Abstract
Gallbladder carcinoma (GBC) is a rare tumor with a dismal survival rate overall. Hence, there is an urgent need for exploring more specific and sensitive biomarkers for the diagnosis and treatment of GBC. At first, amplified total RNAs from two paired GBC tumors and adjacent non-tumorous tissues (ANTTs) were subjected to RNA sequencing. 161 genes were identified differentially expressed between tumors and ANTTs. Functional enrichment analysis indicated that the up-regulated genes in tumor were primarily associated with signaling molecules and enzyme modulators, and mainly involved in cell cycles and pathways in cancer. Twelve differentially expressed genes (DEGs) were further confirmed in another independent cohort of 35 GBC patients. Expression levels of BIRC5, TK1, TNNT1 and MMP9 were found to be positively related to postoperative relapse. There was also a significant correlation between BIRC5 expression and tumor-node-metastasis (TNM) stage. Besides, we observed a positive correlation between serum CA19-9 concentration and the expression levels of TNNT1, MMP9 and CLIC3. Survival analysis revealed that GBC patients with high TK1 and MMP9 expression levels had worse prognosis. These identified DEGs might not only be promising biomarkers for GBC diagnosis and prognosis, but also expedite the discovery of novel therapeutic strategies.
Highlights
Gallbladder carcinoma (GBC), as the fifth most common gastrointestinal cancer, is a relatively uncommon but challenging cancer
There was no significant difference between numbers of genes detected in each pair of tumor and adjacent non-tumorous tissues (ANTTs)
The evaluations of sequencing randomness and saturation proved the RNA sequencing (RNA-Seq) system is good in quality
Summary
Gallbladder carcinoma (GBC), as the fifth most common gastrointestinal cancer, is a relatively uncommon but challenging cancer. In these years its incidence is increasing in China [1]. GBC is the most common cause of mortality among biliary tract cancers (BCTs). The median survival time for individuals with GBC is no more than one year [2]. In spite of multiple studies on novel molecules for diagnosis and prediction of clinical outcomes in GBC [6], the progress in clinical applications has so far been limited. More precise markers with better sensitivity and specificity for GBC are needed to benefit the patients and expedite the discovery of novel therapeutic strategies
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