胆石病（GS）是胆囊癌（GBC）的重要危险因素。然而，GS 进展为 GBC 的机制仍不清楚。长链非编码RNA（lncRNA）在表观遗传、转录前、转录和转录后水平上调节DNA/RNA/蛋白质，在多种疾病中发挥潜在的治疗作用。本研究旨在鉴定对 GS 促进的 GBC 进展具有潜在影响的 lncRNA。我们医院收治了 6 名无 GS 的 GBC 患者、6 名正常胆囊组织、9 名胆结石和 9 名有 GS 的 GBC 患者。进行下一代 RNA 测序来分析四组差异表达 (DE) lncRNA 和信使 RNA (mRNA)。然后分析重叠和特定的分子特征。我们鉴定了 29 个与胆结石或 GBC 相关的 co-DEG 和 500 个 co-DElncRNA。 co-DEGs和co-DElncRNA的交叉和串联在功能上参与粘着斑、癌症中的转录失调、蛋白质消化和吸收以及ECM-受体相互作用信号通路可能有助于胆囊癌的发展。 GBC 的早期诊断和潜在治疗方法需要进一步探索。 FXYD2、MPZL1 和 PAH 在 co-DEG 和 co-DElncRNA 中均被观察到，并通过 qRT-PCR 进行验证。我们的数据鉴定了一系列参与 GBC 和 GS 相关代谢途径进展的 DEG 和 DElncRNA。与GBC相比，GS图谱在转录组水平上与肿瘤旁组织更相似，并且患癌症的风险更低。有必要对不同时期胆结石随访的 GBC 患者进行进一步探索。© 2024 Wang et al.

Gallstone disease (GS) is an important risk factor for Gallbladder cancer (GBC). However, the mechanisms of the progression of GS to GBC remain unclear. Long non-coding RNA (lncRNA), modulates DNA/RNA/proteins at epigenetic, pre-transcriptional, transcriptional and posttranscriptional levels, and plays a potential therapeutic role in various diseases. This study aims to identify lncRNAs that have a potential impact on GS-promoted GBC progression.Six GBC patients without GS, six normal gallbladder tissues, nine gallstones and nine GBC patients with GS were admitted to our hospital. The next-generation RNA-sequencing was performed to analyze differentially expressed (DE) lncRNA and messenger RNA (mRNA) in four groups. Then overlapping and specific molecular signatures were analyzed. We identified 29 co-DEGs and 500 co-DElncRNAs related to gallstone or GBC. The intersection and concatenation of co-DEGs and co-DElncRNA functionally involved in focal adhesion, Transcriptional misregulation in cancers, Protein digestion and absorption, and ECM-receptor interaction signaling pathways may contribute to the development of gallbladder cancer. Further exploration is necessary for early diagnosis and the potential treatment of GBC. FXYD2, MPZL1 and PAH were observed in both co-DEGs and co-DElncRNA and validated by qRT-PCR.Our data identified a series of DEGs and DElncRNAs, which were involved in the progression of GBC and GS-related metabolism pathways. Compared to GBC, the GS profile was more similar to para-tumor tissues in transcriptome level and lower risk of cancer. Further exploration is necessary from GBC patients with different periods of follow-up gallstone.© 2024 Wang et al.