Exploration of differentially-expressed exosomal mRNAs, lncRNAs and circRNAs from serum samples of gallbladder cancer and xantho-granulomatous cholecystitis patients

Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Although a growing number of studies have explored the mechanism of GBC, thus far, few molecules have been discovered that can be utilized as specific biomarkers for the early diagnosis and therapeutic treatment of GBC. Recent studies have shown that exosomes not only participate in the progression of tumors, but also carry specific information that can define multiple cancer types. The present study investigated the expression profiles of coding (or messenger) ribonucleic acids (mRNAs) and non-coding RNAs (ncRNAs, including long non-coding RNAs [lncRNAs] and circular RNAs [circRNAs]) in plasma-derived exosomes from GBC patients. Using high-throughput RNA sequencing and subsequent bioinformatic analysis, a number of differentially expressed (DE) mRNAs, lncRNAs, and circRNAs were identified in GBC exosomes, compared to their expressions in xantho-granulomatous cholecystitis (XGC) exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were then conducted to investigate the potential functions of these DE RNAs. Furthermore, the interaction networks and competing endogenous RNA networks of these DE RNAs and their target genes were investigated, revealing a complex regulatory network among mRNAs and ncRNAs. In summary, this study demonstrates the diagnostic value of plasma-derived exosomes in GBC and provides a new perspective on the mechanism of GBC.

胆囊癌（GBC）是全球范围内最常见的胆道恶性肿瘤。尽管已有越来越多的研究对胆囊癌的发病机制展开探索，但截至目前，可用于胆囊癌早期诊断与治疗的特异性生物标志物仍屈指可数。现有研究表明，外泌体（exosomes）不仅参与肿瘤的发生与发展进程，还携带可区分多种癌症类型的特异性信息。本研究对胆囊癌患者血浆来源外泌体中的编码RNA（即信使RNA，mRNAs）与非编码RNA（ncRNAs，包括长链非编码RNA [lncRNAs] 和环状RNA [circRNAs]）的表达谱进行了分析。通过高通量RNA测序及后续生物信息学分析，本研究对比了胆囊癌外泌体与黄色肉芽肿性胆囊炎（XGC）外泌体的RNA表达水平，鉴定出一批差异表达（DE）的mRNAs、lncRNAs及circRNAs。随后通过基因本体论（GO）与京都基因与基因组百科全书（KEGG）富集分析，探究了这些差异表达RNA的潜在功能。此外，本研究还分析了这些差异表达RNA及其靶基因的相互作用网络与内源竞争RNA网络，揭示了mRNAs与ncRNAs之间复杂的调控网络。综上，本研究证实了血浆来源外泌体在胆囊癌诊断中的应用价值，同时为胆囊癌发病机制的研究提供了全新视角。