10例，胆囊结石患者30例。根据随访时间将胆囊结石患者分为3组，其中随访1-3年的患者10例（GS 3组），随访5-10年的患者10例（GS 5组），随访10年以上的患者10例（GS 10组）。收集胆囊癌患者的肿瘤和癌旁组织，以及胆囊结石患者的胆囊组织。对50个样品进行RNA测序。此外，在10例GBC患者的肿瘤组织和癌旁组织中共发现1,704个差异表达基因（DEG），这些差异表达基因主要集中在PI 3 K-Akt、丝裂原活化蛋白激酶（MAPK）、Ras和Wnt等已知的肿瘤相关信号通路中，其中最重要的通路是神经活性配体-受体相互作用。随访1-3年和> 10年的胆囊结石患者患癌风险高于随访5-10年的患者，ALP和GPR 87是预测胆囊结石患者患癌风险的潜在生物标志物。体外实验结果表明，GPR-87能促进GBC细胞的增殖、迁移和侵袭。在此，我们探讨了GBC患者和不同随访时间的胆囊结石患者在转录组水平上的关系。
Gallbladder stone is a major risk factor for gallbladder carcinoma (GBC), while there is still a controversy whether period of follow-up since newly diagnoses of asymptomatic gallstones increases the risk of GBC. In this study, 10 GBC patients and 30 patients with gallstones were admitted to our hospital. Patients with gallstones were divided into 3 groups according to the follow-up time, involving 10 patients with follow-up period of 1-3 years (GS3 group), 10 patients with follow-up period of 5-10 years (GS5 group), and 10 patients with follow-up period of more than 10 years (GS10 group). Tumor and para-tumor tissues of GBC patients, and gallbladder tissues of gallstone patients were collected. RNA sequencing was performed on the 50 samples. Besides, 1,704 differentially expressed genes (DEGs) were identified in tumors compared with para-tumor tissues of 10 GBC patients, which were enriched into some well-known cancer-related pathways, such as PI3K-Akt, mitogen-activated protein kinase (MAPK), Ras, and Wnt signaling pathways, and the most significant pathway was neuroactive ligand-receptor interaction. Patients with gallstones with periods of follow-up equal to 1-3 and > 10 years showed to have higher cancer risk than those with 5-10 years.ALPPandGPR87are potential biomarkers for predicting cancer risk in patients with gallstones. Thein vitroresults revealed that GPR-87 can promote the proliferation, migration, and invasion of GBC cells. Herein, we explored the relationship between GBC patients and patients with gallstones with different periods of follow-up in transcriptome level.