Table_1_RNA Sequencing Revealed Signals of Evolution From Gallbladder Stone to Gallbladder Carcinoma.XLSX

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. ALPP and GPR87 are potential biomarkers for predicting cancer risk in patients with gallstones. The in vitro results 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.

胆囊结石是胆囊癌（gallbladder carcinoma, GBC）的主要危险因素，但目前针对确诊无症状胆囊结石后的随访时长是否会增加胆囊癌发病风险这一问题仍存在争议。本研究纳入我院收治的10例胆囊癌患者与30例胆囊结石患者。根据随访时长将胆囊结石患者分为3组：随访周期1~3年者为GS3组（10例）、随访周期5~10年者为GS5组（10例）、随访周期超过10年者为GS10组（10例）。采集胆囊癌患者的肿瘤及癌旁组织，以及胆囊结石患者的胆囊组织，对上述50例样本开展RNA测序。此外，相较于10例胆囊癌患者的癌旁组织，肿瘤组织中共鉴定出1704个差异表达基因（differentially expressed genes, DEGs），这些基因富集于多条经典癌症相关通路，包括PI3K-Akt、丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）、Ras及Wnt信号通路，其中富集程度最显著的通路为神经活性配体-受体相互作用通路。随访时长为1~3年与超过10年的胆囊结石患者，其癌症发病风险高于随访时长为5~10年的患者。ALPP与GPR87可作为预测胆囊结石患者癌症发病风险的潜在生物标志物。体外实验结果显示，GPR87能够促进胆囊癌细胞的增殖、迁移与侵袭。本研究从转录组层面探讨了胆囊癌患者与不同随访时长的胆囊结石患者之间的关联。