RNA sequencing reveals differentially expressed genes as potential diagnostic and prognostic indicators of gallbladder carcinoma
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Xing Gu1,*, Bin Li2,*, Mingming Jiang1, Meng Fang1, Jun Ji1, Aihua Wang1, Mengmeng Wang1, Xiaoqing Jiang2, Chunfang Gao1
1Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China
2Department of Biliary Tract Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, PR China
*These authors have contributed equally to this work
Chunfang Gao, e-mail: [email protected]
Xiaoqing Jiang, e-mail: [email protected]
Keywords: biomarker, oncology, oncogene, tumor suppressor, tumorgenesis
Received: February 25, 2015 Accepted: April 14, 2015 Published: April 28, 2015
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.
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